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WO2024126404A1 - Imidazo[1,2-a]pyridine derivatives - Google Patents

Imidazo[1,2-a]pyridine derivatives Download PDF

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Publication number
WO2024126404A1
WO2024126404A1 PCT/EP2023/085190 EP2023085190W WO2024126404A1 WO 2024126404 A1 WO2024126404 A1 WO 2024126404A1 EP 2023085190 W EP2023085190 W EP 2023085190W WO 2024126404 A1 WO2024126404 A1 WO 2024126404A1
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Prior art keywords
6alkyl
6alkoxy
formula
attachment
groups
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PCT/EP2023/085190
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French (fr)
Inventor
Christopher Charles SCARBOROUGH
Martin Pouliot
Peter FINKBEINER
Damien BONVALOT
Nicolas Germain
Stephane André Marie JEANMART
Camille LE CHAPELAIN
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Syngenta Crop Protection Ag
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Publication of WO2024126404A1 publication Critical patent/WO2024126404A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/20—N-Aryl derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides

Definitions

  • Imidazo[1,2-a]pyridine derivatives The present invention relates to microbiocidal imidazo[1,2-a]pyridine derivatives, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity, more particularly activity against oomycetes.
  • the invention also relates to preparation of these imidazo[1,2-a]pyridine derivatives, to intermediates useful in the preparation of these imidazo[1,2-a]pyridine derivatives, to the preparation of these intermediates, to agrochemical compositions which comprise at least one of the imidazo[1,2- a]pyridine derivatives, to preparation of these compositions and to the use of the imidazo[1,2-a]pyridine derivatives or compositions in agriculture or horticulture for combating, controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, in particular fungi, more particularly oomycetes.
  • the present invention provides compounds of formula (I) 2b a 5-8-membered heterocycle, a 6-12-membered aromatic ring or a 5-11-membered heteroaromatic ring, wherein each of the 5-8-membered carbocycle, the 5-8-membered heterocycle, the 6-12-membered aromatic ring or the 5-11-membered heteroaromatic ring is optionally substituted with one to four substituents independently selected from R 1 ;
  • A is CH or N;
  • a 1 is a carbon or nitrogen atom;
  • a 2 is a carbon or nitrogen atom;
  • a 3 are independently CR 4 or N, with the proviso that no more than four A 3 are N, preferably no more than three A 3 are N, preferably no more than two A 3 are N, preferably no more than one A 3 is N, and more
  • R 2a , R 2b and R 2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy;
  • R 4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl
  • the present invention provides an agrochemical composition comprising a compound of formula (I), and more particularly an agrochemical composition comprising a fungicidally effective amount of a compound of formula (I).
  • Said composition can further comprise at least one compound selected among an additional active ingredient, an appropriate formulation inert, a carrier, an adjuvant, and any mixtures thereof.
  • Compounds of formula (I) may be used to control phytopathogenic microorganisms.
  • a compound of formula (I), or a composition comprising a compound of formula (I) according to the invention may be applied directly to the phytopathogen, to the locus of a phytopathogen, in particular to a plant susceptible to attack by phytopathogens, or to a propagation material of a plant.
  • the present invention provides the use of a compound of formula (I), or a composition comprising a compound of formula (I), as described herein to combat, prevent or control a phytopathogen.
  • the present invention provides a method of combating, preventing or controlling phytopathogens, comprising applying a compound of formula (I), or a composition comprising a compound of formula (I), as described herein to said phytopathogen, to the locus of said phytopathogen, in particular to a plant susceptible to attack by a phytopathogen, or to a propagation material of a plant.
  • Compounds of formula (I) are particularly effective in combating, preventing or controlling phytopathogenic fungi, in particular oomycetes.
  • the present invention provides the use of a compound of formula (I), or a composition comprising a compound of formula (I), as described herein to control phytopathogenic fungi, in particular oomycetes.
  • the present invention provides a method of combating, preventing or controlling phytopathogenic disease, such as phytopathogenic fungi, comprising applying a compound of formula (I), or a composition comprising a compound of formula (I), as described herein to said phytopathogenic fungi, or to the locus of said phytopathogenic fungi, in particular to a plant susceptible to attack by phytopathogenic fungi, in particular oomycetes, or to a propagation material of a plant.
  • a group is indicated as being substituted, e.g. alkyl, this includes those groups that are part of other groups, e.g. the alkyl in alkylthio.
  • halogen refers to fluorine (fluoro or F), chlorine (chloro or Cl), bromine (bromo or Br) or iodine (iodo or I), preferably fluorine, chlorine or bromine.
  • Alkyl as used herein- in isolation or as part of a chemical group – represents straight-chain or branched hydrocarbons, preferably with 1 to 6 carbon atoms, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, 1- methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2- dimethylpropyl, 1,1 -dimethylpropyl, 2,2- dimethylpropyl, 1 -ethylpropyl, hexyl, 1 -methylpentyl, 2- methylpentyl, 3-methylpentyl, 4- methylpentyl, 1,2-dimethylpropyl, 1,3-dimethylbutyl, 1,4-dimethylbutyl, 2,3-dimethylbutyl, 1,1- dimethylbutyl, 2,2-dimethylbut
  • Alkyl groups with 1 to 4 carbon atoms are preferred, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl or t-butyl.
  • Alkenyl in isolation or as part of a chemical group - represents straight-chain or branched hydrocarbons, preferably with 2 to 6 carbon atoms and at least one double bond, for example vinyl, 2- propenyl, 2-butenyl, 3-butenyl, 1- methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl, 4- pentenyl, 1-methyl-2-butenyl, 2- methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3- butenyl, 3-methyl-3-butenyl, 1,1 - dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 1 -ethyl-2-propenyl, 2- hexenyl, 3-hexenyl, 4- hexenyl, 5-hexenyl, 1 -methyl-2-pentenyl, 2-methyl-2-pentenyl, 2-methyl-2-penten
  • Alkenyl groups with 2 to 4 carbon atoms are preferred, for example 2-propenyl, 2-butenyl or 1-methyl-2-propenyl.
  • the term "Alkynyl" - in isolation or as part of a chemical group - represents straight-chain or branched hydrocarbons, preferably with 2 to 6 carbon atoms and at least one triple bond, for example 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2- propynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-3-butynyl, 2- methyl-3-butynyl, 1-methyl-2- butynyl, 1,1 -dimethyl-2-propynyl, 1 -ethyl-2-propynyl, 2-hexynyl, 3- hexynyl, 4-hexynyl, 5-hexynyl, 1- methyl-2-pentyn
  • Alkynyls with 2 to 4 carbon atoms are preferred, for example ethynyl, 2- propynyl or 2-butynyl-2-propenyl.
  • cycloalkyl in isolation or as part of a chemical group - represents saturated or partially unsaturated mono-, bi- or tricyclic hydrocarbons, preferably with 3 to 10 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl or adamantyl.
  • alkoxy refers to a radical of the formula -ORa wherein Ra is an alkyl radical as generally defined above. Examples of alkoxy include, but are not limited to methoxy, ethoxy, propoxy, iso-propoxy, and tert-butoxy.
  • alkylsulfanyl refers to a radical of the formula -SRa wherein Ra is an alkyl radical as generally defined above.
  • alkylsulfinyl refers to a radical of the formula -S(O)Ra wherein Ra is an alkyl radical as generally defined above.
  • alkylsulfonyl refers to a radical of the formula -S(O)2Ra wherein Ra is an alkyl radical as generally defined above.
  • alkoxycarbonyl refers to a radical of the formula RaOC(O)-, wherein Ra is an alkyl radical as generally defined above.
  • alkylaminocarbonyl refers to a radical of the formula RaNHC(O)- wherein Ra is an alkyl radical as generally defined above.
  • - Hydroxyl or hydroxy stands for a –OH group.
  • the term "effective amount” refers to the amount of the compound, a salt, or N-oxide thereof, which, upon single or multiple applications provides the desired effect. An effective amount is readily determined by the skilled person in the art, by the use of known techniques and by observing results obtained under analogous circumstances.
  • Compounds of formula (I) which have at least one basic centre can form, for example, acid addition salts, for example with strong inorganic acids such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as C1-C4alkanecarboxylic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid,
  • Compounds of formula (I) which have at least one acidic group can form, for example, salts with bases, for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine.
  • bases for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts
  • salts with ammonia or an organic amine such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower-alkylamine, for example ethyl-, die
  • the compounds of formula (I) according to the invention are in free form, in oxidized form as an N-oxide, in covalently hydrated form, or in salt form, e.g., an agronomically usable or agrochemically acceptable salt form.
  • N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.
  • the compounds of formula (I) according to the invention also include hydrates, which may be formed during salt formation.
  • the compounds of formula (I) according to the invention also include hydrates which may be formed during the salt formation.
  • a compound of formula (I) according to the present invention wherein four A 3 are CR 4 and one A 3 is N.
  • a compound of formula (I) according to the present invention wherein , and preferably the four A 3 are CR 4 .
  • a compound of formula (I) according to the present invention wherein 3 , and preferably the four A 3 are CR 4 .
  • a compound of formula (I) according to the present invention wherein A 1 is a carbon atom and A 2 is a nitrogen atom. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein A 1 is a carbon atom and A 2 is a carbon atom. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein A 1 is a nitrogen atom and A 2 is a carbon atom. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein A 1 is a nitrogen atom and A 2 is a nitrogen atom.
  • a compound of formula (I) wherein ring W * selected from: , , group , the point of attachment to the ring formed by the A 3 groups, and wherein R 11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1- 4alkyl, C2-6alkenyl and C2-6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN.
  • Ring W can be optionally substituted with one to four substituents independently selected from R 1 as defined in the present invention. More preferably, ring W * wherein * represents the point of attachment to the imidazopyridine group in formula (I), and # represents the point of attachment to the ring formed by the A 3 groups, and wherein R 11 is as defined in the present invention. Ring W can be optionally substituted with one to four substituents independently selected from R 1 as defined in the present invention.
  • a compound of formula (I) wherein ring W is a 5-8-membered heterocycle or a 5-11-membered heteroaromatic ring, wherein each of the 5- 8-membered heterocycle or the 5-11-membered heteroaromatic ring is optionally substituted with one to four substituents independently selected from R 1 ,
  • a 1 is a carbon or nitrogen atom;
  • a 2 is a carbon or nitrogen atom; * and more preferably selected from: wherein * represents the point of attachment to the imidazopyridine group in formula (I), and # represents the point of attachment to the ring formed by the A 3 groups, ring W being optionally substituted with one to four substituents independently selected from R 1 as defined in the present invention, and wherein R 11 is as defined in the present invention;
  • A is N;
  • a 3 are independently CR 4 or N, with the proviso that no more than three A 3 are N, preferably no more than two A 3 are N, preferably no more than
  • the compound according to the present invention is selected from: methyl N-[5-[6-[4-(4-fluorophenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate; methyl N-[5-[8-cyclopropyl-6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate;
  • the method according to the present invention has advantageous properties for protecting plants against pathogenic, such as phytopathogenic, especially fungi such as oomycetes, attack or infestation, which result in a disease and damage to the plant; particularly in instance of plants, the present invention can control, limit or prevent pathogenic damage on plant, parts of plant, plant propagation material and/or plant grown.
  • pathogenic such as phytopathogenic, especially fungi such as oomycetes, attack or infestation
  • the present invention can control, limit or prevent pathogenic damage on plant, parts of plant, plant propagation material and/or plant grown.
  • Table 1.1 provides compounds E1.1 to E1.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Tables 1.2 to 1.162 discloses individual compounds of the formula (I- 1) in which A, R 2a , R 2c , R 6 and ring W are specifically defined in Tables 1.2 to 1.162, which refer to Table Z wherein A 3a , A 3b , R 2b , R 4 are specifically defined.
  • Table 1.3 provides compounds E3.1 to E3.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 * * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.4 provides compounds E4.1 to E4.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 * * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.5 provides compounds E5.1 to E5.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 * * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.6 provides compounds E6.1 to E6.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 , wherein * represents the point of attachment to the , # represents the point of attachment to the ring formed by the A 3 groups,and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.7 provides compounds E7.1 to E7.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 , wherein * represents the point of attachment to the , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.8 provides compounds E8.1 to E8.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 * * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.9 provides compounds E9.1 to E9.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 * , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.10 provides compounds E10.1 to E10.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.11 provides compounds E11.1 to E11.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.12 provides compounds E12.1 to E12.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.13 provides compounds E13.1 to E13.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.14 provides compounds E14.1 to E14.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.15 provides compounds 1.15.1 to E15.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.16 provides compounds E16.1 to E16.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.17 provides compounds E17.1 to E17.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.18 provides compounds E18.1 to E18.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.19 provides compounds E19.1 to E19.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.20 provides compounds E20.1 to E20.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.21 provides compounds E21.1 to E21.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.22 provides compounds E22.1 to E22.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.23 provides compounds E23.1 to E23.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.24 provides compounds E24.1 to E24.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.25 provides compounds E25.1 to E25.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.26 provides compounds E26.1 to E26.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.27 provides compounds E27.1 to E27.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.28 provides compounds E28.1 to * 1), and # represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.29 provides compounds E29.1 to E29.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.30 provides compounds E30.1 to 1.30.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.31 provides compounds E31.1 to E31.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.32 provides compounds E32.1 to E32.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.33 provides compounds E33.1 to E33.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.34 provides compounds E34.1 to E34.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.35 provides compounds E35.1 to E35.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.36 provides compounds E36.1 to E36.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.37 provides compounds E37.1 to E37.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.38 provides compounds E38.1 to E38.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.39 provides compounds E39.1 to E39.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.40 provides compounds E40.1 to E40.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.41 provides compounds E41.1 to E41.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.42 provides compounds E42.1 to E42.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.43 provides compounds E43.1 to E43.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.44 provides compounds E44.1 to E44.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.45 provides compounds E45.1 to E45.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.46 provides compounds E46.1 to E46.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.47 provides compounds E47.1 to E47.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.48 provides compounds E48.1 to E48.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.49 provides compounds E49.1 to E49.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.50 provides compounds E50.1 to E50.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.51 provides compounds E51.1 to E51.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.52 provides compounds E52.1 to E52.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.53 provides compounds E53.1 to E53.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.54 provides compounds E54.1 to E54.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.55 provides compounds E55.1 to E55.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.56 provides compounds E56.1 to E56.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is , , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.57 provides compounds E57.1 to E57.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.58 provides compounds E58.1 to E58.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.59 provides compounds E59.1 to E59.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.60 provides compounds E60.1 to E60.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.61 provides compounds E61.1 to E61.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.62 provides compounds E62.1 to E62.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.63 provides compounds E63.1 to E63.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.64 provides compounds E64.1 to E64.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.65 provides compounds E65.1 to E65.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.66 provides compounds E66.1 to E66.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.69 provides compounds E69.1 to E69.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.70 provides compounds E70.1 to E70.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.71 provides compounds E71.1 to E71.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.72 provides compounds E72.1 to E72.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.73 provides compounds E73.1 to E73.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.74 provides compounds E74.1 to E74.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * # , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.75 provides compounds E75.1 to E75.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.76 provides compounds E76.1 to E76.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.77 provides compounds E77.1 to E77.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.78 provides compounds E78.1 to E78.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.79 provides compounds E79.1 to E79.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.80 provides compounds E80.1 to E80.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.81 provides compounds E81.1 to E81.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.82 provides compounds E82.1 to E82.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.83 provides compounds E83.1 to E83.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH 3 , , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.84 provides compounds E84.1 to E84.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.85 provides compounds E85.1 to E85.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH 3 , , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.86 provides compounds E86.1 to E86.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.87 provides compounds E87.1 to E87.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.89 provides compounds E89.1 to E89.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.90 provides compounds E90.1 to E90.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.91 provides compounds E91.1 to E91.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.92 provides compounds E92.1 to E92.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.93 provides compounds E93.1 to E93.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.94 provides compounds E94.1 to E94.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.95 provides compounds E95.1 to E95.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.96 provides compounds E96.1 to E96.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.97 provides compounds E97.1 to E97.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.98 provides compounds E98.1 to E98.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, * R 6 is CH3, , wherein * represents the point of attachment to the group , represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.99 provides compounds E99.1 to E99.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.100 provides compounds E100.1 to E100.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.101 provides compounds E101.1 to E101.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.102 provides compounds E102.1 to E102.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.103 provides compounds E103.1 to E103.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.105 provides compounds E105.1 to E105.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1106 provides compounds E106.1 to E106.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.108 provides compounds E108.1 to E108.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.109 provides compounds E109.1 to E109.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.110 provides compounds E110.1 to E110.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.111 provides compounds E111.1 to E111.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.112 provides compounds E112.1 to E112.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.113 provides compounds E113.1 to E113.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.114 provides compounds E114.1 to E114.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.115 provides compounds E115.1 to E115.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, rin , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.116 provides compounds E116.1 to E116.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1117 provides compounds E117.1 to E117.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.118 provides compounds E118.1 to E118.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.119 provides compounds E119.1 to E119.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.120 provides compounds E120.1 to E120.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.121 provides compounds E121.1 to E121.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.122 provides compounds E122.1 to E122.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.123 provides compounds E123.1 to E123.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.124 provides compounds E124.1 to E124.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * W H, R 6 is OCH3, ring W # is , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.125 provides compounds E125.1 to E125.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.126 provides compounds E126.1 to E126.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.127 provides compounds E127.1 to E127.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.128 provides compounds E128.1 to E128.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is H, R 6 is OCH 3 , , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1129 provides compounds E129.1 to E129.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.130 provides compounds E130.1 to E130.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.131 provides compounds E131.1 to E131.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.132 provides compounds E132.1 to E132.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1133 provides compounds E133.1 to E133.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is OCH3, , wherein * represents the point of attachment to the group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.134 provides compounds E134.1 to E134.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c * is H, R 6 is CH3, , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.135 provides compounds E135.1 to E135.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.136 provides compounds E136.1 to E136.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is , , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.137 provides compounds E137.1 to E137.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is , , wherein * represents the point of attachment to the group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.138 provides compounds E138.1 to E138.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is , , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.139 provides compounds E139.1 to E139.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.140 provides compounds E140.1 to E140.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.141 provides compounds E141.1 to E141.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.142 provides compounds E142.1 to E142.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.143 provides compounds E143.1 to E143.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.144 provides compounds E144.1 to E144.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.145 provides compounds E145.1 to E145.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.146 provides compounds E146.1 to E146.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.147 provides compounds E147.1 to E147.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.148 provides compounds E148.1 to E148.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.149 provides compounds E149.1 to E149.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.150 provides compounds E150.1 to E150.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.151 provides compounds E151.1 to E151.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * W H, R 6 is , ring W # is , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.152 provides compounds E152.1 to E152.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.153 provides compounds E153.1 to E153.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.154 provides compounds E154.1 to E154.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.155 provides compounds E155.1 to E155.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.156 provides compounds E156.1 to E156.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is , , wherein * represents the point of attachment to the , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.157 provides compounds E157.1 to E157.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is , , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.158 provides compounds E158.1 to E158.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is , , wherein * represents the point of attachment to the group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1159 provides compounds E159.1 to E159.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is , , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.160 provides compounds E160.1 to E160.1078 of formula (I-1) wherein A is N, R 2a is H, R 2c is * H, R 6 is , , wherein * represents the point of attachment to the imidazopyridine group , the point of attachment to the ring formed by the A 3 groups, A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.161 provides compounds E161.1 to E161.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c * is H, R 6 is CH3, , wherein * represents the point of attachment to fthe , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Table 1.162 provides compounds E162.1 to E162.1078 of formula (I-1) wherein A is CH, R 2a is H, R 2c is H, R 6 is CH3, , wherein * represents the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A 3 groups, and A 3a , A 3b , R 2b , R 4 are as defined in table Z.
  • Compounds according to the invention may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile, improved physico-chemical properties, or increased biodegradability).
  • Compounds according to the invention have particularly advantageous levels of biological activity for protecting plants against oomycetes such as Phytophthora, Plasmopara and Pythium.
  • Compounds of formula (I) according to the invention can be made as shown in the following schemes 1 to 22, in which, unless otherwise stated, the definition of each variable is as defined in the present invention.
  • Compounds of formula (I) can be prepared via Suzuki cross coupling of compounds of formula (II), wherein X is Cl, Br or I, and a compound of formula (III), wherein either R 8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R 8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate, chloro(2- dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II
  • compounds of formula (Va), wherein X is Cl, Br, I or a triflate group can be prepared by the reaction of a compound of formula (VIIa) with triflic anhydride and, optionally, a base, such as triethylamine or pyridine, or a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide, or by successive reaction with phosphorus oxychloride and sodium iodide.
  • bases such as triethylamine or pyridine
  • a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide
  • These transformations are performed neat or in a suitable solvent such as dichloromethane, toluene or xylene. These transformations are depicted in Scheme 3.
  • Compounds of formula (IV) wherein X is Cl, Br or I, and wherein X is more preferably Cl, and wherein either R 8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R 8 together can form a C3-C8 cycloalkyl can be prepared by the reaction of a compound of formula (VIII) with a halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide in a suitable solvent, such as DMF, acetonitrile, dichloromethane or tetrahydrofuran. This transformation is depicted in Scheme 4.
  • a halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide
  • Alternatively compounds of formula (VIII) wherein either R 8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R 8 together can form a C3-C8 cycloalkyl can be prepared by the reaction of a compound of formula (IX), wherein X is Cl, Br or I, with a compounds of formula (XI) wherein either R 8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R 8 together can form a C3-C8 cycloalkyl, such as trimethyl borate, triisopropyl borate, isopropoxy 4,4,5,5-tetramethyl-1,3,2- dioxaborolane, or 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, and a metal halogen exchange reagent, such as butyl lithium or ethylmagnesium bromide, in a suitable solvent, such as tetrahydrofuran, diethyl ether or di
  • the outcome of the reaction can be improved by using a base, such as sodium bicarbonate or potassium carbonate, or by using an acid, such as p-toluenesulfonic acid or hydrogen bromide.
  • a base such as sodium bicarbonate or potassium carbonate
  • an acid such as p-toluenesulfonic acid or hydrogen bromide.
  • compounds of formula (II), wherein X is Cl, Br or I, and wherein X is more preferably Cl can be prepared by the reaction of a compound of formula (XV), with a halogenating agent such as N- chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide in a suitable solvent, such as DMF, acetonitrile, dichloromethane or tetrahydrofuran.
  • a halogenating agent such as N- chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide in a suitable solvent, such as DMF, acetonitrile, dichloromethane or tetrahydrofuran.
  • compounds of formula (IIa), wherein A 1 is a carbon atom in formula (II) wherein X is Cl, Br or I, and wherein X is more preferably Cl can be prepared by the reaction of a compound of formula (XVIII), wherein either X is independently from each other Cl, Br or I, with a compounds of formula (XIXa) wherein either R 8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R 8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chlor
  • Compounds of formula (XXIId), wherein A 1 and A 2 are carbon atoms in formula (XXII), and wherein X is Cl, Br or I, can be prepared via Suzuki cross coupling of compounds of formula (XXIIId), wherein either R 8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R 8 together can form a C3-C8 cycloalkyl, and a compound of formula (XVIII), wherein either X independently is Cl, Br or I, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent
  • Compounds of formula (XVc), wherein A 1 is a nitrogen atom in formula (XV), can be prepared by the reaction of a compound of formula (IX), wherein X is Cl, Br or I, with a compound of formula (XXIVc), wherein A 1 is a nitrogen atom in formula (XXIV) in the presence of a base, such as Cs2CO3, K2CO3, K2HPO4 or NaOtBu, and a suitable palladium catalyst, and a suitable palladium catalyst, such as XPhos Pd G3, t-BuXPhos Pd G3, Me3tBuXPhos Pd G3, JohnPhos Pd G3, RuPhos Pd G3, BrettPhos Pd G3 or tBuBrettPhos Pd G3, in a suitable solvent, such as dimethylformamide, dimethylacetamide, dioxane, tetrahydrofuran or toluene.
  • a base such as Cs2CO3, K2CO3, K
  • compounds of formula (XVc), wherein A 1 is a nitrogen atom in formula (XV) can be prepared by the reaction of a compound of formula (VIII), wherein either R 8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R 8 together can form a C3-C8 cycloalkyl, with a compound of formula (XXIVc) in the presence of a base, such as triethylamine, diisopropylethylamine, pyridine, Cs2CO3, K2CO3, K2HPO4 or NaOtBu, and a suitable catalyst, such as copper(II) acetate, copper(II) carbonate, copper(II) hydroxide, copper oxide, copper(I) iodide or copper(I) bromide, in a suitable solvent, such as dimethylformamide, dimethylacetamide, dioxane, acetonitrile, tetrahydrofuran or
  • the outcome of the reaction can be improved by adding boric acid or molecular sieves to the reaction mixture. It is understood that these transformations are done under air as oxygen is needed as a terminal oxidant. In some cases, the copper species might be used in stochiometric amount. This transformation is depicted in Scheme 18.
  • the person skilled in the art would also recognize that the compounds of formula (I) can alternatively be prepared by the de novo construction of the ring W. Such synthetic routes have been used and are described in the experimental section of the present invention. It is understood by the person skilled in the art that the synthetic routes describing the access to those specific compounds can also be used to synthesize analogous compounds of formula (I) of this specific compound, wherein said compounds have identical ring W.
  • This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is a pyrazole (compounds of formula (I- a)) as well as the synthesis of compounds of formula (II), wherein W is a pyrazole and X is Cl, Br or I (compounds of formula (II-a)).
  • This methodology can be used in general terms to access analogous compounds of formula (I-a) and formula (II-a).
  • (I-a) (II-a)
  • the below compounds of formula (I-b) and (II-b) can be prepared following the synthetic route used in the example 29.
  • the example 29 describes the preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 75).
  • This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is a triazole (compounds of formula (I-b)) as well as the synthesis of compounds of formula (II), wherein W is a triazole and X is Cl, Br or I (compounds of formula (II-b)).
  • This methodology can be used in general terms to access analogous compounds of formula (I-b) and formula (II-b).
  • the below compounds of formula (I-c) and (II-c) can be prepared following the synthetic route used in the examples 25, 27 and 28.
  • the example 28 describes the preparation of methyl N-[5-[6-[2-(4-fluoro- 3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]80yridine-3-yl]-2-pyridyl]carbamate (compound 4)
  • the example 27 describes the preparation of methyl N-[5-[6-[5-cyano-2-(4-fluorophenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]80yridine-3-yl]-2-pyridyl]carbamate (compound 74)
  • the example 25 describes the preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]imi
  • the example 9 describes the preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy- phenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 10).
  • This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is an oxadiazine (compounds of formula (I-d)) as well as the synthesis of compounds of formula (II), wherein W is an oxadiazine and X is Cl, Br or I (compounds of formula (II-d)).
  • This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is an oxadiazolone (compounds of formula (I-e)) as well as the synthesis of compounds of formula (II), wherein W is an oxadiazolone and X is Cl, Br or I (compounds of formula (II-e)).
  • This methodology can be used in general terms to access analogous compounds of formula (I-e) and formula (II-e).
  • the below compounds of formula (I-f) and (II-f) can be prepared following the synthetic route used in the example 38.
  • the example 38 describes the preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy- phenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 9).
  • This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is a triazole (compounds of formula (I-f)) as well as the synthesis of compounds of formula (II), wherein W is a triazole and X is Cl, Br or I (compounds of formula (II-f)).
  • This methodology can be used in general terms to access analogous compounds of formula (I-f) and formula (II-f).
  • 2b 2b (I-f) (II-f) The below compounds of formula (I-g) and (II-g) can be prepared following the synthetic route used in the example 35.
  • the example 35 describes the preparation of methyl N-[5-[6-[1-(4-fluoro-3-methoxy- phenyl)imidazol-2-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 8).
  • This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is an imidazole (compounds of formula (I-g)) as well as the synthesis of compounds of formula (II), wherein W is an imidazole and X is Cl, Br or I (compounds of formula (II-g)).
  • This methodology can be used in general terms to access analogous compounds of formula (I-h) and formula (II-h).
  • these de novo synthesis might require using compounds of formula (XVI), wherein X is Cl, Br or I, and R 9 is hydrogen or C1-C6 alkyl, or the use of compound of formula (XVII), wherein R9 is hydrogen or C1-C6 alkyl.
  • compounds of formula (XVII), wherein R 9 is hydrogen or C1-C6 alkyl can be prepared by the reaction of a compound of formula (XXV), wherein R 9 is hydrogen or C1-C6 alkyl, and a compound of formula (XIII), wherein X is Cl, Br or I, or its corresponding acetal of formula (XIV), wherein X is Cl, Br or I and either R 10 is independently from each other C1-C6 alkyl or wherein two R 10 together can form a C3-C8 cycloalkyl, in a solvent, such as water, ethanol, acetone or acetonitrile.
  • a solvent such as water, ethanol, acetone or acetonitrile.
  • the outcome of the reaction can be improved by using a base, such as sodium bicarbonate or potassium carbonate, or by using an acid, such as p-toluenesulfonic acid or hydrogen bromide.
  • a base such as sodium bicarbonate or potassium carbonate
  • an acid such as p-toluenesulfonic acid or hydrogen bromide.
  • Compounds of formula (XXV), wherein R 9 is hydrogen or C1-C6 alkyl are prepared by known methods or are commercially available. This transformation is depicted in Scheme 21.
  • compounds of formula (I) can be obtained by acylation of compounds of formula (XXVI) using an acylation reagent of formula (XXVII), wherein X is Cl or Br, in the presence of a base such as triethylamine, pyridine or potassium carbonate.
  • Compounds of formula (XXVI) can be prepared via Suzuki cross coupling of compounds of formula (II), wherein X is Cl, Br or I, and a compound of formula (XXVIII), wherein either R 8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate, chloro(2- dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]pal
  • the term “compound/compounds according to the invention” refers to compounds according to the present invention.
  • the compounds according to the present invention can be obtained by using standard synthesis techniques known to the person skilled in the art. Non-exhaustive examples include oxidation reactions, reduction reactions, hydrolysis reactions, coupling reactions, aromatic nucleophilic or electrophilic substitution reactions, nucleophilic substitution reactions, nucleophilic addition reactions, olefination reactions, oxime formation, alkylation and halogenation reactions.
  • a compound according to the present invention can be converted in a manner known per se into another compound according to the present invention by replacing one or more substituents of the starting compound according to the present invention in the customary manner by (an)other substituent(s) according to the invention.
  • Salts of the compounds according to the present invention can be prepared in a manner known per se.
  • acid addition salts of the compounds according to the present invention are obtained by treatment with a suitable acid or a suitable ion exchanger reagent and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent.
  • Salts of compounds the compounds according to the present invention can be converted in the customary manner into the free compounds, acid addition salts, for example, by treatment with a suitable basic compound or with a suitable ion exchanger reagent and salts with bases, for example, by treatment with a suitable acid or with a suitable ion exchanger reagent.
  • Salts of the compounds according to the present invention can be converted in a manner known per se into other salts of the compounds according to the present invention, acid addition salts, for example, into other acid addition salts, for example by treatment of a salt of inorganic acid such as hydrochloride with a suitable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture.
  • a salt of inorganic acid such as hydrochloride
  • a suitable metal salt such as a sodium, barium or silver salt
  • an acid for example with silver acetate
  • a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture.
  • the compounds according to the present invention, which have salt-forming properties can be obtained in free form or in the form of salts.
  • the compounds according to the present invention and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can be present in the form of one of the stereoisomers which are possible or as a mixture of these, for example in the form of pure stereoisomers, such as antipodes and/or diastereomers, or as stereoisomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure stereoisomers and also to all stereoisomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case.
  • Diastereomer mixtures or racemate mixtures of the compounds according to the present invention in free form or in salt form, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.
  • Enantiomer mixtures such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl celulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the
  • N-oxides can be prepared by reacting a compound according to the present invention with a suitable oxidizing agent, for example the H2O2/urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride.
  • a suitable oxidizing agent for example the H2O2/urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride.
  • a compound of formula (II) ; group (II), and # represents the point of attachment to the ring formed by the A 3 groups, and wherein R 11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2- 6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A 1 is a carbon or nitrogen atom; A 2 is a carbon or nitrogen atom; A 3 are independently CR 4 or N, with the proviso that no more than four A 3 are N, preferably no more than three A 3 are N, preferably no more than two A 3
  • R 2a , R 2b and R 2c are independently selected from hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy-C 1-6 alkyl, C 3-6 cycloalkyl-C 1- 4alkyl, and C1-6alkoxy;
  • R 4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alk
  • R 2a , R 2b and R 2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and R 4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl,
  • a compound of formula (XXVI) wherein * represents the point of attachment to the imidazopyridine group in formula (XXVI), and # represents the point of attachment to the ring formed by the A 3 groups, and wherein R 11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2- 6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A is CH or N; A 1 is a carbon or nitrogen atom; A 2 is a carbon or nitrogen atom; A 3 are independently CR 4 or N, with the proviso that no more than four
  • R 2a , R 2b and R 2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and R 4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6 alkoxy, halogen, CN, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-6 alkyl, C 1-6 alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6al
  • a 1 is a carbon or nitrogen atom;
  • R 2a , R 2b and R 2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3-
  • R 2a , R 2b and R 2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and X is Cl, Br or I.
  • R 2a , R 2b and R 2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy;
  • R 6 is selected from C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1- 6alkylamino, diC1-6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino, wherein each of the C1- 6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkyl, C1-6alkyl
  • fungicide as used herein means a compound that controls, modifies, or prevents the growth of fungi.
  • fungicidally effective amount means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.
  • compounds of formula (I) as defined in the present invention as dressing agents for the treatment of plant propagation material, e.g., seed, such as fruits, tubers or grains, or plant cuttings (for example rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.
  • plant propagation material e.g., seed, such as fruits, tubers or grains, or plant cuttings (for example rice)
  • the propagation material can be treated with a composition comprising a compound of formula (I) as defined in the present invention before planting: seed, for example, can be dressed before being sown.
  • the compounds of formula (I) as defined in the present invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation.
  • the composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing.
  • the invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.
  • the compounds of formula (I) as defined in the present invention can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage, in hygiene management.
  • the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint.
  • Compounds of formula (I) as defined in the present invention and fungicidal compositions containing them may be used to control plant diseases caused by a broad spectrum of fungal plant pathogens.
  • fungi and fungal vectors of disease are for example: Absidia corymbifera, Alternaria spp, Aphanomyces spp, Ascochyta spp, Aspergillus spp. including A. flavus, A. fumigatus, A. nidulans, A. niger, A. terrus, Aureobasidium spp. including A.
  • Botryosphaeria spp. including B. dothidea, B. obtusa, Botrytis spp. contributing B. cinerea, Candida spp. including C. albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, C. tropicalis, Cephaloascus fragrans, Ceratocystis spp, Cercospora spp. including C.
  • capsulatum Laetisaria fuciformis, Leptographium lindbergi, Leveillula taurica, Lophodermium seditiosum, Microdochium nivale, Microsporum spp, Monilinia spp, Mucor spp, Mycosphaerella spp. including M. graminicola, M. pomi, Oncobasidium theobromaeon, Ophiostoma piceae, Paracoccidioides spp, Penicillium spp. including P. digitatum, P. italicum, Petriellidium spp, Peronosclerospora spp. Including P. maydis, P.
  • leucotricha Polymyxa graminis, Polymyxa betae, Pseudocercosporella herpotrichoides, Pseudomonas spp, Pseudoperonospora spp. including P. cubensis, P. humuli, Pseudopeziza tracheiphila, Puccinia Spp. including P. hordei, P. recondita, P. striiformis, P. triticina, Pyrenopeziza spp, Pyrenophora spp, Pyricularia spp. including P. oryzae, Pythium spp. including P.
  • compounds of formula (I) as defined in the present invention and fungicidal compositions containing them may be used to control plant diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and/or Deuteromycete, Blasocladiomycete, Chrytidiomycete, Glomeromycete and/or Mucoromycete classes. More particularly, the compounds of formula (I) as defined in the present invention may be used to conrol oomycetes.
  • pathogens may include: Oomycetes, including Phytophthora diseases such as those caused by Phytophthora capsici, Phytophthora infestans, Phytophthora sojae, Phytophthora fragariae, Phytophthora nicotianae, Phytophthora cinnamomi, Phytophthora citricola, Phytophthora citrophthora and Phytophthora erythroseptica; Pythium diseases such as those caused by Pythium aphanidermatum, Pythium arrhenomanes, Pythium graminicola, Pythium irregulare, Pythium sylvaticum and Pythium ultimum; diseases caused by Peronosporales such as Peronospora destructor, Peronospora parasitica, Plasmopara viticola, Plasmopara halstedii, Pseudoperonospora cubens
  • Ascomycetes including blotch, spot, blast or blight diseases and/or rots for example those caused by Pleosporales such as Stemphylium solani, Stagonospora tainanensis, Spilocaea oleaginea, Setosphaeria turcica, Pyrenochaeta lycoperisici, Pleospora herbarum, Phoma destructiva, Phaeosphaeria herpotrichoides, Phaeocryptocus gaeumannii, Ophiosphaerella graminicola, Ophiobolus graminis, Leptosphaeria maculans, Hendersonia creberrima, Helminthosporium triticirepentis, Setosphaeria turcica, Drechslera glycines, Didymella bryoniae, Cycloconium oleagineum, Corynespora cassiicola, Cochliobolus sativus, Bi
  • Gerlachia nivale Gibberella fujikuroi
  • Gibberella zeae Gibberella zeae
  • Gliocladium spp. Myrothecium verrucaria
  • Nectria ramulariae Trichoderma viride
  • Trichothecium roseum Trichothecium roseum
  • Verticillium theobromae Myrothecium verrucaria
  • Basidiomycetes including smuts for example those caused by Ustilaginales such as Ustilaginoidea virens, Ustilago nuda, Ustilago tritici, Ustilago zeae, rusts for example those caused by Pucciniales such as Cerotelium fici, Chrysomyxa arctostaphyli, Coleosporium ipomoeae, Hemileia vastatrix, Puccinia arachidis, Puccinia cacabata, Puccinia graminis, Puccinia recondita, Puccinia sorghi, Puccinia hordei, Puccinia striiformis f.sp.
  • Ustilaginales such as Ustilaginoidea virens, Ustilago nuda, Ustilago tritici, Ustilago zeae
  • rusts for example those caused by Pucciniales such as Cerotelium fici, Chr
  • Puccinia striiformis f.sp. Secalis Pucciniastrum coryli, or Uredinales such as Cronartium ribicola, Gymnosporangium juniperi-viginianae, Melampsora medusae, Phakopsora pachyrhizi, Phragmidium mucronatum, Physopella ampelosidis, Tranzschelia discolor and Uromyces viciae-fabae; and other rots and diseases such as those caused by Cryptococcus spp., Exobasidium vexans, Marasmiellus inoderma, Mycena spp., Sphacelotheca reiliana, Typhula ishikariensis, Urocystis agropyri, Itersonilia perplexans, Corticium invisum, Laetisaria fuciformis, Waitea circinata, Rhizoctonia solani, Tha
  • Blastocladiomycetes such as Physoderma maydis. Mucoromycetes, such as Choanephora cucurbitarum.; Mucor spp.; Rhizopus arrhizus. As well as diseases caused by other species and genera closely related to those listed above.
  • the compounds and compositions comprising compounds of formula (I) as defined in the present invention may also have activity against bacteria such as Erwinia amylovora, Erwinia caratovora, Xanthomonas campestris, Pseudomonas syringae, Strptomyces scabies and other related species as well as certain protozoa.
  • target crops and/or useful plants to be protected typically comprise perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St.
  • perennial and annual crops such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries
  • cereals for example barley, maize (corn), millet, oats
  • Augustine grass and Zoysia grass herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber; vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes.
  • herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme
  • legumes for example beans, lentils, peas and soya beans
  • the useful plants and / or target crops in accordance with the invention include conventional as well as genetically enhanced or engineered varieties such as, for example, insect resistant (e.g. Bt. and VIP varieties) as well as disease resistant, herbicide tolerant (e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®) and nematode tolerant varieties.
  • suitable genetically enhanced or engineered crop varieties include the Stoneville 5599BR cotton and Stoneville 4892BR cotton varieties.
  • useful plants and/or “target crops” is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5- enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering.
  • herbicides like bromoxynil or classes of herbicides
  • EPSPS 5- enol-pyrovyl-shikimate-3-phosphate-synthase
  • GS glutamine synthetase
  • PPO protoporphyrinogen-oxidase
  • An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola).
  • crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®.
  • the term "useful plants" and/or “target crops” is to be understood as including those which naturally are or have been rendered resistant to harmful insects.
  • toxins which can be expressed include ⁇ -endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins produced by scorpions, arachnids, wasps and fungi.
  • An example of a crop that has been modified to express the Bacillus thuringiensis toxin is the Bt maize KnockOut ⁇ (Syngenta Seeds).
  • VipCot ⁇ Surgera Seeds
  • Crops or seed material thereof can also be resistant to multiple types of pests (so-called stacked transgenic events when created by genetic modification).
  • a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant, for example Herculex I ⁇ (Dow AgroSciences, Pioneer Hi-Bred International).
  • useful plants and/or “target crops” is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0392225).
  • PRPs pathogenesis-related proteins
  • Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0392225, WO 95/33818, and EP-A-0353191.
  • the methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
  • Toxins that can be expressed by transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as ⁇ - endotoxins, e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp.
  • insecticidal proteins from Bacillus cereus or Bacillus popilliae such as ⁇ - endotoxins, e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative
  • Xenorhabdus spp. such as Photorhabdus luminescens, Xenorhabdus nematophilus
  • toxins produced by animals such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins
  • toxins produced by fungi such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins
  • agglutinins proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors
  • ribosome- inactivating proteins (RIP) such as ricin, maize-RIP, abrin, luffin, saporin or bryodin
  • steroid metabolism enzymes such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecd
  • ⁇ -endotoxins for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A
  • Vip vegetative insecticidal proteins
  • Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701).
  • Truncated toxins for example a truncated Cry1Ab, are known.
  • modified toxins one or more amino acids of the naturally occurring toxin are replaced.
  • preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G- recognition sequence is inserted into a Cry3A toxin (see WO03/018810).
  • More examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0374753, WO93/07278, WO95/34656, EP-A-0427529, EP-A-451878 and WO03/052073.
  • transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.
  • CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0367 474, EP-A-0401979 and WO 90/13651.
  • the toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects.
  • Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera).
  • Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard ⁇ (maize variety that expresses a Cry1Ab toxin); YieldGard Rootworm ⁇ (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus ⁇ (maize variety that expresses a Cry1Ab and a Cry3Bb1 toxin); Starlink ⁇ (maize variety that expresses a Cry9C toxin); Herculex I ⁇ (maize variety that expresses a Cry1Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B ⁇ (cotton variety that expresses a Cry1Ac toxin); Bollgard I
  • transgenic crops are: 1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31790 St.
  • This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence.
  • the preparation of such transgenic maize plants is described in WO 03/018810.
  • MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9.
  • MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5.
  • plants refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
  • plant propagation material is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes.
  • seeds in the strict sense
  • Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion.
  • plant propagation material is understood to denote seeds.
  • Pesticidal agents referred to herein using their common name are known, for example, from "The Pesticide Manual", 19th Ed., British Crop Protection Council 2021.
  • the compounds of formula (I) as defined in the present invention may be used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances.
  • compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.
  • Suitable carriers and/or adjuvants e.g. for agricultural use, can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers.
  • Suspension concentrates are aqueous formulations in which finely divided solid particles of the active compound are suspended.
  • Such formulations include anti-settling agents and dispersing agents and may further include a wetting agent to enhance activity as well an anti-foam and a crystal growth inhibitor.
  • these concentrates are diluted in water and normally applied as a spray to the area to be treated.
  • the amount of active ingredient may range from 0.5% to 95% of the concentrate.
  • Wettable powders are in the form of finely divided particles which disperse readily in water or other liquid carriers. The particles contain the active ingredient retained in a solid matrix.
  • Typical solid matrices include fuller’s earth, kaolin clays, silicas and other readily wet organic or inorganic solids.
  • Wettable powders normally contain from 5% to 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agent.
  • Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquid and may consist entirely of the active compound with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and normally applied as a spray to the area to be treated.
  • the amount of active ingredient may range from 0.5% to 95% of the concentrate.
  • Granular formulations include both extrudates and relatively coarse particles and are usually applied without dilution to the area in which treatment is required.
  • Typical carriers for granular formulations include sand, fuller’s earth, attapulgite clay, bentonite clays, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn cobs, ground peanut hulls, sugars, sodium chloride, sodium sulphate, sodium silicate, sodium borate, magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and other organic or inorganic materials which absorb or which can be coated with the active compound.
  • Granular formulations normally contain 5% to 25% of active ingredients which may include surface-active agents such as heavy aromatic naphthas, kerosene and other petroleum fractions, or vegetable oils; and/or stickers such as dextrins, glue or synthetic resins.
  • Dusts are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers.
  • Microcapsules are typically droplets or granules of the active ingredient enclosed in an inert porous shell which allows escape of the enclosed material to the surroundings at controlled rates. Encapsulated droplets are typically 1 to 50 microns in diameter.
  • the enclosed liquid typically constitutes 50 to 95% of the weight of the capsule and may include solvent in addition to the active compound.
  • Encapsulated granules are generally porous granules with porous membranes sealing the granule pore openings, retaining the active species in liquid form inside the granule pores.
  • Granules typically range from 1 millimetre to 1 centimetre and preferably 1 to 2 millimetres in diameter.
  • Granules are formed by extrusion, agglomeration or prilling, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and granular carbon.
  • Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.
  • Other useful formulations for agrochemical applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents.
  • Pressurised sprayers wherein the active ingredient is dispersed in finely-divided form as a result of vaporisation of a low boiling dispersant solvent carrier, may also be used.
  • Liquid carriers that can be employed include, for example, water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetonalcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl formamide, dimethyl sulfoxide,
  • Water is generally the carrier of choice for the dilution of concentrates.
  • suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay, fuller’s earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour and lignin.
  • a broad range of surface-active agents are advantageously employed in both said liquid and solid compositions, especially those designed to be diluted with carrier before application. These agents, when used, normally comprise from 0.1% to 15% by weight of the formulation.
  • Typical surface active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulphate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C.sub.18 ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol-C.sub.
  • soaps such as sodium stearate
  • alkylnaphthalenesulfonate salts such as sodium dibutylnaphthalenesulfonate
  • dialkyl esters of sulfosuccinate salts such as sodium di(2-ethylhexyl) sulfosuccinate
  • sorbitol esters such as sorbitol oleate
  • quaternary amines such as lauryl trimethylammonium chloride
  • polyethylene glycol esters of fatty acids such as polyethylene glycol stearate
  • block copolymers of ethylene oxide and propylene oxide and salts of mono and dialkyl phosphate esters.
  • compositions of the invention include crystallisation inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, anti- foaming agents, light-blocking agents, compatibilizing agents, antifoam agents, sequestering agents, neutralising agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants and sticking agents.
  • biocidally active ingredients or compositions may be combined with the compositions of the invention and used in the methods of the invention and applied simultaneously or sequentially with the compositions of the invention.
  • these further active ingredients may be formulated together with the compositions of the invention or mixed in, for example, the spray tank.
  • These further biocidally active ingredients may be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides, plant growth regulators, and/or biologicals.
  • TX means “one compound selected from the compounds defined in the Tables 1.1 to 1.162 and Table A): an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX; abamectin + TX, acequinocyl + TX, acetamiprid + TX, acetoprole + TX, acrinathrin + TX, acynonapyr + TX, afidopyropen + TX, afoxolaner + TX, alanycarb + TX, allethrin + TX, alpha-cypermethrin + TX, alphamethrin + TX, amidoflumet + TX, aminocarb + TX, azocyclotin + TX, bensultap + TX, benzoximate + TX, benzpyrim
  • TX Neem tree based products + TX, Paecilomyces fumosoroseus + TX, Paecilomyces lilacinus + TX, Pasteuria nishizawae + TX, Pasteuria penetrans + TX, Pasteuria ramosa + TX, Pasteuria thornei + TX, Pasteuria usgae + TX, P-cymene + TX, Plutella xylostella Granulosis virus + TX, Plutella xylostella Nucleopolyhedrovirus + TX, Polyhedrosis virus + TX, pyrethrum + TX, QRD 420 (a terpenoid blend) + TX, QRD 452 (a terpenoid blend) + TX, QRD 460 (a terpenoid blend) + TX, Quillaja saponaria + TX, Rhodococc
  • TX Paecilomyces fumosoroseus + TX, Phytoseiulus persimilis + TX, Steinernema bibionis + TX, Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. + TX, Trichogramma spp.
  • the compounds in this paragraph may be prepared from the methods described in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689; 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3- pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol + TX (this compound may be prepared from the methods described in WO 2017/029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1- yl)propan-2-ol + TX (this compound may be prepared from the methods described in WO 2017/029179); 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound may be prepared from the methods described in WO 2016/156
  • TX Aureobasidium pullulans + TX, Azospirillum (MicroAZ®, TAZO B®) + TX, Azotobacter + TX, Azotobacter chroocuccum (Azotomeal®) + TX, Azotobacter cysts (Bionatural Blooming Blossoms®) + TX, Bacillus amyloliquefaciens + TX, Bacillus cereus + TX, Bacillus chitinosporus strain CM-1 + TX, Bacillus chitinosporus strain AQ746 + TX, Bacillus licheniformis strain HB-2 (e.g, BiostartTM, formerly Rhizoboost®) + TX, Bacillus licheniformis strain 3086 (EcoGuard®, Green Releaf®) + TX, Bacillus circulans + TX, Bacillus firmus (BioSafe®, BioNem-WP®, VOTiVO®) + TX,
  • Bacillus subtilis strain AQ178 + TX Bacillus subtilis strain QST 713 (CEASE®, Serenade®, Rhapsody®) + TX, Bacillus subtilis strain QST 714 (JAZZ®) + TX, Bacillus subtilis strain AQ153 + TX, Bacillus subtilis strain AQ743 + TX, Bacillus subtilis strain QST3002 + TX, Bacillus subtilis strain QST3004 + TX, Bacillus subtilis var.
  • amyloliquefaciens strain FZB24 (Taegro®, Rhizopro®) + TX, Bacillus thuringiensis Cry 2Ae + TX, Bacillus thuringiensis Cry1Ab + TX, Bacillus thuringiensis aizawai GC 91 (Agree®) + TX, Bacillus thuringiensis israelensis (BMP123®, Aquabac®, VectoBac®) + TX, Bacillus thuringiensis kurstaki (Javelin®, Deliver®, CryMax®, Bonide®, Scutella WP®, Turilav WP®, Astuto®, Dipel WP®, Biobit®, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®) + TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF / 3P®) + TX,
  • TX Botrytis cineria + TX, Bradyrhizobium japonicum (TerraMax®) + TX, Brevibacillus brevis + TX, Bacillus thuringiensis tenebrionis (Novodor®) + TX, BtBooster + TX, Burkholderia cepacia (Deny®, Intercept®, Blue Circle®) + TX, Burkholderia gladii + TX, Burkholderia gladioli + TX, Burkholderia spp.
  • TX Canadian thistle fungus (CBH Canadian Bioherbicide®) + TX, Candida butyri + TX, Candida famata + TX, Candida fructus + TX, Candida glabrata + TX, Candida guilliermondii + TX, Candida melibiosica + TX, Candida oleophila strain O + TX, Candida parapsilosis + TX, Candida pelliculosa + TX, Candida pulcherrima + TX, Candida reuêtii + TX, Candida saitoana (Bio-Coat®, Biocure®) + TX, Candida sake + TX, Candida spp.
  • TX Cladosporium tenuissimum + TX, Clonostachys rosea (EndoFine®) + TX, Colletotrichum acutatum + TX, Coniothyrium minitans (Cotans WG®) + TX, Coniothyrium spp.
  • TX Filobasidium floriforme + TX, Fusarium acuminatum + TX, Fusarium chlamydosporum + TX, Fusarium oxysporum (Fusaclean®, Biofox C®) + TX, Fusarium proliferatum + TX, Fusarium spp. + TX, Galactomyces geotrichum + TX, Gliocladium catenulatum (Primastop®, Prestop®) + TX, Gliocladium roseum + TX, Gliocladium spp.
  • Pasteuria spp. Econem® + TX, Pasteuria nishizawae + TX, Penicillium aurantiogriseum + TX, Penicillium billai (Jumpstart®, TagTeam®) + TX, Penicillium brevicompactum + TX, Penicillium frequentans + TX, Penicillium griseofulvum + TX, Penicillium purpurogenum + TX, Penicillium spp.
  • TX Penicillium viridicatum + TX, Phlebiopsis gigantean (Rotstop®) + TX, phosphate solubilizing bacteria (Phosphomeal®) + TX, Phytophthora cryptogea + TX, Phytophthora palmivora (Devine®) + TX, Pichia anomala + TX, Pichia guilermondii + TX, Pichia membranaefaciens + TX, Pichia onychis + TX, Pichia stipites + TX, Pseudomonas aeruginosa + TX, Pseudomonas aureofasciens (Spot-Less Biofungicide®) + TX, Pseudomonas cepacia + TX, Pseudomonas chlororaphis (AtEze®) + TX, Pseudomonas corrugate + TX, Ps
  • Rhodosporidium diobovatum + TX Rhodosporidium toruloides + TX, Rhodotorula spp.
  • Trichoderma asperellum T34 Biocontrol®
  • Trichoderma gamsii TX
  • Trichoderma atroviride Plantmate®
  • Trichoderma harzianum rifai Mycostar®
  • Trichoderma harzianum T-22 Trianum-P®, PlantShield HC®, RootShield®, Trianum-G®) + TX
  • Trichoderma harzianum T-39 Trichodex®) + TX, Trichoderma inhamatum + TX, Trichoderma koningii + TX, Trichoderma spp.
  • LC 52 (Sentinel®) + TX, Trichoderma lignorum + TX, Trichoderma longibrachiatum + TX, Trichoderma polysporum (Binab T®) + TX, Trichoderma taxi + TX, Trichoderma virens + TX, Trichoderma virens (formerly Gliocladium virens GL- 21) (SoilGuard®) + TX, Trichoderma viride + TX, Trichoderma viride strain ICC 080 (Remedier®) + TX, Trichosporon pullulans + TX, Trichosporon spp. + TX, Trichothecium spp.
  • TX Trichothecium roseum + TX, Typhula phacorrhiza strain 94670 + TX, Typhula phacorrhiza strain 94671 + TX, Ulocladium atrum + TX, Ulocladium oudemansii (Botry-Zen®) + TX, Ustilago maydis + TX, various bacteria and supplementary micronutrients (Natural II®) + TX, various fungi (Millennium Microbes®) + TX, Verticillium chlamydosporium + TX, Verticillium lecanii (Mycotal®, Vertalec®) + TX, Vip3Aa20 (VIPtera®) + TX, Virgibaclillus marismortui + TX, Xanthomonas campestris pv.
  • Plant extracts including: pine oil (Retenol®) + TX, azadirachtin (Plasma Neem Oil®, AzaGuard®, MeemAzal®, Molt-X®) + TX, Botanical IGR (Neemazad®, Neemix®) + TX, canola oil (Lilly Miller Vegol®) + TX, Chenopodium ambrosioides near ambrosioides (Requiem®) + TX, Chrysanthemum extract (Crisant®) + TX, extract of neem oil (Trilogy®) + TX, essentials oils of Labiatae (Botania®) + TX, extracts of clove rosemary peppermint and thyme oil (Garden insect killer®) + TX, Glycinebetaine (Greenstim®
  • TX Coccidoxenoides perminutus (Planopar®) + TX, Coccophagus cowperi + TX, Coccophagus lycimnia + TX, Cotesia flavipes + TX, Cotesia plutellae + TX, Cryptolaemus montrouzieri (Cryptobug®, Cryptoline®) + TX, Cybocephalus nipponicus + TX, Dacnusa sibirica + TX, Dacnusa sibirica (Minusa®) + TX, Diglyphus isaea (Diminex®) + TX, Delphastus catalinae (Delphastus®) + TX, Delphastus pusillus + TX, Diachasmimorpha krausii + TX, Diachasmimorpha longicaudata + TX, Diaparsis jucunda + TX, Diaphorencyrtus aligarhensis + TX
  • TX Steinernematid spp. (Guardian Nematodes®) + TX, Stethorus punctillum (Stethorus®) + TX, Tamarixia radiate + TX, Tetrastichus setifer + TX, Thripobius semiluteus + TX, Torymus sinensis + TX, Trichogramma brassicae (Tricholine b®) + TX, Trichogramma brassicae (Tricho-Strip®) + TX, Trichogramma evanescens + TX, Trichogramma minutum + TX, Trichogramma ostriniae + TX, Trichogramma platneri + TX, Trichogramma pretiosum + TX, Xanthopimpla stemmator + TX; other biologicals including: abscisic acid + TX, bioSea® + TX, Chondrostereum purpureum (Chontrol Paste®) + TX, Colletotrichum gloeospor
  • NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC + TX
  • Bacillus pumilus in particular strain BU F-33, having NRRL Accession No.50185 (CARTISSA® from BASF, EPA Reg. No.71840-19) + TX
  • Bacillus subtilis in particular strain QST713/AQ713 (SERENADE OPTI or SERENADE ASO from Bayer CropScience LP, US, having NRRL Accession No. B21661, U.S.
  • Patent No.6,060,051 + TX
  • Bacillus subtilis strain BU1814 (VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX
  • Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No.70127-5)) + TX
  • Bacillus subtilis CX-9060 from Certis USA LLC + TX
  • Bacillus sp. in particular strain D747 (available as DOUBLE NICKEL® from Kumiai Chemical Industry Co., Ltd.), having Accession No.
  • Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297 + TX; Paenibacillus polymyxa, in particular strain AC- 1 (e.g. TOPSEED® from Green Biotech Company Ltd.) + TX; Pantoea agglomerans, in particular strain E325 (Accession No. NRRL B-21856) (available as BLOOMTIME BIOLOGICALTM FD BIOPESTICIDE from Northwest Agri Products) + TX; Pseudomonas proradix (e.g.
  • PRORADIX® from Sourcon Padena) + TX; and (1.2) fungi, examples of which are Aureobasidium pullulans, in particular blastospores of strain DSM14940, blastospores of strain DSM 14941 or mixtures of blastospores of strains DSM14940 and DSM14941 (e.g., BOTECTOR® and BLOSSOM PROTECT® from bio-ferm, CH) + TX; Pseudozyma aphidis (as disclosed in WO2011/151819 by Yissum Research Development Company of the Hebrew University of Jerusalem) + TX; Saccharomyces cerevisiae, in particular strains CNCM No.
  • CNCM No.1-3937, CNCM No.1-3938 or CNCM No.1-3939 (as disclosed in WO 2010/086790 from Lesaffre et Compagnie, FR) + TX;
  • biological fungicides selected from the group of: (2.1) bacteria, examples of which are Agrobacterium radiobacter strain K84 (e.g. GALLTROL-A® from AgBioChem, CA) + TX; Agrobacterium radiobacter strain K1026 (e.g. NOGALLTM from BASF SE) + TX; Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No.
  • DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No. 70127-5)) + TX; Bacillus amyloliquefaciens, in particular strain D747 (available as Double NickelTM from Kumiai Chemical Industry Co., Ltd., having accession number FERM BP-8234, US Patent No.7,094,592) + TX; Bacillus amyloliquefaciens strain F727 (also known as strain MBI110) (NRRL Accession No. B-50768, WO 2014/028521) (STARGUS® from Marrone Bio Innovations) + TX; Bacillus amyloliquefaciens strain FZB42, Accession No.
  • DSM 23117 available as RHIZOVITAL® from ABiTEP, DE
  • TX Bacillus amyloliquefaciens isolate B246 (e.g. AVOGREENTM from University of Pretoria) + TX
  • Bacillus licheniformis in particular strain SB3086, having Accession No.
  • ATCC 55406, WO 2003/000051 (available as ECOGUARD® Biofungicide and GREEN RELEAFTM from Novozymes) + TX; Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (QUARTZO® (WG) and PRESENCE® (WP) from FMC Corporation) + TX; Bacillus methylotrophicus strain BAC-9912 (from Chinese Academy of Sciences’ Institute of Applied Ecology) + TX; Bacillus mojavensis strain R3B (Accession No. NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC + TX; Bacillus mycoides, isolate, having Accession No.
  • Bacillus pumilus, in particular strain QST2808 (available as SONATA® from Bayer CropScience LP, US, having Accession No. NRRL B-30087 and described in U.S. Patent No.6,245,551) + TX
  • Bacillus pumilus, in particular strain GB34 (available as Yield Shield® from Bayer AG, DE) + TX
  • Bacillus pumilus, in particular strain BU F-33 having NRRL Accession No. 50185 (available as part of the CARTISSA product from BASF, EPA Reg.
  • Bacillus subtilis in particular strain QST713/AQ713 (available as SERENADE OPTI or SERENADE ASO from Bayer CropScience LP, US, having NRRL Accession No. B21661 and described in U.S. Patent No. 6,060,051) + TX; Bacillus subtilis Y1336 (available as BIOBAC® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos.4764, 5454, 5096 and 5277) + TX; Bacillus subtilis strain MBI 600 (available as SUBTILEX from BASF SE), having Accession Number NRRL B-50595, U.S.
  • Patent No.5,061,495 + TX Bacillus subtilis strain GB03 (available as Kodiak® from Bayer AG, DE) + TX; Bacillus subtilis strain BU1814, (available as VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX; Bacillus subtilis CX-9060 from Certis USA LLC + TX; Bacillus subtilis KTSB strain (FOLIACTIVE® from Donaghys) + TX; Bacillus subtilis IAB/BS03 (AVIVTM from STK Bio-Ag Technologies, PORTENTO® from Idai Nature) + TX; Bacillus subtilis strain Y1336 (available as BIOBAC® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos.4764, 5454, 5096 and 5277) + TX; Paenibacillus epiphyticus (WO 2016/020371) from BASF SE + TX; Paen
  • CEDOMON®, CERALL®, and CEDRESS® by Bioagri and Koppert TX
  • Pseudomonas fluorescens strain A506 e.g. BLIGHTBAN® A506 by NuFarm
  • Pseudomonas proradix e.g. PRORADIX® from Sourcon Padena
  • Streptomyces griseoviridis strain K61 also known as Streptomyces galbus strain K61
  • DSM 7206 Streptomyces griseoviridis strain K61 (also known as Streptomyces galbus strain K61) (Accession No. DSM 7206) (MYCOSTOP® from Verdera, PREFENCE® from BioWorks, cf.
  • Streptomyces lydicus strain WYEC108 also known as Streptomyces lydicus strain WYCD108US
  • ACTINO-IRON® and ACTINOVATE® from Novozymes + TX
  • fungi examples of which are Ampelomyces quisqualis, in particular strain AQ 10 (e.g. AQ 10® by IntrachemBio Italia) + TX
  • Ampelomyces quisqualis strain AQ10 having Accession No.
  • CNCM 1-807 e.g., AQ 10® by IntrachemBio Italia
  • TX Aspergillus flavus strain NRRL 21882 (products known as AFLA-GUARD® from Syngenta/ChemChina) + TX
  • Aureobasidium pullulans in particular blastospores of strain DSM14940 + TX
  • Aureobasidium pullulans in particular blastospores of strain DSM 14941 + TX
  • Aureobasidium pullulans in particular mixtures of blastospores of strains DSM14940 and DSM 14941 (e.g. Botector® by bio-ferm, CH) + TX
  • Chaetomium cupreum accesion No.
  • CABI 353812 e.g. BIOKUPRUMTM by AgriLife
  • TX Chaetomium globosum (available as RIVADIOM® by Rivale) + TX
  • Coniothyrium minitans, in particular strain CON/M/91-8 accesion No. DSM9660, e.g.
  • Prestop ® by Lallemand + TX; Gliocladium roseum (also known as Clonostachys rosea f rosea), in particular strain 321U from Adjuvants Plus, strain ACM941 as disclosed in Xue A.G (Efficacy of Clonostachys rosea strain ACM941 and fungicide seed treatments for controlling the root tot complex of field pea, Can. J. Plant Sci.2003, 83(3): 519-524), or strain IK726 (Jensen DF, et al. Development of a biocontrol agent for plant disease control with special emphasis on the near commercial fungal antagonist Clonostachys rosea strain ’IK726’, Australasian Plant Pathol.
  • Trichoderma asperellum in particular, strain kd (e.g. T-Gro from Andermatt Biocontrol) + TX; Trichoderma asperellum, in particular strain SKT-1, having Accession No. FERM P-16510 (e.g. ECO- HOPE® from Kumiai Chemical Industry), strain T34 (e.g. T34 Biocontrol by Biocontrol Technologies S.L., ES) or strain ICC 012 from Isagro + TX; Trichoderma atroviride, in particular strain SC1 (Accession No. CBS 122089, WO 2009/116106 and U.S.
  • Patent No.8,431,120 from Bi-PA
  • strain 77B T77 from Andermatt Biocontrol
  • strain LU132 e.g. Sentinel from Agrimm Technologies Limited
  • Trichoderma atroviride strain CNCM 1-1237 (e.g. Esquive® WP from Agrauxine, FR) + TX
  • Trichoderma atroviride strain no. V08/002387 + TX
  • Trichoderma atroviride strain NMI no. V08/002388 + TX
  • Trichoderma atroviride strain NMI no. V08/002389 + TX
  • Trichoderma atroviride strain NMI no.
  • Trichoderma atroviride Trichoderma atroviride, strain LC52 (e.g. Tenet by Agrimm Technologies Limited) + TX; Trichoderma atroviride, strain ATCC 20476 (IMI 206040) + TX; Trichoderma atroviride, strain T11 (IMI352941/ CECT20498) + TX; Trichoderma atroviride, strain SKT-1 (FERM P-16510), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma atroviride, strain SKT-2 (FERM P-16511), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma atroviride, strain SKT-3 (FERM P-17021), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma fertile (e.g.
  • TrichoPlus from BASF + TX
  • Trichoderma gamsii (formerly T. viride), strain ICC080 (IMI CC 392151 CABI, e.g. BioDerma by AGROBIOSOL DE MEXICO, S.A. DE C.V.) + TX
  • Trichoderma gamsii (formerly T. viride), strain ICC 080 (IMI CC 392151 CABI) (available as BIODERMA® by AGROBIOSOL DE MEXICO, S.A. DE C.V.) + TX
  • Trichoderma harmatum having Accession No. ATCC 28012 + TX
  • Trichoderma harzianum strain T-22 e.g.
  • Trianum-P from Andermatt Biocontrol or Koppert or strain Cepa SimbT5 (from Simbiose Agro) + TX; Trichoderma harzianum + TX; Trichoderma harzianum rifai T39 (e.g. Trichodex® from Makhteshim, US) + TX; Trichoderma harzianum, strain ITEM 908 (e.g. Trianum-P from Koppert) + TX; Trichoderma harzianum, strain TH35 (e.g.
  • Trichoderma harzianum strain DB 103 (available as T-GRO® 7456 by Dagutat Biolab) + TX
  • Trichoderma polysporum strain IMI 206039 (e.g. Binab TF WP by BINAB Bio-Innovation AB, Sweden) + TX
  • Trichoderma stromaticum having Accession No. Ts3550 (e.g. Tricovab by CEPLAC, Brazil) + TX
  • Trichoderma virens also known as Gliocladium virens
  • strain GL-21 e.g.
  • Trichoderma virens strain G-41 formerly known as Gliocladium virens (Accession No. ATCC 20906) (e.g., ROOTSHIELD® PLUS WP and TURFSHIELD® PLUS WP from BioWorks, US) + TX; Trichoderma viride, strain TV1(e.g. Trianum-P by Koppert) + TX; Trichoderma viride, in particular strain B35 (Pietr et al., 1993, Zesz. Nauk.
  • NM 99/06216 e.g., BOTRY-ZEN® by Botry-Zen Ltd, New Zealand and BOTRYSTOP® from BioWorks, Inc.
  • Verticillium albo-atrum previously V. dahliae
  • strain WCS850 having Accession No.
  • WCS850 deposited at the Central Bureau for Fungi Cultures (e.g., DUTCH TRIG® by Tree Care Innovations) + TX; Verticillium chlamydosporium + TX; (3) biological control agents having an effect for improving plant growth and/or plant health selected from the group of: (3.1) bacteria, examples of which are Azospirillum brasilense (e.g., VIGOR® from KALO, Inc.) + TX; Azospirillum lipoferum (e.g., VERTEX-IFTM from TerraMax, Inc.) + TX; Azorhizobium caulinodans, in particular strain ZB-SK-5 + TX; Azotobacter chroococcum, in particular strain H23 + TX; Azotobacter vinelandii, in particular strain ATCC 12837 + TX; a mixture of Azotobacter vinelandii and Clostridium pasteurianum (available as INVIGORATE® from Agrinos)
  • Bacillus pumilus in particular strain QST2808 (Accession No. NRRL No. B-30087) + TX; Bacillus pumilus, in particular strain GB34 (e.g.
  • Bacillus subtilis strain BU1814 (available as TEQUALIS® from BASF SE), Bacillus subtilis rm303 (RHIZOMAX® from Biofilm Crop Protection) + TX; Bacillus thuringiensis BT013A (NRRL No. B-50924) also known as Bacillus thuringiensis 4Q7 + TX; a mixture of Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (available as QUARTZO® (WG), PRESENCE® (WP) from FMC Corporation) + TX; Bacillus subtilis, in particular strain MBI 600 (e.g.
  • SUBTILEX® from BASF SE + TX
  • Bacillus tequilensis in particular strain NII-0943 + TX
  • Bradyrhizobium japonicum e.g. OPTIMIZE® from Novozymes
  • Delftia acidovorans in particular strain RAY209 (e.g. BIOBOOST® from Brett Young Seeds) + TX
  • Mesorhizobium cicer e.g., NODULATOR from BASF SE
  • Lactobacillus sp. e.g.
  • Trichoderma atroviride strain CNCM 1-1237 e.g. Esquive® WP from Agrauxine, FR
  • Trichoderma viride e.g. strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161: 125-137) + TX; Trichoderma atroviride strain LC52 (also known as Trichoderma atroviride strain LU132, e.g.
  • Bacillus sphaericus in particular Serotype H5a5b strain 2362 (strain ABTS-1743) (e.g. VECTOLEX® from Valent BioSciences, US) + TX; Bacillus thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372, e.g. XENTARI® from Valent BioSciences) + TX; Bacillus thuringiensis subsp. aizawai, in particular serotype H-7 (e.g.
  • israeltaki strain EG 7841 (CRYMAX® from Certis, US) + TX; Bacillus thuringiensis subsp. tenebrionis strain NB 176 (SD-5428, e.g. NOVODOR® FC from BioFa DE) + TX; Brevibacillus laterosporus (LATERAL® from Ecolibrium Biologicals) + TX; Burkholderia spp., in particular Burkholderia rinojensis strain A396 (also known as Burkholderia rinojensis strain MBI 305) (Accession No. NRRL B-50319); WO 2011/106491 and WO 2013/032693; e.g.
  • compositions of the invention may also be applied with one or more systemically acquired resistance inducers (“SAR” inducer).
  • SAR inducers are known and described in, for example, United States Patent No. US 6,919,298 and include, for example, salicylates and the commercial SAR inducer acibenzolar-S-methyl.
  • the compounds of formula (I) as defined in the present invention are normally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations, which influence the growth of plants.
  • They can also be selective herbicides or non- selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.
  • the compounds of formula (I) as defined in the present invention may be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula (I) as defined in any one of embodiments 1 to 43 or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.
  • the invention therefore provides a composition, preferably a fungicidal composition, comprising at least one compound of formula (I) as defined in the present invention, an agriculturally acceptable carrier and optionally an adjuvant.
  • An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use. Agricultural carriers are well known in the art.
  • composition may comprise at least one or more pesticidally active compounds, for example an additional fungicidal active ingredient in addition to the compound of formula (I) as defined in the present invention.
  • a further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g.
  • Controlling or preventing means reducing infestation by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.
  • a preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, which comprises the application of a compound of formula (I) as defined in the present invention, or an agrochemical composition which contains at least one of said compounds, is foliar application.
  • the frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen or insect.
  • the compounds of formula (I) as defined in the present invention can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field.
  • compositions that is the methods of controlling pathogens of the abovementioned type, such as spraying, atomizing, dusting, brushing on, dressing, scattering or pouring - which are to be selected to suit the intended aims of the prevailing circumstances - and the use of the compositions for controlling pathogens of the abovementioned type are other subjects of the invention.
  • Typical rates of concentration are between 0.1 and 1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient.
  • the rate of application per hectare is preferably 1g to 2000 g of active ingredient per hectare, more preferably 10 to 1000 g/ha, most preferably 10 to 600 g/ha.
  • a composition comprising a compound of formula (I) as defined in the present invention according to the present invention is applied either preventative, meaning prior to disease development or curative, meaning after disease development.
  • compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK
  • a seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds.
  • suitable seed dressing formulation form e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds.
  • seed dressing formulations are known in the art.
  • Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g.
  • the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula (I) as defined in the present invention together with component (B) and (C), and optionally other active agents, particularly microbiocides or conservatives or the like.
  • Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent.
  • Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent.
  • Compounds of Formula (I) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).
  • advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability).
  • temperatures are given in degrees Celsius (°C) and “MP” means melting point.
  • LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the methods are described below.
  • Wettable powders a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % sodium lignosulfonate 5 % 5 % - sodium lauryl sulfate 3 % - 5 % sodium diisobutylnaphthalenesulfonate - 6 % 10 % phenol polyethylene glycol ether - 2 % - (7-8 mol of ethylene oxide) highly dispersed silicic acid 5 % 10 % 10 % Kaolin 62 % 27 % -
  • the active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
  • Powders for dry seed treatment a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % light mineral oil 5 % 5 % 5 % highly dispersed silicic acid 5 % 5 % - Kaolin 65 % 40 % - Talcum - 20%
  • active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment.
  • Emulsifiable concentrate active ingredient [compound of formula (I)] 10 % octylphenol polyethylene glycol ether 3 % (4-5 mol of ethylene oxide) calcium dodecylbenzenesulfonate 3 % castor oil polyglycol ether (35 mol of ethylene oxide) 4 % Cyclohexanone 30 % xylene mixture 50 % Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
  • Coated granules Active ingredient [compound of formula (I)] 8 % polyethylene glycol (mol. wt.200) 3 % Kaolin 89 % The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
  • Suspension concentrate active ingredient [compound of formula (I)] 40 % propylene glycol 10 % nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 % Sodium lignosulfonate 10 % carboxymethylcellulose 1 % silicone oil (in the form of a 75 % emulsion in water) 1 % Water 32 %
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion.
  • Flowable concentrate for seed treatment active ingredient [compound of formula (I)] 40 % propylene glycol 5 % copolymer butanol PO/EO 2 % tristyrenephenole with 10-20 moles EO 2 % 1,2-benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5 % monoazo-pigment calcium salt 5 % Silicone oil (in the form of a 75 % emulsion in water) 0.2 % Water 45.3 % The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
  • a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added.
  • the mixture is agitated until the polymerization reaction is completed.
  • the obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent.
  • the capsule suspension formulation contains 28% of the active ingredients.
  • the medium capsule diameter is 8-15 microns.
  • the resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
  • Method B Spectra were recorded on a Mass Spectrometer from Waters (Acquity QDa Mass Spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch), Capillary: 0.8 kV, Cone range: 25 V, Extractor: V (No extractor voltage for QDa detector) Source Temperature: 120°C, Desolvation Temperature: 600°C, Cone Gas Flow: 50 L/h, Desolvation Gas Flow: 1000 L/h, Mass range: 110 to 850 Da) and an Acquity UPLC from Waters: Quaternary solvent manager, heated column compartment , diode-array detector.
  • Method C Spectra were recorded on a Mass Spectrometer from Waters Corporation (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 0.8-3.00 kV, Cone: 5-30 V, Source Temperature: 120-150°C, Desolvation Temperature: 350-600°C, Cone Gas Flow: 50-150 l/h, Desolvation Gas Flow: 650-1000 l/h, Mass range: 110 to 950 Da and an Acquity UPLC from Waters Corporation: Binary pump, heated column compartment, diode- array detector and ELSD.
  • Method E Spectra were recorded on a Mass Spectrometer from Agilent (Single quad mass spectrometer) equipped with a Multimode- Electron Spray and APCI (Polarity: positive and negative ions), Capillary: 4.00 kV, Corona Current 4.0 ⁇ A, Charging Voltage: 2.00 kV, Nitrogen Gas Flow: 12.0 L/min, Nebulizer Pressure: 40 psig, Mass range: 100 to 1000 m/z), dry gas temperature 250 °C, Vaporizer temperature 200 °C and an UPLC from Waters: quaternary pump, heated column compartment, Variable wave length detector.
  • Agilent Single quad mass spectrometer
  • APCI Multimode- Electron Spray and APCI
  • Method F Spectra were recorded on a on a Mass Spectrometer from Agilent (Single quad mass spectrometer) equipped with Electron Spray (Polarity: positive and negative ions), Capillary: 4.00 kV, Charging Voltage: 2.00 kV, Nitrogen Gas Flow: 12.0 L/min, Nebulizer Pressure: 40 psig, Mass range: 100 to 1000 m/z, dry gas temperature 250 °C, Vaporizer temperature 200 °C and an UPLC from Waters: quaternary pump, heated column compartment, Variable wave length detector.
  • potassium carbonate (4.93 g, 35.7 mmol, 1.00 eq.) was added to a solution of prop-2-en-1-amine (6.11 g, 107 mmol, 3.00 eq.) in dichloromethane (50.0 mL).
  • the mixture of amine was added to the solution of the acid chloride in dichloromethane (50.0 mL).
  • the resulting reaction mixture was stirred at room temperature for 24 hours, then it was diluted with saturated aqueous NaHCO3 solution and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 3 Preparation of N'-allyl-N-(3-bromoimidazo[1,2-a]pyridin-6-yl)-4-fluoro-benzamidine
  • Example 2 preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 65) N To a mixture of 6-bromo-3-chloro-imidazo[1,2-a]pyridine (100 mg, 0.432 mmol) and 1H-pyrazol-3- ylboronic acid (48.3 mg, 0.432 mmol, 1.00 eq.) in dioxane/water (8:3, 5.00 mL) was added Pd(dppf)Cl2 (31.6 mg, 0.0432 mmol, 0.100 eq.) and potassium carbonate (179 mg, 1.30 mmol, 3.00 eq.).
  • Pd(dppf)Cl2 (7 mg, 0.01 mmol, 0.10 eq.) and potassium carbonate (40 mg, 0.29 mmol, 3.0 eq.) were added and the mixture was heated at 80 °C for 2 hours under nitrogen atmosphere. The reaction mixture was cooled down, diluted with water, and extracted with dichloromethane.
  • Example 3 preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 19) (Compound 19) Step 1: Preparation of (4-bromo-2,5-dimethyl-pyrazol-3-yl) trifluoromethanesulfonate To a solution of 2,5-dimethyl-4H-pyrazol-3-one (3.00 g, 26.8 mmol) in dichloromethane (50.0 mL) was added 1-bromopyrrolidine-2,5-dione (5.00 g, 28.1 mmol, 1.05 eq.) at 0 °C.
  • reaction mixture was stirred at 0 °C for 30 minutes, after which 2,6-dimethylpyridine (6.23 mL, 53.5 mmol, 2.00 eq.) and trifluoromethanesulfonic anhydride (5.40 mL, 32.1 mmol, 1.20 eq.) were added.
  • the reaction mixture was stirred at 0 °C for 1 hour, and then it was diluted with a NaHCO3 solution, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • reaction mixture was stirred at 80 °C for 4 hours, after which it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 3-chloro-6-[5-(4-fluoro-3-methoxy-phenyl)-1,3- dimethyl-pyrazol-4-yl]imidazo[1,2-a]pyridine as a brown oil.
  • Example 4 preparation of methyl N-[5-[6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 38) (Compound 38) Step 1: Preparation of 2-chloro-5-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]pyridine A solution of 4-fluorobenzamide (2.80 g, 20.1 mmol) in 1,1-dimethoxy-N,N-dimethyl-methanamine (14.0 mL) was heated at 100 °C for 2 h.
  • reaction mixture was stirred at 80 °C for 4 hours, after which it was diluted with water and extracted with dichloromethane. The combined organic phases were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford N-(2,2-dimethoxyethyl)-5-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]pyridin-2-amine as a yellow oil.
  • Pd(dppf)Cl2 (9.0 mg, 0.012 mmol, 0.10 eq.) and potassium carbonate (43 mg, 0.31 mmol, 2.50 eq.) were added under nitrogen and the mixture was heated at 65 °C and stirred for 3 hours. The mixture was cooled down, diluted with water, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • reaction mixture was stirred for an additional 2 hours at room temperature, and then it was quenched with water resulting in the formation of a white solid in the aqueous layer.
  • the mixture was filtered, the filter cake was washed with water and the residue was dried under reduced pressure to afford 6-(4-bromo-2-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine as a brown solid.
  • reaction mixture was heated at 80 °C and stirred for 2 hours under a nitrogen atmosphere.
  • the reaction mixture was then concentrated under reduced pressure and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 3-chloro-6-[4-(4-fluorophenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2- a]pyridine as a yellow oil.
  • reaction mixture was heated at 80 °C and stirred for 2 hours under a nitrogen atmosphere.
  • the reaction mixture was then cooled, diluted with water and extracted with dichloromethane.
  • the combined organic layers were concentrated under reduced pressure and the crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford the desired target which was further purified by trituration with acetonitrile to afford 5-(4-fluoro-3- methoxy-phenyl)-1-methyl-pyrazole as a colorless oil.
  • reaction mixture was heated at 80 °C and stirred for 2 hours under nitrogen atmosphere.
  • the combined organic layers were concentrated under reduced pressure and the resulting residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford the desired target, which was further purified by trituration with acetonitrile to ultimately afford 3-chloro-6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-4- yl]imidazo[1,2-a]pyridine as a white solid.
  • Example 7 preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-oxo-1,2,4-oxadiazol- 3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 32)
  • N Compound 32
  • Step 1 Preparation of N-hydroxyimidazo[1,2-a]pyridine-6-carboxamidine
  • reaction mixture was then cooled and concentrated under reduced pressure to remove the pyridine.
  • the cooled reaction mixture was then washed with tert-butyl methyl ether to obtain a crude residue that was further purified by washing with water. Drying the resulting solid in vacuo afforded 3-imidazo[1,2-a]pyridin-6-yl-4H-1,2,4-oxadiazol-5-one as a brown solid.
  • reaction mixture was heated at 45 °C and stirred for 1 hour under an atmosphere of nitrogen.
  • the reaction mixture was then concentrated under reduced pressure, and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to give the desired compound, which was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[4- (4-fluoro-3-methoxy- phenyl)-5-oxo-1,2,4-oxadiazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white powder.
  • Example 8 preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 47) (Compound 47) Step 1: Preparation of 6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-a]pyridine To a mixture of 2-(4-fluorophenyl)pyrrolidine (201 mg, 1.22 mmol, 1.2 eq.) and 6-bromoimidazo[1,2- a]pyridine (200 mg, 1.02 mmol) in toluene (5.00 mL) was added Pd2(dba)3 (96 mg, 0.10 mmol, 0.10 eq.), XPhos (25 mg, 0.051 mmol, 0.05 eq.) and sodium tert-butoxide (199 mg, 2.03 mmol, 2
  • Step 3 Preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 47)
  • a mixture of 6-[2-(4-fluorophenyl)pyrrolidin-1-yl]-3-iodo-imidazo[1,2-a]pyridine 140 mg, 0.275 mmol, 1.00 eq.
  • methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate 94 mg, 0.33 mmol, 1.2 eq.
  • Potassium carbonate (76 mg, 0.55 mmol, 2.0 eq.) was added and the reaction mixture was degassed with argon for 5 minutes.
  • CataCXium® A Pd G3 (CAS 1651823-59-4, 10 mg, 0.014 mmol, 0.05 mmol) was added and the mixture was heated at 100°C for 1 hour under microwave irraditation. The mixture was cooled down, filtered through a pad of celite and washed with ethyl acetate. The filtrate was washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • Example 9 preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4- oxadiazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 10) (Compound 10) Step 1: Preparation of 2-chloro-N-(-4-fluoro-3-methoxy-phenyl)acetamide To a suspension of 4-fluoro-3-methoxy-aniline (10.0 g, 70.9 mmol) and potassium carbonate (10.8 g, 77.9 mmol, 1.10 eq.) in dimethylformamide (50.0 mL) at 0 °C was added, dropwise, a solution of 2- chloroacetyl chloride (8.80 g, 77.9 mmol, 1.00 eq.) in dimethylformamide (5.00 mL).
  • reaction mixture was stirred at room temperature for 3 hours, then it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford 2-chloro-N-(4-fluoro-3-methoxy- phenyl)acetamide as a colorless oil.
  • reaction mixture was warmed to room temperature and stirred for an additional 3 hours, after which it was poured into ice water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford N-(2-chloroethyl)-4- fluoro-3-methoxy-aniline as a colorless liquid.
  • reaction mixture was concentrated to dryness under reduced pressure and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford ethyl 3- bromoimidazo[1,2-a]pyridine-6-carboximidate as white solid.
  • Example 10 preparation of methyl N-[5-[6-[5-(4-fluorophenyl)-1-methyl-imidazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 23) (Compound 23) Step 1: Preparation of 5-(4-fluorophenyl)-1-methyl-imidazole To a solution of 1-bromo-4-fluoro-benzene (639 mg, 3.65 mmol, 1.50 eq.) and 1-methylimidazole (200 mg, 2.44 mmol, 1.00 eq.) in dry dimethylformamide (12.0 mL) was added tris(2-furyl)phosphane (57 mg, 0.24 mmol, 0.10 eq.), Pd(OAc)2 (27 mg, 0.12 mmol, 0.05 eq.) and potassium carbonate (673 mg, 4.87 mmol, 2.00 eq.).
  • reaction mixture was heated to 110 °C and stirred under a nitrogen atmosphere until full conversion.
  • the reaction mixture was then cooled, diluted with ethyl acetate/dichloromethane (25.0 mL, 1:1), filtered, and the filtrate was concentrated under reduced pressure.
  • the crude residue was purified by reverse phase chromatography (eluting with acetonitrile/water, from 10% to 90% containing 0.1% formic acid) to afford 5-(4-fluorophenyl)-1-methyl-imidazole as a white solid.
  • Step 2 Preparation of 4-bromo-5-(4-fluorophenyl)-1-methyl-imidazole
  • 5-(4-fluorophenyl)-1-methyl-imidazole 320 mg, 1.82 mmol
  • acetonitrile 4.00 mL
  • 1-bromopyrrolidine-2,5-dione 323 mg, 1.82 mmol, 1.00 eq.
  • the resulting solution was slowly warmed to room temperature and stirred for 16 hours. After the transformation was completed, the resulting mixture was diluted with water and extracted with ethyl acetate.
  • Step 3 Preparation of methyl N-[5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-pyridyl]carbamate
  • 6-bromo-3-iodo-imidazo[1,2-a]pyridine (4.00 g, 12.4 mmol) in dioxane/water (5/1; 42.0 mL) was added methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (4.13 g, 14.9 mmol), sodium carbonate (2.63 g, 24.8 mmol) and palladium tetrakistriphenylphosphine (1.43 g, 1.24 mmol) under an atmosphere of nitrogen .
  • Step 4 Preparation of [3-[6-(methoxycarbonylamino)-3-pyridyl]imidazo[1,2-a]pyridin-6-yl]boronic acid
  • methyl N-[5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-pyridyl]carbamate (3.00 g, 8.64 mmol) in dioxane (45.0 mL) was added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-1,3,2-dioxaborolane (3.29 g, 13.0 mmol), potassium acetate (1.70 g, 17.3 mmol), and Pd(dppf)Cl2 (0.316 g, 0.432 mmol) under an atmosphere of nitrogen .
  • Example 11 preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)oxazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 21) (Compound 21) Step 1: Preparation of 5-(4-fluoro-3-methoxy-phenyl)oxazole To a solution of 1-(isocyanomethylsulfonyl)-4-methyl-benzene (5.00 g, 25.6 mmol) in MeOH (50.0 mL) was added 4-fluoro-3-methoxy-benzaldehyde (5.92 g, 38.4 mmol, 1.50 eq.) and potassium carbonate (8.85 g, 64.0 mmol, 2.50 eq.).
  • Step 3 Preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)oxazol-4-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (Compound 21)
  • 4-bromo-5-(4-fluoro-3-methoxy-phenyl)oxazole 250 mg, 0.919 mmol
  • [3-[6-(methoxycarbonylamino)-3-pyridyl]imidazo[1,2-a]pyridin-6- yl]boronic acid (287 mg, 0.919 mmol, 1.00 eq.
  • potassium carbonate 317 mg, 2.30 mmol, 2.50 eq.
  • Pd(dppf)Cl2 67.0 mg, 0.092 mmol, 0.100 eq.
  • Example 12 preparation of methyl N-[5-[6-[5-(4-fluorophenyl)oxazol-4-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 63)
  • 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in MeOH (100 mL) was added 1- (isocyanomethylsulfonyl)-4-methylbenzene (23.6 g, 121 mmol, 1.50 eq.) and potassium carbonate (27.8 g, 201 mmol, 2.50 eq.).
  • reaction mixture was then heated at 75 °C and stirred for 16 hours, after which it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 5-(4-fluorophenyl)oxazole as a yellow solid.
  • Example 13 preparation of methyl N-[5-[6-[4-(4-fluorophenyl)oxazol-5-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 62) (Compound 62) Step 1: Preparation of 4-(4-fluorophenyl)oxazole To a solution of 2-bromo-1-(4-fluorophenyl)ethenone (10.0 g, 46.1 mmol) in formic acid (150 mL) at room temperature was added ammonium formate (11.0 g, 175 mmol, 3.80 eq.). The mixture was heated at 110 °C and stirred for 3 hours.
  • Step 2 Preparation of 6-(4-bromo-1-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine
  • 3-chloro-6-(1-methylpyrazol-3-yl)imidazo[1,2-a]pyridine 5.90 g, 25.4 mmol
  • 1-bromopyrrolidine-2,5-dione 4.51 g, 25.4 mmol
  • the resulting solution was warmed to room temperature and stirred for an addition 16 hours.
  • the resulting mixture was diluted with water and extracted with ethyl acetate.
  • Step 3 Preparation of 3-chloro-6-[4-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-3-yl]imidazo[1,2- a]pyridine
  • 6-(4-bromo-1-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine 800 mg, 2.57 mmol
  • 4-fluoro-3-methoxy-phenyl)boronic acid (436 mg, 2.57 mmol, 1.00 eq.)
  • potassium carbonate (887 mg, 6.42 mmol, 2.50 eq.
  • Pd(dppf)Cl2 188 mg, 0.257 mmol, 0.100 eq.
  • Example 15 preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 25) (Compound 25) Step 1: Preparation of methyl 8-methylimidazo[1,2-a]pyridine-6-carboxylate To a stirred solution of methyl 8-bromoimidazo[1,2-a]pyridine-6-carboxylate (500 mg, 1.76 mmol) and methylboronic acid (216 mg, 3.53 mmol) in THF was added potassium carbonate (488 mg, 3.53 mmol) and Pd(dppf)Cl2 (129 mg, 0.176 mmol), and the reaction mixture was degassed with argon for 2 min.
  • the reaction mixture was heated at 80 °C and stirred for 16 hours.
  • the reaction mixture was then cooled to room temperature, filtered through a pad of celite, and the filtrate was washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford methyl 8- methylimidazo[1,2-a]pyridine-6-carboxylate as an off white solid.
  • Step 2 Preparation of methyl 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxylate
  • acetonitrile 13 mL
  • N-bromosuccinimide 0.53 g, 2.9 mmol, 1.1 eq.
  • Step 4 Preparation of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxamide
  • THF 14 mL
  • dimethylformamide 0.1 mL
  • oxalyl chloride 584 mg, 4.51 mmol, 1.10 eq.
  • the reaction mixture was then cooled to room temperature, and an ammonium hydroxide solution (25% in water), (2.30 g, 16.4 mmol) was added dropwise.
  • Step 5 Preparation of (N)-3-bromo-N-(dimethylaminomethylene)-8-methyl-imidazo[1,2-a]pyridine-6- carboxamide
  • 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxamide (2.40 g, 8.97 mmol) in N.N-dimethylformamide dimethyl acetal (18.4 mL) was added acetic acid (1.13 g, 17.9 mmol, 2.00 eq.) and the reaction mixture was heated at 95 °C and stirred for 3 hours.
  • Step 6 Preparation of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridine
  • (N)-3-bromo-N-(dimethylaminomethylene)-8-methyl-imidazo[1,2-a]pyridine-6- carboxamide 300 mg, 0.922 mmol
  • dimethylformamide 3.00 mL
  • 4-fluoro-3-methoxy- phenyl)hydrazine hydrochloride 199 mg, 1.01 mmol, 1.10 eq.
  • the reaction mixture was heated at 95 °C and stirred for 3 hours before being slowly poured onto water.
  • Example 16 preparation of ethyl 3-(4-fluorophenyl)-2-[3-[6-(methoxycarbonylamino)-3- pyridyl]imidazo[1,2-a]pyridin-6-yl]imidazole-4-carboxylate (compound 67) (Compound 67) Step 1: Preparation of ethyl 3-(4-fluorophenyl)-2-iodo-imidazole-4-carboxylate To a stirred solution of ethyl 3-(4-fluorophenyl)imidazole-4-carboxylate (CAS 689250, commercially available and synthesis already described in ChemMedChem 2021, 16, 2195; 5.00 g, 21.3 mmol) in acetonitrile (80.0 mL) was added 1-iodopyrrolidine-2,5-dione (48.0 g, 213 mmol, 10.0 eq.) The reaction mixture was heated at 100 °C
  • Step 2 Preparation of ethyl 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carboxylate
  • ethyl 3-(4-fluorophenyl)-2-iodo-imidazole-4-carboxylate 200 mg, 0.544 mmol
  • imidazo[1,2-a]pyridin-6-ylboronic acid 176 mg, 1.09 mmol, 2.00 eq.
  • cesium carbonate 531 mg, 1.63 mmol, 3.00 eq.
  • reaction mixture was purged with argon for 10 minutes, then PdCl2(PPh3)2 (191 mg, 0.272 mmol, 0.500 eq.) was added and the resulting mixture heated at 100 °C and stirred for 2 hours under microwave irradiation microwave.
  • the reaction mixture was cooled, filtered through a pad of celite, the filtrate was diluted with water and extracted with ethyl acetate.
  • Step 3 Preparation of ethyl 3-(4-fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4- carboxylate
  • ethyl 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carboxylate 430 mg, 1.17 mmol
  • dimethylformamide 30.0 mL
  • 1-iodopyrrolidine-2,5-dione (289 mg, 1.28 mmol, 1.10 eq.
  • reaction mixture then was diluted with ice cold water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford ethyl 3-(4- fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4-carboxylate.
  • reaction mixture was purged with argon for 10 minutes, then cataCXium® A (7 mg, 0.02 mmol, 0.05 eq.) was added and the resulting reaction mixture was heated at 100 °C and stirred for 1 hour under microwave irradiation.
  • the rection mixture was cooled, filtered through a pad of celite, the filtrate was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Example 17 preparation of methyl N-[5-[6-[5-cyano-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 71) (Compound 71) Step 1: Preparation of 3-(4-fluorophenyl)imidazole-4-carboxamide A solution of ethyl 3-(4-fluorophenyl)imidazole-4-carboxylate (90.0 % purity, 100 mg, 0.384 mmol) in aqueous ammonia (67.3 mg, 1.92 mmol) in seal tube was heated at 120 °C and stirred for 24 hours.
  • Step 2 Preparation of 3-(4-fluorophenyl)imidazole-4-carbonitrile
  • THF 5.00 mL
  • pyridine 1.21 g, 15.4 mmo, 3.00 eq.
  • trifluoro acetic anhydride 1.61 g, 7.68 mmol, 1.50 eq.
  • Step 3 Preparation of 2-bromo-3-(4-fluorophenyl)imidazole-4-carbonitrile
  • 3-(4-fluorophenyl)imidazole-4-carbonitrile 310 mg, 1.62 mmol
  • 1-bromopyrrolidine-2,5-dione 1333 mg, 8.12 mmol
  • the resulting reaction mixture was heated at 120 °C and stirred for 6 hours in a seal tube.
  • the reaction mixture was then cooled and concentrated under reduced pressure, the crude residue was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 4 Preparation of 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carbonitrile
  • 2-bromo-3-(4-fluorophenyl)imidazole-4-carbonitrile 60.0 mg, 0.223 mmol
  • imidazo[1,2-a]pyridin-6-ylboronic acid 54 mg, 0.34 mmol, 1.5 eq.
  • cesium carbonate 145 mg, 0.447 mmol, 2.00 eq.
  • reaction mixture was purged with argon for 10 minutes, and then [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (18 mg, 0.23 mmol, 0.10 eq.) was added and the reaction was heated at 100 °C and stirred for 2 hours under microwave irradiation.
  • the reaction mixture was then cooled, filtered through at pad of celite, the filtrate was diluted with water and the aqueous layer extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 5 Preparation of 3-(4-fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4-carbonitrile
  • 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carbonitrile 180 mg, 0.588 mmol
  • 1-iodopyrrolidine-2,5-dione 145 mg, 0.646 mmol, 1.10 eq.
  • Step 6 Preparation of methyl N-[5-[6-[5-cyano-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 71)
  • 3-(4-fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4-carbonitrile 150 mg, 0.343 mmol
  • reaction mixture was purged with argon for 10 minutes and then cataCXium® A (6 mg, 0.017mmol, 0.050 eq.) was added and the resulting reaction mixture heated at 100 °C and stirred for 1 hour under microwave irradiation.
  • the reaction mixture was cooled to room temperature, filtered through a pad of celite, the filtrate was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • Example 18 preparation of methyl N-[5-[6-[3-(4-fluorophenyl)-5-methyl-imidazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 41) (Compound 41) Step 1: Preparation of 1-(4-fluorophenyl)-5-iodo-4-methyl-imidazole A solution of 1-(4-fluorophenyl)-4-methyl-imidazole (CAS 924709-34-2; synthesized as described in J. Org.
  • Step 2 Preparation of 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]imidazo[1,2-a]pyridine
  • 1-(4-fluorophenyl)-5-iodo-4-methyl-imidazole 250 mg, 0.786 mmol
  • imidazo[1,2- a]pyridin-6-ylboronic acid 153 mg, 0.943 mmol, 1.20 eq.
  • cesium carbonate 512 mg, 1.57 mmol, 2.00 eq.
  • Step 3 Preparation of 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]-3-iodo-imidazo[1,2-a]pyridine
  • a solution of 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]imidazo[1,2-a]pyridine (100 mg, 0.325 mmol) in dimethylformamide (5.00 mL) was charged with N-iodosuccinimide (80.4 mg, 0.357 mmol, 1.10 eq.) and the reaction mixture was stirred at room temperature for 16 hours. Afterwards it was diluted with water (20.0 mL) and extracted with ethyl acetate.
  • Step 4 Preparation of methyl N-[5-[6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 41)
  • 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]-3-iodo-imidazo[1,2-a]pyridine 8.0.0 mg, 0.182 mmol
  • reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (ethyl acetate/hexane) to afford the title compound, which was further purified by C-18 column chromatography (water/acetonitrile) to afford methyl N-[5-[6-[3-(4-fluorophenyl)-5-methyl-imidazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid.
  • Example 19 preparation of methyl N-[5-[6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 72) (Compound 72) Step 1: Preparation of 2-bromo-5-chloro-1-(4-fluorophenyl)imidazole To a solution of 5-chloro-1-(4-fluorophenyl)imidazole (synthesized as described in Science of Synthesis 2002, 12, 325-528; 250 mg, 1.08 mmol) in chloroform (5.00 mL) was added N-bromosuccinimide (226 mg, 1.24 mmol, 1.15 eq.), followed by 2-[(E)-(1-cyano-1-methyl-ethyl)azo]-2-methyl-propanenitrile (17.7 mg, 0.108 mmol, 0.100 eq.)
  • Step 2 Preparation of 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridine
  • 2-bromo-5-chloro-1-(4-fluorophenyl)imidazole 50.0 mg, 0.163 mmol
  • imidazo[1,2-a]pyridin-6-ylboronic acid 30 mg, 0.19 mmol, 1.15 eq.
  • reaction mixture was degassed with argon for 2 minutes, then Pd(dppf)Cl2 (12 mg, 0.016 mmol, 0.10 eq.) was added. The mixture was then heated to 100 °C under microwave irradiation for 45 min. After cooling to room temperature, the reaction mixture was filtered and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2- a]pyridine as a brown solid.
  • Step 3 Preparation of 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]-3-iodo-imidazo[1,2-a]pyridine
  • 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridine 160 mg, 0.435 mmol
  • dimethylformamide 5.00 mL
  • N-iodosuccinimide 108 mg, 0.478 mmol, 1.10 eq.
  • Example 20 preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol- 3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 26) (Compound 26) Step 1: Preparation of 3-bromoimidazo[1,2-a]pyridine-6-carbohydrazide To a solution of methyl 3-bromoimidazo[1,2-a]pyridine-6-carboxylate (1.00 g, 3.80 mmol) in methanol (5.43 mL) was added hydrazine hydrate (0.226 mL, 4.56 mmol, 1.20 eq.).
  • Step 2 Preparation of 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole
  • 3-bromoimidazo[1,2-a]pyridine-6-carbohydrazide 500 mg, 1.96 mmol
  • triethyl orthoacetate 3.67 mL, 19.6 mmol, 10.0 eq.
  • the reaction mixture was heated at 130 °C and stirred for 90 min.
  • the reaction mixture was cooled and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.359 mL, 2.35 mmol, 1.20 eq.) was added.
  • the reaction mixture was heated again at 130 °C and stirred for an additional 20 min.
  • Step 3 Preparation of 3-bromo-6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine
  • 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole 200 mg, 0.717 mmol
  • 4-fluoro-3-methoxyaniline 532 mg, 3.58 mmol, 5.00 eq.
  • reaction mixture was then cooled down to room temperature and slowly quenched with a saturated NaHCO3 solution.
  • aqueous phase was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the crude residue was purified by flash chromatography over silica gel (ethylacetate/EtOH/cyclohexane) to afford 3-bromo-6-[4-(4-fluoro- 3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine as a beige solid.
  • Step 4 Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 26)
  • 3-bromo-6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine 260 mg, 0.646 mmol
  • 2-methoxycarbonylaminopyridine-5-boronic acid pinacol ester (265 mg, 0.905 mmol, 1.40 eq.
  • cesium carbonate (319 mg, 0.970 mmol, 1.50 eq.
  • 2- methyltetrahydrofuran (8.40 mL)
  • water 2.80 mL
  • the reaction mixture was purged with argon and heated at 100 °C for 30 min under microwave irradiation.
  • the suspension was cooled to room temperature, petroleum ether was added, the suspension was filtered and successively washed with water and petroleum ether.
  • the precipitate was dissolved in chloroform at 50 °C and filtered.
  • the filtrate was concentrated to give methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate as a white solid.
  • the reaction mixture was degassed with argon for 5 minutes, then Pd(PPh3)4 (330 mg, 0.286 mmol, 0.100 eq.) was added and it was stirred under nitrogen at 100 °C for 16 hours.
  • the reaction mixture was then cooled down to room temperature, NaOH (2N, 5.00 mL) was added and stirring continued for 10 minutes.
  • the reaction mixture was extracted with ethyl acetate, the aqueous layer was acidified with aqueous HCl 1N and extracted again with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 2 Preparation of 4-chloro-5-(4-fluorophenyl)pyrimidine
  • a mixture of 5-(4-fluorophenyl)pyrimidin-4-ol (500 mg, 2.23 mmol) and phosphoryl trichloride (2.05 mL, 22.3 mmol, 10.0 eq.) was heated at 110 °C and stirred for 3 hours. The mixture was then cooled and concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with saturated NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 3 Preparation of 6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridine
  • 4-chloro-5-(4-fluorophenyl)pyrimidine 350 mg, 1.51 mmol
  • imidazo[1,2- a]pyridin-6-ylboronic acid 293 mg, 1.81 mmol, 1.20 eq.
  • cesium carbonate 984 mg, 3.02 mmol, 2.00 eq.
  • reaction mixture was degassed with argon for 2 minutes, then Pd(dppf)Cl2 (110 mg, 0.151 mmol, 0.100 eq.) was added and the reaction mixture was heated at 100 °C and stirred 1 hour under microwave irradiation. After cooling down to room temperature, the reaction mixture was filtered through a pad of celite which was further washed with ethyl acetate. The filtrate was washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 4 Preparation of 6-[5-(4-fluorophenyl)pyrimidin-4-yl]-3-iodo-imidazo[1,2-a]pyridine
  • 6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridine 100 mg, 0.310 mmol
  • dimethylformamide 2.00 mL
  • N-iodosuccinimide 76.7 mg, 0.341 mmol, 1.10 eq.
  • Step 5 Preparation of methyl N-[5-[6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 69)
  • 6-[5-(4-fluorophenyl)pyrimidin-4-yl]-3-iodo-imidazo[1,2-a]pyridine 200 mg, 0.432 mmol
  • methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate 153 mg, 0.541 mmol, 1.25 eq.
  • cesium carbonate 282 mg, 0.865 mmol, 2.00 eq.
  • reaction mixture was degassed with argon for 2 minutes, then [2-(2- aminophenyl)phenyl]-chloro-palladium;dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane (XPhosPdG2; 17.0 mg, 0.0216 mmol, 0.05 eq.) was added and the resulting reaction mixture was heated at 100 oC under microwave irradiation for 1 hour. The reaction mixture was then cooled to room temperature, filtered through a pad of celite which was further washed using ethyl acetate. The filtrate was extracted with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the reaction mixture was degassed with argon for 2 minutes, then Pd(PPh3)4 (132 mg, 0.114 mmol, 0.100 eq.) was added and it was heated at 100 °C and stirred for 16 hours. The reaction mixture was then cooled to room temperature, NaOH (2N, 2.00 mL) was added and stirring continued for 10 minutes. The reaction mixture was diluted with ethyl acetate, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The aqueous layer was acidified with 1N HCl and again extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 2 Preparation of 3-chloro-4-(4-fluorophenyl)pyridazine
  • a suspension of 4-(4-fluorophenyl)pyridazin-3-ol (230 mg, 1.09 mmol) in phosphoryl trichloride (0.996 mL, 10.9 mmol, 10.0 eq.) was heated at 110 °C for 6 hours.
  • the reaction mixture was then cooled to room temperature, concentrated under reduced pressure and the residue obtained was diluted with ethyl acetate.
  • the solution was washed with saturated aqueous NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 3 Preparation of 6-[4-(4-fluorophenyl)pyridazin-3-yl]imidazo[1,2-a]pyridine
  • 3-chloro-4-(4-fluorophenyl)pyridazine (2.25 g, 9.71 mmol)
  • reaction mixture was degassed with argon for 5 minutes, then Pd(dppf)Cl2 (710 mg, 0.971 mmol, 0.100 eq.) was added and the mixture was heated at 100 °C and stirred for 1 hour under microwave irradiation.
  • the reaction mixture was filtered through a pad of celite which was further washed with ethyl acetate. The filtrate was washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 4 Preparation of 6-[4-(4-fluorophenyl)pyridazin-3-yl]-3-iodo-imidazo[1,2-a]pyridine
  • 6-[4-(4-fluorophenyl)pyridazin-3-yl]imidazo[1,2-a]pyridine 500 mg, 1.60 mmol
  • dimethylformamide 5.00 mL
  • 1-iodopyrrolidine-2,5-dione 432 mg, 1.92 mmol, 1.20 eq.
  • the resulting mixture was stirred for 16 hours at room temperature and then poured into water.
  • Step 5 Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 70)
  • 6-[4-(4-fluorophenyl)pyridazin-3-yl]-3-iodo-imidazo[1,2-a]pyridine 150 mg, 0.324 mmol
  • methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate 115 mg, 0.405 mmol, 1.25 eq.
  • cesium carbonate 211 mg, 0.649 mmol, 2.00 eq.
  • CataCXium® A Pd G3 (24 mg, 0.032 mmol, 0.10 eq.) was added to the reaction mixture and it was heated at 100 oC and stirred for 1 hour under microwave irradiation. The reaction mixture was cooled and then filtered through a pad of celite which was further washed with ethyl acetate. The filtrate was extracted with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Example 23 preparation of methyl N-[5-[6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 28)
  • Step 2 Preparation of 6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridine
  • reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridine.
  • Step 3 Preparation of 6-[3-(4-fluorophenyl)pyrazin-2-yl]-3-iodo-imidazo[1,2-a]pyridine
  • Step 4 Preparation of methyl N-[5-[6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 28)
  • a solution of 6-[3-(4-fluorophenyl)pyrazin-2-yl]-3-iodo-imidazo[1,2-a]pyridine (200 mg, 0.471 mmol) in 1,4-dioxane/water (v/v 5:1, 30.0 mL) was purge with argon for 5 minutes and then methyl N-[5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (157 mg, 0.565 mmol, 1.20 eq.), cesium carbonate (307 mg, 0.942 mmol, 2.00 eq.) and cataCXium® A
  • reaction mixture was heated at 100 °C and stirred for 1 hour under microwave irradiation.
  • the reaction mixture was then cooled to room temperature, diluted with water and extracted with ethyl acetate The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • the crude residue was purified by flash chromatography over silica gel (ethyl acetate/n-hexane) to afford methyl N-[5-[6-[3-(4- fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid.
  • Example 24 preparation of methyl N-[5-[6-[2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 49) (Compound 49) Step 1: Preparation of 5-(4-fluorophenyl)-1-imidazo[1,2-a]pyridin-6-yl-pyrrolidin-2-one To a stirred solution of 5-(4-fluorophenyl)pyrrolidin-2-one (commercially available CAS 90432-58-9; 259 mg, 1.44 mmol, 1.20 eq.) and 6-bromoimidazo[1,2-a]pyridine (237 mg, 1.20 mmol) in dioxane (4.00 mL) was added copper(I) iodide (23 mg, 0.12 mmol, 0.10 eq.), potassium carbonate (333 mg, 2.41 mmol, 2.00
  • reaction mixture was stirred overnight at 100 °C, then it was cooled down to room temperature, diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water twice and once with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 5-(4-fluorophenyl)- 1-imidazo[1,2-a]pyridin-6-yl-pyrrolidin-2-one.
  • Step 2 Preparation of 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5-(4-fluorophenyl)pyrrolidin-2-one
  • 5-(4-fluorophenyl)-1-imidazo[1,2-a]pyridin-6-yl-pyrrolidin-2-one 210 mg, 0.711 mmol
  • N-bromosuccinimide 153 mg, 0.853 mmol, 1.20 eq.
  • Step 3 Preparation of methyl N-[5-[6-[2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 49)
  • a 25 mL vial containing methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2- pyridyl]carbamate (162 mg, 0.582 mmol, 1.10 eq.)
  • 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5- (4-fluorophenyl)pyrrolidin-2-one 198 mg, 0.5291 mmol
  • potassium carbonate 1 M in water (2.00 mL, 2.00 mmol, 3.78 eq.
  • 2-methyltetrahydrofuran (4.00 mL)
  • reaction mixture was degassed with argon and left to stir in a sealed tube heated at 80 °C for 2 hours.
  • the reaction mixture was then cooled and diethyl ether was added to the reaction mixture.
  • the resulting solid that formed was filtered, and further washed with diethyl ether to afford methyl N-[5-[6-[2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate.
  • Example 25 preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol- 3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 33) (Compound 33) Step 1: Preparation of 3-bromoimidazo[1,2-a]pyridine-6-carboxamide To a solution of 3-bromoimidazo[1,2-a]pyridine-6-carboxylic acid (430 mg, 1.69 mmol) in THF (5.65 mL) was added a drop of dimethylformamide followed by a slow addition of oxalyl chloride (0.159 mL, 1.78 mmol, 1.05 eq.).
  • reaction mixture was stirred for 40 minutes at 50 °C, and then ammonium hydroxide solution (28% in water, 0.848 mL, 6.78 mmol, 4.00 eq.) was added slowly and stirring continued for 30 minutes at 50 °C.
  • ammonium hydroxide solution (28% in water, 0.848 mL, 6.78 mmol, 4.00 eq.) was added slowly and stirring continued for 30 minutes at 50 °C.
  • the reaction mixture was cooled to room temperature, ice was added, the precipitate that formed was filtered, and washed with water to afford 3-bromoimidazo[1,2-a]pyridine-6-carboxamide as a white solid.
  • Step 2 Preparation of (NE)-3-bromo-N-[1-(dimethylamino)ethylidene]imidazo[1,2-a]pyridine-6- carboxamide
  • acetic acid 0.014 mL, 0.25 mmol, 0.20 eq.
  • Step 3 Preparation of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine
  • (NE)-3-bromo-N-[1-(dimethylamino)ethylidene]imidazo[1,2-a]pyridine-6-carboxamide 150 mg, 0.485 mmol
  • dimethylformamide 0.70 mL
  • 1-(4-fluoro-3- methoxyphenyl)hydrazine hydrochloride 118 mg, 0.582 mmol, 1.20 eq.
  • the reaction mixture was heated at 90 °C and stirred for 30 minutes, and then heated to 95 °C and stirred for an additional 3 hours.
  • the reaction mixture was cooled and then water was added and the mixture was extracted with ethyl acetate.
  • the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl- 1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine as a brown solid.
  • the product was used without further purification.
  • Step 4 Preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 33)
  • 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine 140 mg, 0.348 mmol
  • 2-methoxycarbonylaminopyridine-5-boronic acid pinacol ester 143 mg, 0.487 mmol, 1.43 eq.
  • cesium carbonate 172 mg, 0.522 mmol, 1.50 eq.
  • 2-methyltetrahydrofuran 4.5 mL
  • water 1.5 mL
  • the reaction mixture was purged with argon and heated at 100 °C for 30 min under microwave irradiation.
  • the solution was cooled to room temperature, water was added, and the solution was extracted with dichloromethane.
  • the combined organic layers were washed with brine, dried over sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography (dichloromethane/methanol) to afford methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a brown solid.
  • Example 26 preparation of methyl N-[5-[6-[1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 43)
  • copper(I) chloride 113 mg, 1.12 mmol, 0.100 eq.
  • potassium carbonate (1.64 g, 11.8 mmol, 1.05 eq.)
  • acetylacetone (0.290 mL, 2.80 mmol, 0.250 eq.) and NMP (2.24 mL) was added under argon imidazole (924 mg, 13.4 mmol, 1.20 eq.) and 1-bromo-4- fluorobenzene (1.26 mL, 11.2 mmol).
  • the reaction mixture was heated at 120 °C and stirred. The reaction mixture was then cooled down to room temperature, mixed with saturated aqueous NaHCO3 solution and dichloromethane and stirred for 15 minutes at room temperature. The suspension was filtered through a pad of celite, and the filtrate was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/ethanol) to afford 1-(4-fluorophenyl)imidazole as a yellow liquid.
  • Step 2 Preparation of 3-bromo-6-[1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridine
  • 1-(4-fluorophenyl)imidazole 300 mg, 1.85 mmol
  • THF 2.50 mL
  • n-buthyllithium in hexane 2.50 mol/L, 0.890 mL, 2.22 mmol, 1.20 eq.
  • the reaction mixture was heated at 100 °C and stirred overnight, then it was cooled to room temperature and stirred in a mixture of saturated aqueous NaHCO3 solution and ethyl acetate for 20 minutes. The mixture was then extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (cyclohexane/ethyl acetate/ethanol) to afford 3-bromo-6-[1-(4-fluorophenyl)imidazol-2- yl]imidazo[1,2-a]pyridine as a yellow solid.
  • Step 3 Preparation of methyl N-[5-[6-[1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 43)
  • 3-bromo-6-[1-(4-fluorophenyl) imidazol-2-yl]imidazo[1,2-a]pyridine 80.0 mg, 0.220 mmol
  • 2-methyltetrahydrofuran (2.90 mL) water (0.970 mL) and tetrakis(triphenylphosphine) palladium(0) (13.0 mg, 0.011 mmol, 0.0500 eq
  • the reaction mixture was purged with argon and heated at 100 °C for 30 minutes under microwave irradiation.
  • the solution was cooled to room temperature, water was added, and the solution was extracted with ethyl acetate.
  • the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • the crude residue was purified by flash chromatography over silica gel (dichloromethane/methanol) to afford methyl N-[5-[6-[1-(4- fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a white solid.
  • Example 27 preparation of methyl N-[5-[6-[5-cyano-2-(4-fluorophenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 74) (Compound 74) Step 1: Preparation of dimethyl 2-[(3-bromoimidazo[1,2-a]pyridine-6-carbonyl)amino]propanedioate To a solution of 3-bromoimidazo[1,2-a]pyridine-6-carboxylic acid (500 mg, 2.03 mmol) in ethyl acetate (8.13 mL) was added dimethyl aminomalonate hydrochloride (500 mg, 2.64 mmol, 1.30 eq.) followed by N,N-diisopropylethylamine (1.79 mL, 10.2 mmol, 5.00 eq.) and propylphosphonic anhydride in e
  • Step 2 Preparation of methyl 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4-triazole-3- carboxylate
  • sodium nitrite (112 mg, 1.62 mmol, 1.20 eq.) in water (0.794 mL) was added dropwise to a mixture of 4-fluoroaniline (182 mg, 1.62 mmol, 1.20 eq.) and conc. HCl (0.397 mL) in acetic acid (1.17 mL) at 0 °C.
  • Step 3 Preparation of 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4-triazole-3-
  • methyl 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4- triazole-3-carboxylate 100 mg, 0.240 mmol
  • ammonia in methanol (6.90 mL).
  • the reaction mixture was stirred for 5 minutes at 80 °C and then 1 additional hour at room temperature. The volatiles were removed under reduced pressure and the residue was solubilized in dichloromethane (1.60 mL).
  • Triethylamine (0.101 mL, 0.721 mmol, 3.00 eq.) was added to the solution, followed by a slow addition of trifluoro acetic anhydride (0.0675 mL, 0.481 mmol, 2.00 eq.).
  • the reaction mixture was stirred for 30 minutes at room temperature, then it was quenched with a saturated aqueous NaHCO 3 solution and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure.
  • Step 4 Preparation of methyl N-[5-[6-[5-cyano-2-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 74)
  • 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4- triazole-3-carbonitrile (65.0 mg, 0.170 mmol) followed by 2-methoxycarbonylaminopyridine-5-boronic acid, pinacol ester (70.0 mg, 0.240 mmol, 1.40 eq.), cesium carbonate (84.0 mg, 0.250 mmol, 1.50 eq.), 2-methyltetrahydrofuran (2.20 mL), water (0.730 mL) and tetrakis(triphenylphosphine) palladium(0) (10 mg
  • the reaction mixture was purged with argon and heated at 100 °C for 30 minutes under microwave irradiation.
  • the solution was cooled to room temperature, water was added, and the solution was extracted with ethyl acetate.
  • the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • Example 28 preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 4) (Compound 4) Step 1: Preparation of (NE)-3-bromo-N-(dimethylaminomethylene)imidazo[1,2-a]pyridine-6- carboxamide To a suspension of 3-bromoimidazo[1,2-a]pyridine-6-carboxamide (see synthetic example 25, step 1; 0.82 g, 3.41 mmol) in N,N-dimethylformamide dimethyl acetal (0.623 g, 0.695 mL, 5.12 mmol) was added acetic acid (0.041 g, 0.039 mL, 0.683 mmol).
  • Step 2 Preparation of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridine (Intermediate I-1) (Intermediate I-1) To a solution of (NE)-3-bromo-N-(dimethylaminomethylene)imidazo[1,2-a]pyridine-6-carboxamide (750 mg, 2.54 mmol) in dimethylformamide (25.4 mL) was added 1-(4-fluoro-3-methoxyphenyl)hydrazine hydrochloride (618 mg, 3.05 mmol, 1.20 eq.). The reaction mixture was heated at 90 °C and stirred overnight.
  • Step 3 Preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 4)
  • 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridine (Intermediate I-1, 785 mg, 1.92 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-2-pyridyl]carbamate (748 mg, 2.69 mmol, 1.40 eq.) were dissolved in 2- methyltetrahydrofuran (11.5 mL) and water (3.84 mL).
  • Example 29 preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 75) (Compound 75) Step 1: Preparation of 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole N To 3-bromoimidazo[1,2-a]pyridine-6-carbohydrazide (see synthetic example 20, step 1; 360 mg, 1.41 mmol) was added triethyl orthoformate (2.40 mL, 14.1 mmol, 10.0 eq.) and the reaction mixture was stirred overnight at 140 °C.
  • Step 2 Preparation of 3-bromo-6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine
  • 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole 160 mg, 0.604 mmol
  • 4-fluoroaniline 0.289 mL, 3.02 mmol, 5.00 eq.
  • the reaction mixture was heated at 120 °C and stirred for 4 hours, then it was cooled down to room temperature, saturated aqueous aq.
  • Step 3 Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 75)
  • 3-bromo-6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine 90.0 mg, 0.251 mmol
  • 2-methoxycarbonylaminopyridine-5-boronic acid pinacol ester 101 mg, 0.352 mmol, 1.40 eq.
  • Example 30 preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 76)
  • methyl 3-bromoimidazo[1,2-a]pyridine-6-carboxylate (1.00 g, 3.84 mmol) and N,O- dimethylhydroxylamine hydrochloride (574 mg, 5.76 mmol, 1.50 eq.) in THF (12.8 mL) at 0 °C under argon was added methyl magnesium bromide in methyltetrahydrofuran (5.40 mL, 17.3 mmol).
  • Step 2 Preparation of 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-3-(dimethylamino)prop-2-en-1-one
  • acetic acid 0.0053 mL, 0.092 mmol, 0.2 eq.
  • Step 3 Preparation of 3-bromo-6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridine
  • 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-3-(dimethylamino)prop-2-en-1-one 130 mg, 0.442 mmol
  • 4-fluorophenylhydrazine hydrochloride 89 mg, 0.53 mmol, 1.2 eq.
  • Step 4 Preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 76)
  • 3-bromo-6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridine 110 mg, 0.308 mmol
  • 2-methoxycarbonylaminopyridine-5-boronic acid pinacol ester 124 mg, 0.431 mmol, 1.40 eq.
  • cesium carbonate 152 mg, 0.462 mmol, 1.5 eq.
  • 1,4-dioxane (9.2 mL), water (3.1 mL) and tetrakis(triphenylphosphine) palladium(0) (18.0 mg, 0.0154 mmol, 0.0500 eq.).
  • the reaction mixture was purged with argon and heated at 100 °C under microwave irradiation for 30 minutes. The reaction mixture was then cooled, water was added and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/methanol) to afford methyl N-[5-[6-[2-(4-fluorophenyl)pyrazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a beige solid.
  • Example 31 preparation of methyl N-[5-[6-[4-(4-fluoro-3-methyl-phenyl)-5-methyl-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 5)
  • a solution of 2-amino-5-bromo-3-methylpyridine (2.0 g, 10.7 mmol) in ethanol (42.8 mL) was stirred under nitrogen atmosphere. Then chloroacetaldehyde solution (2.33 g, 13.37 mmol, 1.89 mL, 1.25 eq.) was added.
  • the bomb was then flushed with carbon monoxide, sealed, and pressurized to 2.5 MPa with carbon monoxide.
  • the reaction was stirred at 100 °C for 8 hours.
  • the vessel was then cooled to room temperature and the pressure released.
  • the reaction mixture was concentrated to dryness and purified by silica gel column chromatography (eluting with dichloromethane/MeOH) to obtain the methyl 8-methylimidazo[1,2- a]pyridine-6-carboxylate as a brown solid.
  • Step 3 Preparation of methyl 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxylate
  • acetonitrile 13 mL
  • N-bromosuccinimide 0.53 g, 2.9 mmol, 1.1 eq.
  • Step 5 Preparation of 2-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole (Intermediate I-3) (Intermediate I-3) A mixture of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carbohydrazide (Intermediate I-2, 9.4 g, 35 mmol) and triethyl orthoacetate (58 g, 65 mL, 350 mmol, 10 eq.) was stirred for 3 hours at 130 °C.1,8- diazabicyclo[5.4.0]undec-7-ene (6.5 g, 6.4 mL, 42 mmol, 1.2 eq.) was then added.
  • Step 6 Preparation of 5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin- 2-amine
  • 2-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole (Intermediate I-3, 0.34 g, 1.16 mmol)
  • 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2- amine 0.383 g, 1.74 mmol, 1.50 eq.
  • reaction mixture was stirred at room temperature overnight.
  • the reaction mixture was concentrated under reduced pressure and purified by flash chromatography on neutral alumina (eluting 15-20% methanol in ethyl acetate) to afford methyl N-[5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate.
  • the aqueous layer was extracted ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • the crude residue was purified over a silica gel cartridge (cyclohexane/ethyl acetate, 3:2) to afford methyl 8-cyclopropylimidazo[1,2-a]pyridine-6-carboxylate as brown solid.
  • the reaction mixture was stirred for overnight at 120 °C.
  • the reaction mixture was cooled down to room temperature and then water was added.
  • the aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • the crude residue was purified over a silica gel cartridge (eluting cyclohexane/ethyl acetate, 3:7) to afford 2-(8-cyclopropylimidazo[1,2-a]pyridin-6-yl)- 1,3,4-oxadiazole as white solid.
  • the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with sodium thiosulphate pentahydrate, dried over sodium sulfate, filtered, and concentrated under reduced pressure.
  • the crude was purified by flash chromatography over silical gel (eluting cyclohexane/ethyl acetate, 8:2) to afford ethyl acetate 2-(3-bromo-8-cyclopropyl-imidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole as a yellow solid.
  • reaction mixture was stirred at 80 °C for 16 hours. The reaction mixture was then concentrated under reduced pressure. Saturated aqueous NaHCO3 and dichloromethane were added. The aqueous layer was extracted with dichloromethane, the combined organic phases were dried with sodium sulfate, filtered and concentrated under reduced pressure. The residual was purified by silica gel column chromatography (eluting with ethyl acetate/petroleum ether, 0% to 75%) to afford 6-iodo-8-methyl-imidazo[1,2-a]pyridine as a yellow solid.
  • Example 36 Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4- oxadiazin-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 3) (Compound 3) Step 1: Preparation of 8-methylimidazo[1,2-a]pyridine-6-carbonitrile To a solution of 6-iodo-8-methyl-imidazo[1,2-a]pyridine (Intermediate I-4, 17.0 g, 59.3 mmol), zinc cyanide (13.9 g, 119 mmol, 2 eq.) and 1,1'-bis(diphenylphosphino)ferrocene (3.29 g, 5.93 mmol, 0.10 eq.) in dimethylformamide (300 mL) was added Pd2(dba)3 (2.71
  • reaction mixture was stirred at 120 °C for 3 hours under nitrogen. After being cooled to room temperature, the reaction mixture was diluted with water and the mixture was filtered through celite. The filtrate was extracted with ethyl acetate, the combined organic layers were washed with water and brine, dried with sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel column chromatography (eluting with dichloromethane/MeOH, 2% to 5%) to provide 8-methylimidazo[1,2-a]pyridine-6-carbonitrile as a brown solid.
  • reaction mixture was stirred at room temperature for 3 hours, then it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silical gel (petroleum ether/ethyl acetate) to afford 2-chloro-N-(4-fluoro-3-methoxy- phenyl)acetamide as a colorless oil.
  • reaction mixture was warmed to room temperature and stirred for an additional 3 hours, after which it was poured into ice water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford N-(2-chloroethyl)-4- fluoro-3-methoxy-aniline as a colorless liquid.
  • Example 37 Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]- 8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 1) (Compound 1) Step 1: Preparation of N-(2-chloroethyl)-4-fluoro-aniline To a solution of 4-fluoroaniline (2.00 g, 18.0 mmol) in a mixture of methanol (30 mL) and acetic acid (1.03 mL, 18.0 mmol, 1.00 eq.) at room temperature was added portionwise sodium cyanoborohydride (1.79 g, 27.0 mmol, 1.50 eq.) followed by 2-chloroacetaldehyde (2.59 mL, 21.6 mmol, 1.20 eq.).
  • Example 38 Preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 9) (Compound 9) Step 1: Preparation of 2-chloro-5-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]pyridine A solution of 4-fluoro-3-methoxy-benzamide (1.60 g, 9.46 mmol) in 1,1-dimethoxy-N,N-dimethyl- methanamine (8.00 mL) was heated at 100 °C for 2 hours.
  • the mixture was concentrated under reduced pressure. The residue was taken up in acetic acid (16.0 mL), and (6-chloro-3-pyridyl)hydrazine (1.36 g, 9.46 mmol, 1.00 eq.) was added. Then the mixture was heated at 95 °C for 3 hours. The reaction mixture was then concentrated under vacuum. The mixture was adjusted to pH 7 with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum.
  • Example 39 Preparation of 5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]pyridin-2-amine
  • a solution of sodium carbonate (12.9 mg, 0.122 mmol, 3.05 eq.) in water (0.200 mL) was added to 2- aminopyridine-5-boronic acid pinacol ester (14.1 mg, 0.0638 mmol, 1.60 eq.), followed by addition of a solution of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine (Intermediate I-1, 15.5 mg, 0.0400 mmol) in acetonitrile (0.200 mL).
  • the leaf disks are inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf disks are incubated at 16 °C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).
  • the following compounds gave at least 80% control of Phytophthora infestans at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 77, 80, 81, 85, 86, 87, 90, 92, 95, 101, 104, 107, 108, 111, 112.
  • Grape vine leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water.
  • the leaf disks are inoculated with a spore suspension of the fungus 1 day after application.
  • the inoculated leaf disks are incubated at 19 °C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 - 8 days after application).
  • test compound After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal mycelia/spore mixture is added. The test plates are incubated at 24 °C and the inhibition of growth is determined photometrically 2-3 days after application.
  • DMSO DMSO
  • the following compounds gave at least 80% control of Pythium ultimum at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 48, 49, 50, 51, 53, 54, 55, 56, 57, 61, 65, 68, 69, 70, 71, 75, 76, 77, 79, 80, 85, 86, 87, 90, 92, 95, 104, 107, 109, 112, 113.

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Abstract

The current invention relates to compounds of the formula (I), wherein the substituents are as defined in claim 1, to processes and methods for preparing compounds of formula (I), to agrochemical compositions comprising compounds of formula (I) as defined in claim 1, to preparation of these compositions and to the use of the compounds or compositions in agriculture or horticulture for combating, preventing or controlling infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, in particular fungi.

Description

Imidazo[1,2-a]pyridine derivatives The present invention relates to microbiocidal imidazo[1,2-a]pyridine derivatives, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity, more particularly activity against oomycetes. The invention also relates to preparation of these imidazo[1,2-a]pyridine derivatives, to intermediates useful in the preparation of these imidazo[1,2-a]pyridine derivatives, to the preparation of these intermediates, to agrochemical compositions which comprise at least one of the imidazo[1,2- a]pyridine derivatives, to preparation of these compositions and to the use of the imidazo[1,2-a]pyridine derivatives or compositions in agriculture or horticulture for combating, controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, in particular fungi, more particularly oomycetes. It has now surprisingly been found that certain novel imidazo[1,2-a]pyridine derivatives have favourable fungicidal properties, in particular against oomycetes. Therefore, in a first aspect, the present invention provides compounds of formula (I) 2b
Figure imgf000002_0001
a 5-8-membered heterocycle, a 6-12-membered aromatic ring or a 5-11-membered heteroaromatic ring, wherein each of the 5-8-membered carbocycle, the 5-8-membered heterocycle, the 6-12-membered aromatic ring or the 5-11-membered heteroaromatic ring is optionally substituted with one to four substituents independently selected from R1; A is CH or N; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than four A3 are N, preferably no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, hydroxy, amino, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1- 6alkylaminocarbonyl and diC1-6alkylaminocarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; and wherein optionally two geminal R1 taken together with the carbon they are attached to form a carbonyl group; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, C1-6alkylcarbonyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1- 6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, and C1-6alkylcarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; and R6 is selected from C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1- 6alkylamino, diC1-6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino, wherein each of the C1- 6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1-6alkylamino, diC1- 6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino groups is optionally substituted with one to three substituents independently selected from halogen and CN; or a salt or N-oxide thereof. In a second aspect the present invention provides an agrochemical composition comprising a compound of formula (I), and more particularly an agrochemical composition comprising a fungicidally effective amount of a compound of formula (I). Said composition can further comprise at least one compound selected among an additional active ingredient, an appropriate formulation inert, a carrier, an adjuvant, and any mixtures thereof. Compounds of formula (I) may be used to control phytopathogenic microorganisms. Thus, in order to control a phytopathogen a compound of formula (I), or a composition comprising a compound of formula (I) according to the invention, may be applied directly to the phytopathogen, to the locus of a phytopathogen, in particular to a plant susceptible to attack by phytopathogens, or to a propagation material of a plant. Thus, in a third aspect the present invention provides the use of a compound of formula (I), or a composition comprising a compound of formula (I), as described herein to combat, prevent or control a phytopathogen. In a fourth aspect the present invention provides a method of combating, preventing or controlling phytopathogens, comprising applying a compound of formula (I), or a composition comprising a compound of formula (I), as described herein to said phytopathogen, to the locus of said phytopathogen, in particular to a plant susceptible to attack by a phytopathogen, or to a propagation material of a plant. Compounds of formula (I) are particularly effective in combating, preventing or controlling phytopathogenic fungi, in particular oomycetes. Thus, in a fifth aspect the present invention provides the use of a compound of formula (I), or a composition comprising a compound of formula (I), as described herein to control phytopathogenic fungi, in particular oomycetes. In a sixth aspect the present invention provides a method of combating, preventing or controlling phytopathogenic disease, such as phytopathogenic fungi, comprising applying a compound of formula (I), or a composition comprising a compound of formula (I), as described herein to said phytopathogenic fungi, or to the locus of said phytopathogenic fungi, in particular to a plant susceptible to attack by phytopathogenic fungi, in particular oomycetes, or to a propagation material of a plant. Where a group is indicated as being substituted, e.g. alkyl, this includes those groups that are part of other groups, e.g. the alkyl in alkylthio. Definitions: - The term "halogen" refers to fluorine (fluoro or F), chlorine (chloro or Cl), bromine (bromo or Br) or iodine (iodo or I), preferably fluorine, chlorine or bromine. - The term "Alkyl" as used herein- in isolation or as part of a chemical group – represents straight-chain or branched hydrocarbons, preferably with 1 to 6 carbon atoms, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, pentyl, 1- methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2- dimethylpropyl, 1,1 -dimethylpropyl, 2,2- dimethylpropyl, 1 -ethylpropyl, hexyl, 1 -methylpentyl, 2- methylpentyl, 3-methylpentyl, 4- methylpentyl, 1,2-dimethylpropyl, 1,3-dimethylbutyl, 1,4-dimethylbutyl, 2,3-dimethylbutyl, 1,1- dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-trimethylpropyl, 1,2,2- trimethylpropyl, 1- ethylbutyl and 2-ethylbutyl. Alkyl groups with 1 to 4 carbon atoms are preferred, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl or t-butyl. - The term "Alkenyl" - in isolation or as part of a chemical group - represents straight-chain or branched hydrocarbons, preferably with 2 to 6 carbon atoms and at least one double bond, for example vinyl, 2- propenyl, 2-butenyl, 3-butenyl, 1- methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl, 4- pentenyl, 1-methyl-2-butenyl, 2- methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3- butenyl, 3-methyl-3-butenyl, 1,1 - dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 1 -ethyl-2-propenyl, 2- hexenyl, 3-hexenyl, 4- hexenyl, 5-hexenyl, 1 -methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2- pentenyl, 4-methyl-2- pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1 -methyl-4-pentenyl, 2- methyl-4-pentenyl, 3- methyl-4-pentenyl, 4-methyl-4-pentenyl, 1, 1 -dimethyl-2-butenyl, 1,1-dimethyl-3- butenyl, 1,2- dimethyl-2-butenyl, l,2-dimethyl-3-butenyl, 1,3-dimethyl-2-butenyl, 2,2-dimethyl-3-butenyl, 2,3- dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 1 -ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1, 1,2-trimethyl-2-propenyl, 1 -ethyl- 1 -methyl-2-propenyl und 1-ethyl-2-methyl-2- propenyl. Alkenyl groups with 2 to 4 carbon atoms are preferred, for example 2-propenyl, 2-butenyl or 1-methyl-2-propenyl. - The term "Alkynyl" - in isolation or as part of a chemical group - represents straight-chain or branched hydrocarbons, preferably with 2 to 6 carbon atoms and at least one triple bond, for example 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2- propynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-3-butynyl, 2- methyl-3-butynyl, 1-methyl-2- butynyl, 1,1 -dimethyl-2-propynyl, 1 -ethyl-2-propynyl, 2-hexynyl, 3- hexynyl, 4-hexynyl, 5-hexynyl, 1- methyl-2-pentynyl, 1-methyl-3-pentynyl, 1 -methyl-4-pentynyl, 2- methyl-3-pentynyl, 2-methyl-4- pentynyl, 3 -methyl-4-pentynyl, 4-methyl-2-pentynyl, 1,1 -dimethyl-3 - butynyl, 1,2-dimethyl-3 –butynyl, 2,2- dimethyl-3-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1- methyl-2-propynyl and 2,5-hexadiynyl. Alkynyls with 2 to 4 carbon atoms are preferred, for example ethynyl, 2- propynyl or 2-butynyl-2-propenyl. - The term "cycloalkyl" - in isolation or as part of a chemical group - represents saturated or partially unsaturated mono-, bi- or tricyclic hydrocarbons, preferably with 3 to 10 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl or adamantyl. Cycloalkyls with 3, 4, 5, 6 or 7 carbon atoms are preferred, for example cyclopropyl or cyclobutyl. - The term “alkoxy" refers to a radical of the formula -ORa wherein Ra is an alkyl radical as generally defined above. Examples of alkoxy include, but are not limited to methoxy, ethoxy, propoxy, iso-propoxy, and tert-butoxy. - The term “ alkylsulfanyl” refers to a radical of the formula -SRa wherein Ra is an alkyl radical as generally defined above. - The term “alkylsulfinyl” refers to a radical of the formula -S(O)Ra wherein Ra is an alkyl radical as generally defined above. - The term “alkylsulfonyl” refers to a radical of the formula -S(O)2Ra wherein Ra is an alkyl radical as generally defined above. - the term “alkoxycarbonyl” refers to a radical of the formula RaOC(O)-, wherein Ra is an alkyl radical as generally defined above. - The term “alkylaminocarbonyl” refers to a radical of the formula RaNHC(O)- wherein Ra is an alkyl radical as generally defined above. - Hydroxyl or hydroxy stands for a –OH group. The term ”combating”, “preventing” or “controlling”, and its inflections, within the context of the present invention, mean reducing any undesired effect, such as pathogenic and more particularly phytopathogenic, especially fungi such as oomycetes, infestation or attack of, and pathogenic damage to a plant or to a plant derived product to such a level that an improvement is demonstrated. As used herein, the term "effective amount" refers to the amount of the compound, a salt, or N-oxide thereof, which, upon single or multiple applications provides the desired effect. An effective amount is readily determined by the skilled person in the art, by the use of known techniques and by observing results obtained under analogous circumstances. In determining the effective amount a number of factors are considered including, but not limited to: the type of plant or derived product to be applied; the pathogen to be controlled & its lifecycle; the particular compound applied; the type of application; and other relevant circumstances. Compounds of formula (I) which have at least one basic centre can form, for example, acid addition salts, for example with strong inorganic acids such as mineral acids, for example perchloric acid, sulfuric acid, nitric acid, nitrous acid, a phosphorus acid or a hydrohalic acid, with strong organic carboxylic acids, such as C1-C4alkanecarboxylic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid, or with organic sulfonic acids, such as C1-C4alkane- or arylsulfonic acids which are unsubstituted or substituted, for example by halogen, for example methane- or p-toluenesulfonic acid. Compounds of formula (I) which have at least one acidic group can form, for example, salts with bases, for example mineral salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or dimethylpropylamine, or a mono-, di- or trihydroxy-lower-alkylamine, for example mono-, di- or triethanolamine. In each case, the compounds of formula (I) according to the invention are in free form, in oxidized form as an N-oxide, in covalently hydrated form, or in salt form, e.g., an agronomically usable or agrochemically acceptable salt form. N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N-oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991. The compounds of formula (I) according to the invention also include hydrates, which may be formed during salt formation. The compounds of formula (I) according to the invention also include hydrates which may be formed during the salt formation. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein four A3 are CR4 and one A3 is N. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein , and preferably the four A3 are CR4.
Figure imgf000007_0001
In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein 3 , and preferably the four A3 are CR4.
Figure imgf000007_0002
In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein the five A3 are CR4. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein A1 is a carbon atom and A2 is a nitrogen atom. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein A1 is a carbon atom and A2 is a carbon atom. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein A1 is a nitrogen atom and A2 is a carbon atom. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein A1 is a nitrogen atom and A2 is a nitrogen atom. In a further embodiment, there is provided a compound of formula (I) according to the present invention, wherein ring W * selected from:
Figure imgf000007_0003
, , group , the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1- 4alkyl, C2-6alkenyl and C2-6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN. Ring W can be optionally substituted with one to four substituents independently selected from R1 as defined in the present invention. More preferably, ring W *
Figure imgf000008_0001
wherein * represents the point of attachment to the imidazopyridine group in formula (I), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is as defined in the present invention. Ring W can be optionally substituted with one to four substituents independently selected from R1 as defined in the present invention. In a particular embodiment, there is provided a compound of formula (I) according to the present invention, wherein ring W is a 5-8-membered heterocycle or a 5-11-membered heteroaromatic ring, wherein each of the 5- 8-membered heterocycle or the 5-11-membered heteroaromatic ring is optionally substituted with one to four substituents independently selected from R1, A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; * and more preferably selected from:
Figure imgf000009_0001
Figure imgf000009_0002
wherein * represents the point of attachment to the imidazopyridine group in formula (I), and # represents the point of attachment to the ring formed by the A3 groups, ring W being optionally substituted with one to four substituents independently selected from R1 as defined in the present invention, and wherein R11 is as defined in the present invention;A is N; A3 are independently CR4 or N, with the proviso that no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C1- 6alkoxy, and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl- C1-4alkyl, and C1-6alkoxy groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; R2a, R2b and R2c are independently selected from hydrogen, halogen, CN, C1-6alkyl, C3-6cycloalkyl, C1- 6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkoxy, and -NHC(O)C1-6alkyl;preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl- C1-4alkyl, and C1-6alkoxy; and preferably R2a and R2c are hydrogen and R2b is selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, and C1-6alkoxy; R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2- 6alkynyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-6alkyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; preferably R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, halogen, C3- 6cycloalkyl, and C3-6cycloalkyl-C1-6alkyl, wherein each of the C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C3-6cycloalkyl, and C3-6cycloalkyl-C1-6alkyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; and more preferably R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, CN, and halogen, wherein each of the C1-6alkyl and C1-6alkoxy groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; and R6 is selected from C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl and C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, wherein each of the C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl and C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl groups is optionally substituted with one to three substituents independently selected from halogen and CN; and preferably R6 is selected from C1-6alkyl and C1-6alkoxy, wherein each of the C1-6alkyl and C1- 6alkoxy groups is optionally substituted with one to three substituents independently selected from halogen and CN. In a further embodiment, the compound according to the present invention is selected from: methyl N-[5-[6-[4-(4-fluorophenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate; methyl N-[5-[8-cyclopropyl-6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methyl-phenyl)-5-methyl-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-5-methyl-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[1-(4-fluoro-3-methoxy-phenyl)imidazol-2-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate; methyl N-[5-[6-[1-(4-fluoro-3-methoxy-phenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methyl-phenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(3,4-difluorophenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate; methyl N-[5-[8-cyclopropyl-6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[2-(3,4-difluorophenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[1-(4-fluorophenyl)imidazol-2-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)oxazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-imidazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluorophenyl)-1-methyl-imidazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[2-(4-chloro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-oxo-1,2,4-oxadiazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methyl-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[2-(3,4-difluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluorophenyl)-1,3-dimethyl-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1H-pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-1-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-5-methyl-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methyl-phenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(3,4-difluorophenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[(2R)-2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-imidazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluorophenyl)-5-methyl-imidazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-2-methyl-imidazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluorophenyl)-2-methyl-imidazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluorophenyl)-1-methyl-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)pyrazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluorophenyl)pyrazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)oxazol-5-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)isoxazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)oxazol-5-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluorophenyl)oxazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)isoxazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-5-oxo-1,2,4-oxadiazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; ethyl 3-(4-fluorophenyl)-2-[3-[6-(methoxycarbonylamino)-3-pyridyl]imidazo[1,2-a]pyridin-6-yl]imidazole- 4-carboxylate; methyl N-[5-[6-[(2R)-2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[5-cyano-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-chloro-2-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[5-cyano-2-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate; methyl N-[5-[6-[4-(3,4-difluorophenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(6-methoxy-3-pyridyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; N-[4-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-2-methoxy- acetamide; N-[4-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]phenyl]cyclopropanecarboxamide; 1-ethyl-3-[4-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]urea; 3-[4-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-1,1-dimethyl- urea; benzyl N-[4-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; 1-ethyl-3-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]urea; N-[4-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]acetamide; N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]cyclopropanecarboxamide; methyl N-[4-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; tert-butyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; tert-butyl N-[4-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]acetamide; methyl N-[5-[6-[5-(3-fluoro-4-methylsulfonyl-phenyl)-1-methyl-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]acetamide; tert-butyl N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; methyl N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; tert-butyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate; N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]acetamide; benzyl N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; 3-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-1,1-dimethyl- urea; 1-ethyl-3-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]urea; N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3- yl]phenyl]cyclopropanecarboxamide; N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]phenyl]-2-methoxy- acetamide; 1-ethyl-3-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]urea; N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]acetamide; tert-butyl N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; tert-butyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate; methyl N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]acetamide; benzyl N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate; 3-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]phenyl]- 1,1-dimethyl-urea; 1-ethyl-3-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]urea; N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]cyclopropanecarboxamide; N-[4-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]phenyl]-2- methoxy-acetamide; and 1-ethyl-3-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]urea. The method according to the present invention has advantageous properties for protecting plants against pathogenic, such as phytopathogenic, especially fungi such as oomycetes, attack or infestation, which result in a disease and damage to the plant; particularly in instance of plants, the present invention can control, limit or prevent pathogenic damage on plant, parts of plant, plant propagation material and/or plant grown. The compounds in Tables 1.1 to 1.162 below illustrate the compounds of the invention. Table 1.1 provides compounds E1.1 to E1.1078 of formula (I-1)
Figure imgf000016_0001
wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents
Figure imgf000016_0002
the point of attachment to the imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Each of Tables 1.2 to 1.162 (which follow Table 1.1) discloses individual compounds of the formula (I- 1) in which A, R2a, R2c, R6 and ring W are specifically defined in Tables 1.2 to 1.162, which refer to Table Z wherein A3a, A3b, R2b, R4 are specifically defined. Table Z: Substituent definitions of A3a, A3b, R2b and R4 Compound A3b R2b R4 A3a E1.1 CH H H CH E1.2 CH H CH3 CH E1.3 CH H CH2CH3 CH E1.4 CH H F CH E1.5 CH H Cl CH E1.6 CH H Br CH E1.7 CH H CN CH E1.8 CH H OCH3 CH E1.9 CH H OCH2CH3 CH E1.10 CH H OCH2CH2OCH3 CH E1.11 CH H OH CH E1.12 CH CH3 H CH E1.13 CH CH3 CH3 CH E1.14 CH CH3 CH2CH3 CH E1.15 CH CH3 F CH E1.16 CH CH3 Cl CH E1.17 CH CH3 Br CH E1.18 CH CH3 CN CH E1.19 CH CH3 OCH3 CH E1.20 CH CH3 OCH2CH3 CH E1.21 CH CH3 OCH2CH2OCH3 CH Compound A3b R2b R4 A3a E1.22 CH CH3 OH CH E1.23 CH CH2CH3 H CH E1.24 CH CH2CH3 CH3 CH E1.25 CH CH2CH3 CH2CH3 CH E1.26 CH CH2CH3 F CH E1.27 CH CH2CH3 Cl CH E1.28 CH CH2CH3 Br CH E1.29 CH CH2CH3 CN CH E1.30 CH CH2CH3 OCH3 CH E1.31 CH CH2CH3 OCH2CH3 CH E1.32 CH CH2CH3 OCH2CH2OCH3 CH E1.33 CH CH2CH3 OH CH E1.34 CH CH2OCH3 H CH E1.35 CH CH2OCH3 CH3 CH E1.36 CH CH2OCH3 CH2CH3 CH E1.37 CH CH2OCH3 F CH E1.38 CH CH2OCH3 Cl CH E1.39 CH CH2OCH3 Br CH E1.40 CH CH2OCH3 CN CH E1.41 CH CH2OCH3 OCH3 CH E1.42 CH CH2OCH3 OCH2CH3 CH E1.43 CH CH2OCH3 OCH2CH2OCH3 CH E1.44 CH CH2OCH3 OH CH E1.45 CH CH2CN H CH E1.46 CH CH2CN CH3 CH E1.47 CH CH2CN CH2CH3 CH E1.48 CH CH2CN F CH E1.49 CH CH2CN Cl CH E1.50 CH CH2CN Br CH E1.51 CH CH2CN CN CH E1.52 CH CH2CN OCH3 CH E1.53 CH CH2CN OCH2CH3 CH E1.54 CH CH2CN OCH2CH2OCH3 CH E1.55 CH CH2CN OH CH E1.56 CH H CH E1.57 CH CH3 CH E1.58 CH CH2CH3 CH E1.59 CH F CH E1.60 CH Cl CH E1.61 CH Br CH Compound A3b R2b R4 A3a E1.62 CH CN CH E1.63 CH OCH3 CH E1.64 CH OCH2CH3 CH E1.65 CH OCH2CH2OCH3 CH E1.66 CH OH CH E1.67 CH NHAc H CH E1.68 CH NHAc CH3 CH E1.69 CH NHAc CH2CH3 CH E1.70 CH NHAc F CH E1.71 CH NHAc Cl CH E1.72 CH NHAc Br CH E1.73 CH NHAc CN CH E1.74 CH NHAc OCH3 CH E1.75 CH NHAc OCH2CH3 CH E1.76 CH NHAc OCH2CH2OCH3 CH E1.77 CH NHAc OH CH E1.78 N H H CH E1.79 N H CH3 CH E1.80 N H CH2CH3 CH E1.81 N H F CH E1.82 N H Cl CH E1.83 N H Br CH E1.84 N H CN CH E1.85 N H OCH3 CH E1.86 N H OCH2CH3 CH E1.87 N H OCH2CH2OCH3 CH E1.88 N H OH CH E1.89 N CH3 H CH E1.90 N CH3 CH3 CH E1.91 N CH3 CH2CH3 CH E1.92 N CH3 F CH E1.93 N CH3 Cl CH E1.94 N CH3 Br CH E1.95 N CH3 CN CH E1.96 N CH3 OCH3 CH E1.97 N CH3 OCH2CH3 CH E1.98 N CH3 OCH2CH2OCH3 CH E1.99 N CH3 OH CH E1.100 N CH2CH3 H CH E1.101 N CH2CH3 CH3 CH E1.102 N CH2CH3 CH2CH3 CH Compound A3b R2b R4 A3a E1.103 N CH2CH3 F CH E1.104 N CH2CH3 Cl CH E1.105 N CH2CH3 Br CH E1.106 N CH2CH3 CN CH E1.107 N CH2CH3 OCH3 CH E1.108 N CH2CH3 OCH2CH3 CH E1.109 N CH2CH3 OCH2CH2OCH3 CH E1.110 N CH2CH3 OH CH E1.111 N CH2OCH3 H CH E1.112 N CH2OCH3 CH3 CH E1.113 N CH2OCH3 CH2CH3 CH E1.114 N CH2OCH3 F CH E1.115 N CH2OCH3 Cl CH E1.116 N CH2OCH3 Br CH E1.117 N CH2OCH3 CN CH E1.118 N CH2OCH3 OCH3 CH E1.119 N CH2OCH3 OCH2CH3 CH E1.120 N CH2OCH3 OCH2CH2OCH3 CH E1.121 N CH2OCH3 OH CH E1.122 N CH2CN H CH E1.123 N CH2CN CH3 CH E1.124 N CH2CN CH2CH3 CH E1.125 N CH2CN F CH E1.126 N CH2CN Cl CH E1.127 N CH2CN Br CH E1.128 N CH2CN CN CH E1.129 N CH2CN OCH3 CH E1.130 N CH2CN OCH2CH3 CH E1.131 N CH2CN OCH2CH2OCH3 CH E1.132 N CH2CN OH CH E1.133 N H CH E1.134 N CH3 CH E1.135 N CH2CH3 CH E1.136 N F CH E1.137 N Cl CH E1.138 N Br CH E1.139 N CN CH E1.140 N OCH3 CH Compound A3b R2b R4 A3a E1.141 N OCH2CH3 CH E1.142 N OCH2CH2OCH3 CH E1.143 N OH CH E1.144 N NHAc H CH E1.145 N NHAc CH3 CH E1.146 N NHAc CH2CH3 CH E1.147 N NHAc F CH E1.148 N NHAc Cl CH E1.149 N NHAc Br CH E1.150 N NHAc CN CH E1.151 N NHAc OCH3 CH E1.152 N NHAc OCH2CH3 CH E1.153 N NHAc OCH2CH2OCH3 CH E1.154 N NHAc OH CH E1.155 CH H H N E1.156 CH H CH3 N E1.157 CH H CH2CH3 N E1.158 CH H F N E1.159 CH H Cl N E1.160 CH H Br N E1.161 CH H CN N E1.162 CH H OCH3 N E1.163 CH H OCH2CH3 N E1.164 CH H OCH2CH2OCH3 N E1.165 CH H OH N E1.166 CH CH3 H N E1.167 CH CH3 CH3 N E1.168 CH CH3 CH2CH3 N E1.169 CH CH3 F N E1.170 CH CH3 Cl N E1.171 CH CH3 Br N E1.172 CH CH3 CN N E1.173 CH CH3 OCH3 N E1.174 CH CH3 OCH2CH3 N E1.175 CH CH3 OCH2CH2OCH3 N E1.176 CH CH3 OH N E1.177 CH CH2CH3 H N E1.178 CH CH2CH3 CH3 N E1.179 CH CH2CH3 CH2CH3 N E1.180 CH CH2CH3 F N E1.181 CH CH2CH3 Cl N E1.182 CH CH2CH3 Br N Compound A3b R2b R4 A3a E1.183 CH CH2CH3 CN N E1.184 CH CH2CH3 OCH3 N E1.185 CH CH2CH3 OCH2CH3 N E1.186 CH CH2CH3 OCH2CH2OCH3 N E1.187 CH CH2CH3 OH N E1.188 CH CH2OCH3 H N E1.189 CH CH2OCH3 CH3 N E1.190 CH CH2OCH3 CH2CH3 N E1.191 CH CH2OCH3 F N E1.192 CH CH2OCH3 Cl N E1.193 CH CH2OCH3 Br N E1.194 CH CH2OCH3 CN N E1.195 CH CH2OCH3 OCH3 N E1.196 CH CH2OCH3 OCH2CH3 N E1.197 CH CH2OCH3 OCH2CH2OCH3 N E1.198 CH CH2OCH3 OH N E1.199 CH CH2CN H N E1.200 CH CH2CN CH3 N E1.201 CH CH2CN CH2CH3 N E1.202 CH CH2CN F N E1.203 CH CH2CN Cl N E1.204 CH CH2CN Br N E1.205 CH CH2CN CN N E1.206 CH CH2CN OCH3 N E1.207 CH CH2CN OCH2CH3 N E1.208 CH CH2CN OCH2CH2OCH3 N E1.209 CH CH2CN OH N E1.210 CH H N E1.211 CH CH3 N E1.212 CH CH2CH3 N E1.213 CH F N E1.214 CH Cl N E1.215 CH Br N E1.216 CH CN N E1.217 CH OCH3 N E1.218 CH OCH2CH3 N E1.219 CH OCH2CH2OCH3 N Compound A3b R2b R4 A3a E1.220 CH OH N E1.221 CH NHAc H N E1.222 CH NHAc CH3 N E1.223 CH NHAc CH2CH3 N E1.224 CH NHAc F N E1.225 CH NHAc Cl N E1.226 CH NHAc Br N E1.227 CH NHAc CN N E1.228 CH NHAc OCH3 N E1.229 CH NHAc OCH2CH3 N E1.230 CH NHAc OCH2CH2OCH3 N E1.231 CH NHAc OH N E1.232 N H H N E1.233 N H CH3 N E1.234 N H CH2CH3 N E1.235 N H F N E1.236 N H Cl N E1.237 N H Br N E1.238 N H CN N E1.239 N H OCH3 N E1.240 N H OCH2CH3 N E1.241 N H OCH2CH2OCH3 N E1.242 N H OH N E1.243 N CH3 H N E1.244 N CH3 CH3 N E1.245 N CH3 CH2CH3 N E1.246 N CH3 F N E1.247 N CH3 Cl N E1.248 N CH3 Br N E1.249 N CH3 CN N E1.250 N CH3 OCH3 N E1.251 N CH3 OCH2CH3 N E1.252 N CH3 OCH2CH2OCH3 N E1.253 N CH3 OH N E1.254 N CH2CH3 H N E1.255 N CH2CH3 CH3 N E1.256 N CH2CH3 CH2CH3 N E1.257 N CH2CH3 F N E1.258 N CH2CH3 Cl N E1.259 N CH2CH3 Br N E1.260 N CH2CH3 CN N E1.261 N CH2CH3 OCH3 N E1.262 N CH2CH3 OCH2CH3 N E1.263 N CH2CH3 OCH2CH2OCH3 N Compound A3b R2b R4 A3a E1.264 N CH2CH3 OH N E1.265 N CH2OCH3 H N E1.266 N CH2OCH3 CH3 N E1.267 N CH2OCH3 CH2CH3 N E1.268 N CH2OCH3 F N E1.269 N CH2OCH3 Cl N E1.270 N CH2OCH3 Br N E1.271 N CH2OCH3 CN N E1.272 N CH2OCH3 OCH3 N E1.273 N CH2OCH3 OCH2CH3 N E1.274 N CH2OCH3 OCH2CH2OCH3 N E1.275 N CH2OCH3 OH N E1.276 N CH2CN H N E1.277 N CH2CN CH3 N E1.278 N CH2CN CH2CH3 N E1.279 N CH2CN F N E1.280 N CH2CN Cl N E1.281 N CH2CN Br N E1.282 N CH2CN CN N E1.283 N CH2CN OCH3 N E1.284 N CH2CN OCH2CH3 N E1.285 N CH2CN OCH2CH2OCH3 N E1.286 N CH2CN OH N E1.287 N H N E1.288 N CH3 N E1.289 N CH2CH3 N E1.290 N F N E1.291 N Cl N E1.292 N Br N E1.293 N CN N E1.294 N OCH3 N E1.295 N OCH2CH3 N E1.296 N OCH2CH2OCH3 N E1.297 N OH N E1.298 N NHAc H N E1.299 N NHAc CH3 N E1.300 N NHAc CH2CH3 N E1.301 N NHAc F N E1.302 N NHAc Cl N Compound A3b R2b R4 A3a E1.303 N NHAc Br N E1.304 N NHAc CN N E1.305 N NHAc OCH3 N E1.306 N NHAc OCH2CH3 N E1.307 N NHAc OCH2CH2OCH3 N E1.308 N NHAc OH N E1.309 CH H H CF E1.310 CH H CH3 CF E1.311 CH H CH2CH3 CF E1.312 CH H F CF E1.313 CH H Cl CF E1.314 CH H Br CF E1.315 CH H CN CF E1.316 CH H OCH3 CF E1.317 CH H OCH2CH3 CF E1.318 CH H OCH2CH2OCH3 CF E1.319 CH H OH CF E1.320 CH CH3 H CF E1.321 CH CH3 CH3 CF E1.322 CH CH3 CH2CH3 CF E1.323 CH CH3 F CF E1.324 CH CH3 Cl CF E1.325 CH CH3 Br CF E1.326 CH CH3 CN CF E1.327 CH CH3 OCH3 CF E1.328 CH CH3 OCH2CH3 CF E1.329 CH CH3 OCH2CH2OCH3 CF E1.330 CH CH3 OH CF E1.331 CH CH2CH3 H CF E1.332 CH CH2CH3 CH3 CF E1.333 CH CH2CH3 CH2CH3 CF E1.334 CH CH2CH3 F CF E1.335 CH CH2CH3 Cl CF E1.336 CH CH2CH3 Br CF E1.337 CH CH2CH3 CN CF E1.338 CH CH2CH3 OCH3 CF E1.339 CH CH2CH3 OCH2CH3 CF E1.340 CH CH2CH3 OCH2CH2OCH3 CF E1.341 CH CH2CH3 OH CF E1.342 CH CH2OCH3 H CF E1.343 CH CH2OCH3 CH3 CF E1.344 CH CH2OCH3 CH2CH3 CF E1.345 CH CH2OCH3 F CF E1.346 CH CH2OCH3 Cl CF E1.347 CH CH2OCH3 Br CF Compound A3b R2b R4 A3a E1.348 CH CH2OCH3 CN CF E1.349 CH CH2OCH3 OCH3 CF E1.350 CH CH2OCH3 OCH2CH3 CF E1.351 CH CH2OCH3 OCH2CH2OCH3 CF E1.352 CH CH2OCH3 OH CF E1.353 CH CH2CN H CF E1.354 CH CH2CN CH3 CF E1.355 CH CH2CN CH2CH3 CF E1.356 CH CH2CN F CF E1.357 CH CH2CN Cl CF E1.358 CH CH2CN Br CF E1.359 CH CH2CN CN CF E1.360 CH CH2CN OCH3 CF E1.361 CH CH2CN OCH2CH3 CF E1.362 CH CH2CN OCH2CH2OCH3 CF E1.363 CH CH2CN OH CF E1.364 CH H CF E1.365 CH CH3 CF E1.366 CH CH2CH3 CF E1.367 CH F CF E1.368 CH Cl CF E1.369 CH Br CF E1.370 CH CN CF E1.371 CH OCH3 CF E1.372 CH OCH2CH3 CF E1.373 CH OCH2CH2OCH3 CF E1.374 CH OH CF E1.375 CH NHAc H CF E1.376 CH NHAc CH3 CF E1.377 CH NHAc CH2CH3 CF E1.378 CH NHAc F CF E1.379 CH NHAc Cl CF E1.380 CH NHAc Br CF E1.381 CH NHAc CN CF E1.382 CH NHAc OCH3 CF E1.383 CH NHAc OCH2CH3 CF E1.384 CH NHAc OCH2CH2OCH3 CF E1.385 CH NHAc OH CF E1.386 N H H CF Compound A3b R2b R4 A3a E1.387 N H CH3 CF E1.388 N H CH2CH3 CF E1.389 N H F CF E1.390 N H Cl CF E1.391 N H Br CF E1.392 N H CN CF E1.393 N H OCH3 CF E1.394 N H OCH2CH3 CF E1.395 N H OCH2CH2OCH3 CF E1.396 N H OH CF E1.397 N CH3 H CF E1.398 N CH3 CH3 CF E1.399 N CH3 CH2CH3 CF E1.400 N CH3 F CF E1.401 N CH3 Cl CF E1.402 N CH3 Br CF E1.403 N CH3 CN CF E1.404 N CH3 OCH3 CF E1.405 N CH3 OCH2CH3 CF E1.406 N CH3 OCH2CH2OCH3 CF E1.407 N CH3 OH CF E1.408 N CH2CH3 H CF E1.409 N CH2CH3 CH3 CF E1.410 N CH2CH3 CH2CH3 CF E1.411 N CH2CH3 F CF E1.412 N CH2CH3 Cl CF E1.413 N CH2CH3 Br CF E1.414 N CH2CH3 CN CF E1.415 N CH2CH3 OCH3 CF E1.416 N CH2CH3 OCH2CH3 CF E1.417 N CH2CH3 OCH2CH2OCH3 CF E1.418 N CH2CH3 OH CF E1.419 N CH2OCH3 H CF E1.420 N CH2OCH3 CH3 CF E1.421 N CH2OCH3 CH2CH3 CF E1.422 N CH2OCH3 F CF E1.423 N CH2OCH3 Cl CF E1.424 N CH2OCH3 Br CF E1.425 N CH2OCH3 CN CF E1.426 N CH2OCH3 OCH3 CF E1.427 N CH2OCH3 OCH2CH3 CF E1.428 N CH2OCH3 OCH2CH2OCH3 CF E1.429 N CH2OCH3 OH CF E1.430 N CH2CN H CF E1.431 N CH2CN CH3 CF Compound A3b R2b R4 A3a E1.432 N CH2CN CH2CH3 CF E1.433 N CH2CN F CF E1.434 N CH2CN Cl CF E1.435 N CH2CN Br CF E1.436 N CH2CN CN CF E1.437 N CH2CN OCH3 CF E1.438 N CH2CN OCH2CH3 CF E1.439 N CH2CN OCH2CH2OCH3 CF E1.440 N CH2CN OH CF E1.441 N H CF E1.442 N CH3 CF E1.443 N CH2CH3 CF E1.444 N F CF E1.445 N Cl CF E1.446 N Br CF E1.447 N CN CF E1.448 N OCH3 CF E1.449 N OCH2CH3 CF E1.450 N OCH2CH2OCH3 CF E1.451 N OH CF E1.452 N NHAc H CF E1.453 N NHAc CH3 CF E1.454 N NHAc CH2CH3 CF E1.455 N NHAc F CF E1.456 N NHAc Cl CF E1.457 N NHAc Br CF E1.458 N NHAc CN CF E1.459 N NHAc OCH3 CF E1.460 N NHAc OCH2CH3 CF E1.461 N NHAc OCH2CH2OCH3 CF E1.462 N NHAc OH CF E1.463 CH H H CCl E1.464 CH H CH3 CCl E1.465 CH H CH2CH3 CCl E1.466 CH H F CCl E1.467 CH H Cl CCl E1.468 CH H Br CCl E1.469 CH H CN CCl E1.470 CH H OCH3 CCl Compound A3b R2b R4 A3a E1.471 CH H OCH2CH3 CCl E1.472 CH H OCH2CH2OCH3 CCl E1.473 CH H OH CCl E1.474 CH CH3 H CCl E1.475 CH CH3 CH3 CCl E1.476 CH CH3 CH2CH3 CCl E1.477 CH CH3 F CCl E1.478 CH CH3 Cl CCl E1.479 CH CH3 Br CCl E1.480 CH CH3 CN CCl E1.481 CH CH3 OCH3 CCl E1.482 CH CH3 OCH2CH3 CCl E1.483 CH CH3 OCH2CH2OCH3 CCl E1.484 CH CH3 OH CCl E1.485 CH CH2CH3 H CCl E1.486 CH CH2CH3 CH3 CCl E1.487 CH CH2CH3 CH2CH3 CCl E1.488 CH CH2CH3 F CCl E1.489 CH CH2CH3 Cl CCl E1.490 CH CH2CH3 Br CCl E1.491 CH CH2CH3 CN CCl E1.492 CH CH2CH3 OCH3 CCl E1.493 CH CH2CH3 OCH2CH3 CCl E1.494 CH CH2CH3 OCH2CH2OCH3 CCl E1.495 CH CH2CH3 OH CCl E1.496 CH CH2OCH3 H CCl E1.497 CH CH2OCH3 CH3 CCl E1.498 CH CH2OCH3 CH2CH3 CCl E1.499 CH CH2OCH3 F CCl E1.500 CH CH2OCH3 Cl CCl E1.501 CH CH2OCH3 Br CCl E1.502 CH CH2OCH3 CN CCl E1.503 CH CH2OCH3 OCH3 CCl E1.504 CH CH2OCH3 OCH2CH3 CCl E1.505 CH CH2OCH3 OCH2CH2OCH3 CCl E1.506 CH CH2OCH3 OH CCl E1.507 CH CH2CN H CCl E1.508 CH CH2CN CH3 CCl E1.509 CH CH2CN CH2CH3 CCl E1.510 CH CH2CN F CCl E1.511 CH CH2CN Cl CCl E1.512 CH CH2CN Br CCl E1.513 CH CH2CN CN CCl E1.514 CH CH2CN OCH3 CCl E1.515 CH CH2CN OCH2CH3 CCl Compound A3b R2b R4 A3a E1.516 CH CH2CN OCH2CH2OCH3 CCl E1.517 CH CH2CN OH CCl E1.518 CH H CCl E1.519 CH CH3 CCl E1.520 CH CH2CH3 CCl E1.521 CH F CCl E1.522 CH Cl CCl E1.523 CH Br CCl E1.524 CH CN CCl E1.525 CH OCH3 CCl E1.526 CH OCH2CH3 CCl E1.527 CH OCH2CH2OCH3 CCl E1.528 CH OH CCl E1.529 CH NHAc H CCl E1.530 CH NHAc CH3 CCl E1.531 CH NHAc CH2CH3 CCl E1.532 CH NHAc F CCl E1.533 CH NHAc Cl CCl E1.534 CH NHAc Br CCl E1.535 CH NHAc CN CCl E1.536 CH NHAc OCH3 CCl E1.537 CH NHAc OCH2CH3 CCl E1.538 CH NHAc OCH2CH2OCH3 CCl E1.539 CH NHAc OH CCl E1.540 N H H CCl E1.541 N H CH3 CCl E1.542 N H CH2CH3 CCl E1.543 N H F CCl E1.544 N H Cl CCl E1.545 N H Br CCl E1.546 N H CN CCl E1.547 N H OCH3 CCl E1.548 N H OCH2CH3 CCl E1.549 N H OCH2CH2OCH3 CCl E1.550 N H OH CCl E1.551 N CH3 H CCl E1.552 N CH3 CH3 CCl E1.553 N CH3 CH2CH3 CCl E1.554 N CH3 F CCl Compound A3b R2b R4 A3a E1.555 N CH3 Cl CCl E1.556 N CH3 Br CCl E1.557 N CH3 CN CCl E1.558 N CH3 OCH3 CCl E1.559 N CH3 OCH2CH3 CCl E1.560 N CH3 OCH2CH2OCH3 CCl E1.561 N CH3 OH CCl E1.562 N CH2CH3 H CCl E1.563 N CH2CH3 CH3 CCl E1.564 N CH2CH3 CH2CH3 CCl E1.565 N CH2CH3 F CCl E1.566 N CH2CH3 Cl CCl E1.567 N CH2CH3 Br CCl E1.568 N CH2CH3 CN CCl E1.569 N CH2CH3 OCH3 CCl E1.570 N CH2CH3 OCH2CH3 CCl E1.571 N CH2CH3 OCH2CH2OCH3 CCl E1.572 N CH2CH3 OH CCl E1.573 N CH2OCH3 H CCl E1.574 N CH2OCH3 CH3 CCl E1.575 N CH2OCH3 CH2CH3 CCl E1.576 N CH2OCH3 F CCl E1.577 N CH2OCH3 Cl CCl E1.578 N CH2OCH3 Br CCl E1.579 N CH2OCH3 CN CCl E1.580 N CH2OCH3 OCH3 CCl E1.581 N CH2OCH3 OCH2CH3 CCl E1.582 N CH2OCH3 OCH2CH2OCH3 CCl E1.583 N CH2OCH3 OH CCl E1.584 N CH2CN H CCl E1.585 N CH2CN CH3 CCl E1.586 N CH2CN CH2CH3 CCl E1.587 N CH2CN F CCl E1.588 N CH2CN Cl CCl E1.589 N CH2CN Br CCl E1.590 N CH2CN CN CCl E1.591 N CH2CN OCH3 CCl E1.592 N CH2CN OCH2CH3 CCl E1.593 N CH2CN OCH2CH2OCH3 CCl E1.594 N CH2CN OH CCl E1.595 N H CCl E1.596 N CH3 CCl E1.597 N CH2CH3 CCl Compound A3b R2b R4 A3a E1.598 N F CCl E1.599 N Cl CCl E1.600 N Br CCl E1.601 N CN CCl E1.602 N OCH3 CCl E1.603 N OCH2CH3 CCl E1.604 N OCH2CH2OCH3 CCl E1.605 N OH CCl E1.606 N NHAc H CCl E1.607 N NHAc CH3 CCl E1.608 N NHAc CH2CH3 CCl E1.609 N NHAc F CCl E1.610 N NHAc Cl CCl E1.611 N NHAc Br CCl E1.612 N NHAc CN CCl E1.613 N NHAc OCH3 CCl E1.614 N NHAc OCH2CH3 CCl E1.615 N NHAc OCH2CH2OCH3 CCl E1.616 N NHAc OH CCl E1.617 CH H H CCH3 E1.618 CH H CH3 CCH3 E1.619 CH H CH2CH3 CCH3 E1.620 CH H F CCH3 E1.621 CH H Cl CCH3 E1.622 CH H Br CCH3 E1.623 CH H CN CCH3 E1.624 CH H OCH3 CCH3 E1.625 CH H OCH2CH3 CCH3 E1.626 CH H OCH2CH2OCH3 CCH3 E1.627 CH H OH CCH3 E1.628 CH CH3 H CCH3 E1.629 CH CH3 CH3 CCH3 E1.630 CH CH3 CH2CH3 CCH3 E1.631 CH CH3 F CCH3 E1.632 CH CH3 Cl CCH3 E1.633 CH CH3 Br CCH3 E1.634 CH CH3 CN CCH3 E1.635 CH CH3 OCH3 CCH3 E1.636 CH CH3 OCH2CH3 CCH3 E1.637 CH CH3 OCH2CH2OCH3 CCH3 Compound A3b R2b R4 A3a E1.638 CH CH3 OH CCH3 E1.639 CH CH2CH3 H CCH3 E1.640 CH CH2CH3 CH3 CCH3 E1.641 CH CH2CH3 CH2CH3 CCH3 E1.642 CH CH2CH3 F CCH3 E1.643 CH CH2CH3 Cl CCH3 E1.644 CH CH2CH3 Br CCH3 E1.645 CH CH2CH3 CN CCH3 E1.646 CH CH2CH3 OCH3 CCH3 E1.647 CH CH2CH3 OCH2CH3 CCH3 E1.648 CH CH2CH3 OCH2CH2OCH3 CCH3 E1.649 CH CH2CH3 OH CCH3 E1.650 CH CH2OCH3 H CCH3 E1.651 CH CH2OCH3 CH3 CCH3 E1.652 CH CH2OCH3 CH2CH3 CCH3 E1.653 CH CH2OCH3 F CCH3 E1.654 CH CH2OCH3 Cl CCH3 E1.655 CH CH2OCH3 Br CCH3 E1.656 CH CH2OCH3 CN CCH3 E1.657 CH CH2OCH3 OCH3 CCH3 E1.658 CH CH2OCH3 OCH2CH3 CCH3 E1.659 CH CH2OCH3 OCH2CH2OCH3 CCH3 E1.660 CH CH2OCH3 OH CCH3 E1.661 CH CH2CN H CCH3 E1.662 CH CH2CN CH3 CCH3 E1.663 CH CH2CN CH2CH3 CCH3 E1.664 CH CH2CN F CCH3 E1.665 CH CH2CN Cl CCH3 E1.666 CH CH2CN Br CCH3 E1.667 CH CH2CN CN CCH3 E1.668 CH CH2CN OCH3 CCH3 E1.669 CH CH2CN OCH2CH3 CCH3 E1.670 CH CH2CN OCH2CH2OCH3 CCH3 E1.671 CH CH2CN OH CCH3 E1.672 CH H CCH3 E1.673 CH CH3 CCH3 E1.674 CH CH2CH3 CCH3 E1.675 CH F CCH3 E1.676 CH Cl CCH3 E1.677 CH Br CCH3 E1.678 CH CN CCH3 Compound A3b R2b R4 A3a E1.679 CH OCH3 CCH3 E1.680 CH OCH2CH3 CCH3 E1.681 CH OCH2CH2OCH3 CCH3 E1.682 CH OH CCH3 E1.683 CH NHAc H CCH3 E1.684 CH NHAc CH3 CCH3 E1.685 CH NHAc CH2CH3 CCH3 E1.686 CH NHAc F CCH3 E1.687 CH NHAc Cl CCH3 E1.688 CH NHAc Br CCH3 E1.689 CH NHAc CN CCH3 E1.690 CH NHAc OCH3 CCH3 E1.691 CH NHAc OCH2CH3 CCH3 E1.692 CH NHAc OCH2CH2OCH3 CCH3 E1.693 CH NHAc OH CCH3 E1.694 N H H CCH3 E1.695 N H CH3 CCH3 E1.696 N H CH2CH3 CCH3 E1.697 N H F CCH3 E1.698 N H Cl CCH3 E1.699 N H Br CCH3 E1.700 N H CN CCH3 E1.701 N H OCH3 CCH3 E1.702 N H OCH2CH3 CCH3 E1.703 N H OCH2CH2OCH3 CCH3 E1.704 N H OH CCH3 E1.705 N CH3 H CCH3 E1.706 N CH3 CH3 CCH3 E1.707 N CH3 CH2CH3 CCH3 E1.708 N CH3 F CCH3 E1.709 N CH3 Cl CCH3 E1.710 N CH3 Br CCH3 E1.711 N CH3 CN CCH3 E1.712 N CH3 OCH3 CCH3 E1.713 N CH3 OCH2CH3 CCH3 E1.714 N CH3 OCH2CH2OCH3 CCH3 E1.715 N CH3 OH CCH3 E1.716 N CH2CH3 H CCH3 E1.717 N CH2CH3 CH3 CCH3 E1.718 N CH2CH3 CH2CH3 CCH3 E1.719 N CH2CH3 F CCH3 E1.720 N CH2CH3 Cl CCH3 Compound A3b R2b R4 A3a E1.721 N CH2CH3 Br CCH3 E1.722 N CH2CH3 CN CCH3 E1.723 N CH2CH3 OCH3 CCH3 E1.724 N CH2CH3 OCH2CH3 CCH3 E1.725 N CH2CH3 OCH2CH2OCH3 CCH3 E1.726 N CH2CH3 OH CCH3 E1.727 N CH2OCH3 H CCH3 E1.728 N CH2OCH3 CH3 CCH3 E1.729 N CH2OCH3 CH2CH3 CCH3 E1.730 N CH2OCH3 F CCH3 E1.731 N CH2OCH3 Cl CCH3 E1.732 N CH2OCH3 Br CCH3 E1.733 N CH2OCH3 CN CCH3 E1.734 N CH2OCH3 OCH3 CCH3 E1.735 N CH2OCH3 OCH2CH3 CCH3 E1.736 N CH2OCH3 OCH2CH2OCH3 CCH3 E1.737 N CH2OCH3 OH CCH3 E1.738 N CH2CN H CCH3 E1.739 N CH2CN CH3 CCH3 E1.740 N CH2CN CH2CH3 CCH3 E1.741 N CH2CN F CCH3 E1.742 N CH2CN Cl CCH3 E1.743 N CH2CN Br CCH3 E1.744 N CH2CN CN CCH3 E1.745 N CH2CN OCH3 CCH3 E1.746 N CH2CN OCH2CH3 CCH3 E1.747 N CH2CN OCH2CH2OCH3 CCH3 E1.748 N CH2CN OH CCH3 E1.749 N H CCH3 E1.750 N CH3 CCH3 E1.751 N CH2CH3 CCH3 E1.752 N F CCH3 E1.753 N Cl CCH3 E1.754 N Br CCH3 E1.755 N CN CCH3 E1.756 N OCH3 CCH3 E1.757 N OCH2CH3 CCH3 E1.758 N OCH2CH2OCH3 CCH3 E1.759 N OH CCH3 Compound A3b R2b R4 A3a E1.760 N NHAc H CCH3 E1.761 N NHAc CH3 CCH3 E1.762 N NHAc CH2CH3 CCH3 E1.763 N NHAc F CCH3 E1.764 N NHAc Cl CCH3 E1.765 N NHAc Br CCH3 E1.766 N NHAc CN CCH3 E1.767 N NHAc OCH3 CCH3 E1.768 N NHAc OCH2CH3 CCH3 E1.769 N NHAc OCH2CH2OCH3 CCH3 E1.770 N NHAc OH CCH3 E1.771 CH H H CCH2CH3 E1.772 CH H CH3 CCH2CH3 E1.773 CH H CH2CH3 CCH2CH3 E1.774 CH H F CCH2CH3 E1.775 CH H Cl CCH2CH3 E1.776 CH H Br CCH2CH3 E1.777 CH H CN CCH2CH3 E1.778 CH H OCH3 CCH2CH3 E1.779 CH H OCH2CH3 CCH2CH3 E1.780 CH H OCH2CH2OCH3 CCH2CH3 E1.781 CH H OH CCH2CH3 E1.782 CH CH3 H CCH2CH3 E1.783 CH CH3 CH3 CCH2CH3 E1.784 CH CH3 CH2CH3 CCH2CH3 E1.785 CH CH3 F CCH2CH3 E1.786 CH CH3 Cl CCH2CH3 E1.787 CH CH3 Br CCH2CH3 E1.788 CH CH3 CN CCH2CH3 E1.789 CH CH3 OCH3 CCH2CH3 E1.790 CH CH3 OCH2CH3 CCH2CH3 E1.791 CH CH3 OCH2CH2OCH3 CCH2CH3 E1.792 CH CH3 OH CCH2CH3 E1.793 CH CH2CH3 H CCH2CH3 E1.794 CH CH2CH3 CH3 CCH2CH3 E1.795 CH CH2CH3 CH2CH3 CCH2CH3 E1.796 CH CH2CH3 F CCH2CH3 E1.797 CH CH2CH3 Cl CCH2CH3 E1.798 CH CH2CH3 Br CCH2CH3 E1.799 CH CH2CH3 CN CCH2CH3 E1.800 CH CH2CH3 OCH3 CCH2CH3 E1.801 CH CH2CH3 OCH2CH3 CCH2CH3 E1.802 CH CH2CH3 OCH2CH2OCH3 CCH2CH3 E1.803 CH CH2CH3 OH CCH2CH3 E1.804 CH CH2OCH3 H CCH2CH3 Compound A3b R2b R4 A3a E1.805 CH CH2OCH3 CH3 CCH2CH3 E1.806 CH CH2OCH3 CH2CH3 CCH2CH3 E1.807 CH CH2OCH3 F CCH2CH3 E1.808 CH CH2OCH3 Cl CCH2CH3 E1.809 CH CH2OCH3 Br CCH2CH3 E1.810 CH CH2OCH3 CN CCH2CH3 E1.811 CH CH2OCH3 OCH3 CCH2CH3 E1.812 CH CH2OCH3 OCH2CH3 CCH2CH3 E1.813 CH CH2OCH3 OCH2CH2OCH3 CCH2CH3 E1.814 CH CH2OCH3 OH CCH2CH3 E1.815 CH CH2CN H CCH2CH3 E1.816 CH CH2CN CH3 CCH2CH3 E1.817 CH CH2CN CH2CH3 CCH2CH3 E1.818 CH CH2CN F CCH2CH3 E1.819 CH CH2CN Cl CCH2CH3 E1.820 CH CH2CN Br CCH2CH3 E1.821 CH CH2CN CN CCH2CH3 E1.822 CH CH2CN OCH3 CCH2CH3 E1.823 CH CH2CN OCH2CH3 CCH2CH3 E1.824 CH CH2CN OCH2CH2OCH3 CCH2CH3 E1.825 CH CH2CN OH CCH2CH3 E1.826 CH H CCH2CH3 E1.827 CH CH3 CCH2CH3 E1.828 CH CH2CH3 CCH2CH3 E1.829 CH F CCH2CH3 E1.830 CH Cl CCH2CH3 E1.831 CH Br CCH2CH3 E1.832 CH CN CCH2CH3 E1.833 CH OCH3 CCH2CH3 E1.834 CH OCH2CH3 CCH2CH3 E1.835 CH OCH2CH2OCH3 CCH2CH3 E1.836 CH OH CCH2CH3 E1.837 CH NHAc H CCH2CH3 E1.838 CH NHAc CH3 CCH2CH3 E1.839 CH NHAc CH2CH3 CCH2CH3 E1.840 CH NHAc F CCH2CH3 E1.841 CH NHAc Cl CCH2CH3 E1.842 CH NHAc Br CCH2CH3 E1.843 CH NHAc CN CCH2CH3 Compound A3b R2b R4 A3a E1.844 CH NHAc OCH3 CCH2CH3 E1.845 CH NHAc OCH2CH3 CCH2CH3 E1.846 CH NHAc OCH2CH2OCH3 CCH2CH3 E1.847 CH NHAc OH CCH2CH3 E1.848 N H H CCH2CH3 E1.849 N H CH3 CCH2CH3 E1.850 N H CH2CH3 CCH2CH3 E1.851 N H F CCH2CH3 E1.852 N H Cl CCH2CH3 E1.853 N H Br CCH2CH3 E1.854 N H CN CCH2CH3 E1.855 N H OCH3 CCH2CH3 E1.856 N H OCH2CH3 CCH2CH3 E1.857 N H OCH2CH2OCH3 CCH2CH3 E1.858 N H OH CCH2CH3 E1.859 N CH3 H CCH2CH3 E1.860 N CH3 CH3 CCH2CH3 E1.861 N CH3 CH2CH3 CCH2CH3 E1.862 N CH3 F CCH2CH3 E1.863 N CH3 Cl CCH2CH3 E1.864 N CH3 Br CCH2CH3 E1.865 N CH3 CN CCH2CH3 E1.866 N CH3 OCH3 CCH2CH3 E1.867 N CH3 OCH2CH3 CCH2CH3 E1.868 N CH3 OCH2CH2OCH3 CCH2CH3 E1.869 N CH3 OH CCH2CH3 E1.870 N CH2CH3 H CCH2CH3 E1.871 N CH2CH3 CH3 CCH2CH3 E1.872 N CH2CH3 CH2CH3 CCH2CH3 E1.873 N CH2CH3 F CCH2CH3 E1.874 N CH2CH3 Cl CCH2CH3 E1.875 N CH2CH3 Br CCH2CH3 E1.876 N CH2CH3 CN CCH2CH3 E1.877 N CH2CH3 OCH3 CCH2CH3 E1.878 N CH2CH3 OCH2CH3 CCH2CH3 E1.879 N CH2CH3 OCH2CH2OCH3 CCH2CH3 E1.880 N CH2CH3 OH CCH2CH3 E1.881 N CH2OCH3 H CCH2CH3 E1.882 N CH2OCH3 CH3 CCH2CH3 E1.883 N CH2OCH3 CH2CH3 CCH2CH3 E1.884 N CH2OCH3 F CCH2CH3 E1.885 N CH2OCH3 Cl CCH2CH3 E1.886 N CH2OCH3 Br CCH2CH3 E1.887 N CH2OCH3 CN CCH2CH3 E1.888 N CH2OCH3 OCH3 CCH2CH3 Compound A3b R2b R4 A3a E1.889 N CH2OCH3 OCH2CH3 CCH2CH3 E1.890 N CH2OCH3 OCH2CH2OCH3 CCH2CH3 E1.891 N CH2OCH3 OH CCH2CH3 E1.892 N CH2CN H CCH2CH3 E1.893 N CH2CN CH3 CCH2CH3 E1.894 N CH2CN CH2CH3 CCH2CH3 E1.895 N CH2CN F CCH2CH3 E1.896 N CH2CN Cl CCH2CH3 E1.897 N CH2CN Br CCH2CH3 E1.898 N CH2CN CN CCH2CH3 E1.899 N CH2CN OCH3 CCH2CH3 E1.900 N CH2CN OCH2CH3 CCH2CH3 E1.901 N CH2CN OCH2CH2OCH3 CCH2CH3 E1.902 N CH2CN OH CCH2CH3 E1.903 N H CCH2CH3 E1.904 N CH3 CCH2CH3 E1.905 N CH2CH3 CCH2CH3 E1.906 N F CCH2CH3 E1.907 N Cl CCH2CH3 E1.908 N Br CCH2CH3 E1.909 N CN CCH2CH3 E1.910 N OCH3 CCH2CH3 E1.911 N OCH2CH3 CCH2CH3 E1.912 N OCH2CH2OCH3 CCH2CH3 E1.913 N OH CCH2CH3 E1.914 N NHAc H CCH2CH3 E1.915 N NHAc CH3 CCH2CH3 E1.916 N NHAc CH2CH3 CCH2CH3 E1.917 N NHAc F CCH2CH3 E1.918 N NHAc Cl CCH2CH3 E1.919 N NHAc Br CCH2CH3 E1.920 N NHAc CN CCH2CH3 E1.921 N NHAc OCH3 CCH2CH3 E1.922 N NHAc OCH2CH3 CCH2CH3 E1.923 N NHAc OCH2CH2OCH3 CCH2CH3 E1.924 N NHAc OH CCH2CH3 E1.925 CH H H CCN E1.926 CH H CH3 CCN E1.927 CH H CH2CH3 CCN Compound A3b R2b R4 A3a E1.928 CH H F CCN E1.929 CH H Cl CCN E1.930 CH H Br CCN E1.931 CH H CN CCN E1.932 CH H OCH3 CCN E1.933 CH H OCH2CH3 CCN E1.934 CH H OCH2CH2OCH3 CCN E1.935 CH H OH CCN E1.936 CH CH3 H CCN E1.937 CH CH3 CH3 CCN E1.938 CH CH3 CH2CH3 CCN E1.939 CH CH3 F CCN E1.940 CH CH3 Cl CCN E1.941 CH CH3 Br CCN E1.942 CH CH3 CN CCN E1.943 CH CH3 OCH3 CCN E1.944 CH CH3 OCH2CH3 CCN E1.945 CH CH3 OCH2CH2OCH3 CCN E1.946 CH CH3 OH CCN E1.947 CH CH2CH3 H CCN E1.948 CH CH2CH3 CH3 CCN E1.949 CH CH2CH3 CH2CH3 CCN E1.950 CH CH2CH3 F CCN E1.951 CH CH2CH3 Cl CCN E1.952 CH CH2CH3 Br CCN E1.953 CH CH2CH3 CN CCN E1.954 CH CH2CH3 OCH3 CCN E1.955 CH CH2CH3 OCH2CH3 CCN E1.956 CH CH2CH3 OCH2CH2OCH3 CCN E1.957 CH CH2CH3 OH CCN E1.958 CH CH2OCH3 H CCN E1.959 CH CH2OCH3 CH3 CCN E1.960 CH CH2OCH3 CH2CH3 CCN E1.961 CH CH2OCH3 F CCN E1.962 CH CH2OCH3 Cl CCN E1.963 CH CH2OCH3 Br CCN E1.964 CH CH2OCH3 CN CCN E1.965 CH CH2OCH3 OCH3 CCN E1.966 CH CH2OCH3 OCH2CH3 CCN E1.967 CH CH2OCH3 OCH2CH2OCH3 CCN E1.968 CH CH2OCH3 OH CCN E1.969 CH CH2CN H CCN E1.970 CH CH2CN CH3 CCN E1.971 CH CH2CN CH2CH3 CCN E1.972 CH CH2CN F CCN Compound A3b R2b R4 A3a E1.973 CH CH2CN Cl CCN E1.974 CH CH2CN Br CCN E1.975 CH CH2CN CN CCN E1.976 CH CH2CN OCH3 CCN E1.977 CH CH2CN OCH2CH3 CCN E1.978 CH CH2CN OCH2CH2OCH3 CCN E1.979 CH CH2CN OH CCN E1.980 CH H CCN E1.981 CH CH3 CCN E1.982 CH CH2CH3 CCN E1.983 CH F CCN E1.984 CH Cl CCN E1.985 CH Br CCN E1.986 CH CN CCN E1.987 CH OCH3 CCN E1.988 CH OCH2CH3 CCN E1.989 CH OCH2CH2OCH3 CCN E1.990 CH OH CCN E1.991 CH NHAc H CCN E1.992 CH NHAc CH3 CCN E1.993 CH NHAc CH2CH3 CCN E1.994 CH NHAc F CCN E1.995 CH NHAc Cl CCN E1.996 CH NHAc Br CCN E1.997 CH NHAc CN CCN E1.998 CH NHAc OCH3 CCN E1.999 CH NHAc OCH2CH3 CCN E1.1000 CH NHAc OCH2CH2OCH3 CCN E1.1001 CH NHAc OH CCN E1.1002 N H H CCN E1.1003 N H CH3 CCN E1.1004 N H CH2CH3 CCN E1.1005 N H F CCN E1.1006 N H Cl CCN E1.1007 N H Br CCN E1.1008 N H CN CCN E1.1009 N H OCH3 CCN E1.1010 N H OCH2CH3 CCN E1.1011 N H OCH2CH2OCH3 CCN Compound A3b R2b R4 A3a E1.1012 N H OH CCN E1.1013 N CH3 H CCN E1.1014 N CH3 CH3 CCN E1.1015 N CH3 CH2CH3 CCN E1.1016 N CH3 F CCN E1.1017 N CH3 Cl CCN E1.1018 N CH3 Br CCN E1.1019 N CH3 CN CCN E1.1020 N CH3 OCH3 CCN E1.1021 N CH3 OCH2CH3 CCN E1.1022 N CH3 OCH2CH2OCH3 CCN E1.1023 N CH3 OH CCN E1.1024 N CH2CH3 H CCN E1.1025 N CH2CH3 CH3 CCN E1.1026 N CH2CH3 CH2CH3 CCN E1.1027 N CH2CH3 F CCN E1.1028 N CH2CH3 Cl CCN E1.1029 N CH2CH3 Br CCN E1.1030 N CH2CH3 CN CCN E1.1031 N CH2CH3 OCH3 CCN E1.1032 N CH2CH3 OCH2CH3 CCN E1.1033 N CH2CH3 OCH2CH2OCH3 CCN E1.1034 N CH2CH3 OH CCN E1.1035 N CH2OCH3 H CCN E1.1036 N CH2OCH3 CH3 CCN E1.1037 N CH2OCH3 CH2CH3 CCN E1.1038 N CH2OCH3 F CCN E1.1039 N CH2OCH3 Cl CCN E1.1040 N CH2OCH3 Br CCN E1.1041 N CH2OCH3 CN CCN E1.1042 N CH2OCH3 OCH3 CCN E1.1043 N CH2OCH3 OCH2CH3 CCN E1.1044 N CH2OCH3 OCH2CH2OCH3 CCN E1.1045 N CH2OCH3 OH CCN E1.1046 N CH2CN H CCN E1.1047 N CH2CN CH3 CCN E1.1048 N CH2CN CH2CH3 CCN E1.1049 N CH2CN F CCN E1.1050 N CH2CN Cl CCN E1.1051 N CH2CN Br CCN E1.1052 N CH2CN CN CCN E1.1053 N CH2CN OCH3 CCN E1.1054 N CH2CN OCH2CH3 CCN E1.1055 N CH2CN OCH2CH2OCH3 CCN E1.1056 N CH2CN OH CCN Compound A3b R2b R4 A3a E1.1057 N H CCN E1.1058 N CH3 CCN E1.1059 N CH2CH3 CCN E1.1060 N F CCN E1.1061 N Cl CCN E1.1062 N Br CCN E1.1063 N CN CCN E1.1064 N OCH3 CCN E1.1065 N OCH2CH3 CCN E1.1066 N OCH2CH2OCH3 CCN E1.1067 N OH CCN E1.1068 N NHAc H CCN E1.1069 N NHAc CH3 CCN E1.1070 N NHAc CH2CH3 CCN E1.1071 N NHAc F CCN E1.1072 N NHAc Cl CCN E1.1073 N NHAc Br CCN E1.1074 N NHAc CN CCN E1.1075 N NHAc OCH3 CCN E1.1076 N NHAc OCH2CH3 CCN E1.1077 N NHAc OCH2CH2OCH3 CCN E1.1078 N NHAc OH CCN Table 1.2 provides compounds E2.1 to E2.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 * W is CH3, ring W # is , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.3 provides compounds E3.1 to E3.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 * * represents the point of attachment to the
Figure imgf000042_0001
, the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.4 provides compounds E4.1 to E4.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 * * represents the point of attachment to the
Figure imgf000043_0001
, the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.5 provides compounds E5.1 to E5.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 * * represents the point of attachment to the
Figure imgf000043_0002
, the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.6 provides compounds E6.1 to E6.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 , wherein * represents the point of attachment to the
Figure imgf000043_0003
, # represents the point of attachment to the ring formed by the A3 groups,and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.7 provides compounds E7.1 to E7.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 , wherein * represents the point of attachment to the
Figure imgf000043_0004
, represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.8 provides compounds E8.1 to E8.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 * * represents the point of attachment to the
Figure imgf000043_0005
, the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.9 provides compounds E9.1 to E9.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 * , wherein * represents the point of attachment to the
Figure imgf000043_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.10 provides compounds E10.1 to E10.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000044_0001
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.11 provides compounds E11.1 to E11.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3,
Figure imgf000044_0002
, the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.12 provides compounds E12.1 to E12.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000044_0003
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.13 provides compounds E13.1 to E13.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000044_0004
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.14 provides compounds E14.1 to E14.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000044_0005
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.15 provides compounds 1.15.1 to E15.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000044_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.16 provides compounds E16.1 to E16.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000045_0001
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.17 provides compounds E17.1 to E17.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3,
Figure imgf000045_0002
, the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.18 provides compounds E18.1 to E18.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000045_0003
, the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.19 provides compounds E19.1 to E19.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000045_0004
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.20 provides compounds E20.1 to E20.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000045_0005
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.21 provides compounds E21.1 to E21.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000045_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.22 provides compounds E22.1 to E22.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000046_0001
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.23 provides compounds E23.1 to E23.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000046_0002
group , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.24 provides compounds E24.1 to E24.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000046_0003
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.25 provides compounds E25.1 to E25.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000046_0004
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.26 provides compounds E26.1 to E26.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000046_0005
group , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.27 provides compounds E27.1 to E27.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000046_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z.Table 1.28 provides compounds E28.1 to *
Figure imgf000047_0005
1), and # represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.29 provides compounds E29.1 to E29.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000047_0001
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.30 provides compounds E30.1 to 1.30.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000047_0002
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.31 provides compounds E31.1 to E31.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000047_0003
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.32 provides compounds E32.1 to E32.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000047_0004
imidazopyridine , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.33 provides compounds E33.1 to E33.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, , wherein * represents the point of attachment to the
Figure imgf000048_0001
, the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.34 provides compounds E34.1 to E34.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, , wherein * represents the point of attachment to the
Figure imgf000048_0002
, the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.35 provides compounds E35.1 to E35.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000048_0003
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.36 provides compounds E36.1 to E36.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000048_0004
imidazopyridine , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.37 provides compounds E37.1 to E37.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000048_0005
imidazopyridine , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.38 provides compounds E38.1 to E38.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000048_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.39 provides compounds E39.1 to E39.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000049_0001
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.40 provides compounds E40.1 to E40.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000049_0002
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.41 provides compounds E41.1 to E41.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000049_0003
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.42 provides compounds E42.1 to E42.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000049_0004
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.43 provides compounds E43.1 to E43.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000049_0005
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.44 provides compounds E44.1 to E44.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3,
Figure imgf000049_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.45 provides compounds E45.1 to E45.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000050_0001
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.46 provides compounds E46.1 to E46.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000050_0002
imidazopyridine group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.47 provides compounds E47.1 to E47.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000050_0003
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.48 provides compounds E48.1 to E48.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000050_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.49 provides compounds E49.1 to E49.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000050_0005
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.50 provides compounds E50.1 to E50.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000050_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.51 provides compounds E51.1 to E51.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000051_0001
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.52 provides compounds E52.1 to E52.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000051_0002
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.53 provides compounds E53.1 to E53.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000051_0003
group , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.54 provides compounds E54.1 to E54.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000051_0004
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.55 provides compounds E55.1 to E55.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000051_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.56 provides compounds E56.1 to E56.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is , , wherein * represents the point of attachment to the
Figure imgf000051_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.57 provides compounds E57.1 to E57.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000052_0001
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.58 provides compounds E58.1 to E58.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000052_0002
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.59 provides compounds E59.1 to E59.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000052_0003
, represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.60 provides compounds E60.1 to E60.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, , wherein * represents the point of attachment to the
Figure imgf000052_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.61 provides compounds E61.1 to E61.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, , wherein * represents the point of attachment to the
Figure imgf000052_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.62 provides compounds E62.1 to E62.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000053_0001
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.63 provides compounds E63.1 to E63.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000053_0002
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.64 provides compounds E64.1 to E64.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000053_0003
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.65 provides compounds E65.1 to E65.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000053_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.66 provides compounds E66.1 to E66.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000053_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.67 provides compounds E67.1 to E67.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000053_0006
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.68 provides compounds E68.1 to E68.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, , wherein * represents the point of attachment to the
Figure imgf000054_0001
, represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.69 provides compounds E69.1 to E69.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000054_0002
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.70 provides compounds E70.1 to E70.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000054_0003
, represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.71 provides compounds E71.1 to E71.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000054_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.72 provides compounds E72.1 to E72.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, , wherein * represents the point of attachment to the
Figure imgf000054_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.73 provides compounds E73.1 to E73.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000054_0006
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.74 provides compounds E74.1 to E74.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * # , wherein * represents the point of attachment to the
Figure imgf000055_0001
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.75 provides compounds E75.1 to E75.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000055_0002
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.76 provides compounds E76.1 to E76.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000055_0003
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.77 provides compounds E77.1 to E77.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000055_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.78 provides compounds E78.1 to E78.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000055_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.79 provides compounds E79.1 to E79.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * , wherein * represents the point of attachment to the
Figure imgf000055_0006
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.80 provides compounds E80.1 to E80.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000056_0001
, the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.81 provides compounds E81.1 to E81.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000056_0002
group , represents the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.82 provides compounds E82.1 to E82.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000056_0003
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.83 provides compounds E83.1 to E83.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000056_0004
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.84 provides compounds E84.1 to E84.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000056_0005
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.85 provides compounds E85.1 to E85.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000056_0006
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.86 provides compounds E86.1 to E86.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000057_0001
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.87 provides compounds E87.1 to E87.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000057_0002
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.88 provides compounds E88.1 to E88.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000057_0003
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.89 provides compounds E89.1 to E89.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000057_0004
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.90 provides compounds E90.1 to E90.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3,
Figure imgf000057_0005
, the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.91 provides compounds E91.1 to E91.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000057_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.92 provides compounds E92.1 to E92.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000058_0001
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.93 provides compounds E93.1 to E93.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000058_0002
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.94 provides compounds E94.1 to E94.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000058_0003
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.95 provides compounds E95.1 to E95.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000058_0004
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.96 provides compounds E96.1 to E96.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000058_0005
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.97 provides compounds E97.1 to E97.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000058_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.98 provides compounds E98.1 to E98.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, * R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000059_0001
group , represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.99 provides compounds E99.1 to E99.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000059_0002
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.100 provides compounds E100.1 to E100.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000059_0003
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.101 provides compounds E101.1 to E101.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000059_0004
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.102 provides compounds E102.1 to E102.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000059_0005
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.103 provides compounds E103.1 to E103.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000060_0001
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.104 provides compounds E104.1 to E104.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000060_0002
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.105 provides compounds E105.1 to E105.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000060_0003
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.106 provides compounds E106.1 to E106.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000060_0004
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.107 provides compounds E107.1 to E107.1078 of formula (I-1) wherein A is CH, R2a is H, R2c * is H, R6 is CH3, , wherein * represents the point of attachment to
Figure imgf000060_0005
the , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.108 provides compounds E108.1 to E108.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000060_0006
imidazopyridine , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.109 provides compounds E109.1 to E109.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to
Figure imgf000061_0001
the , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.110 provides compounds E110.1 to E110.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000061_0002
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.111 provides compounds E111.1 to E111.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000061_0003
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.112 provides compounds E112.1 to E112.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000061_0004
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.113 provides compounds E113.1 to E113.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000061_0005
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.114 provides compounds E114.1 to E114.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000061_0006
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.115 provides compounds E115.1 to E115.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, rin , wherein * represents the point of attachment to the
Figure imgf000062_0001
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.116 provides compounds E116.1 to E116.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000062_0002
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.117 provides compounds E117.1 to E117.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000062_0003
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.118 provides compounds E118.1 to E118.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000062_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.119 provides compounds E119.1 to E119.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000062_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.120 provides compounds E120.1 to E120.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000062_0006
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.121 provides compounds E121.1 to E121.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000063_0001
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.122 provides compounds E122.1 to E122.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000063_0002
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.123 provides compounds E123.1 to E123.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000063_0003
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.124 provides compounds E124.1 to E124.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * W H, R6 is OCH3, ring W # is , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.125 provides compounds E125.1 to E125.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000063_0004
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.126 provides compounds E126.1 to E126.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to
Figure imgf000063_0005
the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.127 provides compounds E127.1 to E127.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000064_0001
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.128 provides compounds E128.1 to E128.1078 of formula (I-1) wherein A is N, R2a is H, R2c is H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000064_0002
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.129 provides compounds E129.1 to E129.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to
Figure imgf000064_0003
the , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.130 provides compounds E130.1 to E130.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to
Figure imgf000064_0004
the group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.131 provides compounds E131.1 to E131.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to
Figure imgf000064_0005
the group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.132 provides compounds E132.1 to E132.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to the
Figure imgf000064_0006
imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.133 provides compounds E133.1 to E133.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is OCH3, , wherein * represents the point of attachment to
Figure imgf000065_0001
the group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.134 provides compounds E134.1 to E134.1078 of formula (I-1) wherein A is CH, R2a is H, R2c * is H, R6 is CH3, , wherein * represents the point of attachment to
Figure imgf000065_0002
the , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.135 provides compounds E135.1 to E135.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000065_0003
imidazopyridine , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.136 provides compounds E136.1 to E136.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is , , wherein * represents the point of attachment to the
Figure imgf000065_0004
imidazopyridine , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.137 provides compounds E137.1 to E137.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is , , wherein * represents the point of attachment to
Figure imgf000065_0005
the group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.138 provides compounds E138.1 to E138.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is , , wherein * represents the point of attachment to
Figure imgf000065_0006
the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.139 provides compounds E139.1 to E139.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000066_0001
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.140 provides compounds E140.1 to E140.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000066_0002
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.141 provides compounds E141.1 to E141.1078 of formula (I-1) wherein A is N, R2a is H, R2c is , wherein * represents the point of attachment to the
Figure imgf000066_0003
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.142 provides compounds E142.1 to E142.1078 of formula (I-1) wherein A is N, R2a is H, R2c is , wherein * represents the point of attachment to the
Figure imgf000066_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.143 provides compounds E143.1 to E143.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000066_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.144 provides compounds E144.1 to E144.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000067_0001
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.145 provides compounds E145.1 to E145.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000067_0002
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.146 provides compounds E146.1 to E146.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000067_0003
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.147 provides compounds E147.1 to E147.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000067_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.148 provides compounds E148.1 to E148.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000067_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.149 provides compounds E149.1 to E149.1078 of formula (I-1) wherein A is N, R2a is H, R2c is , wherein * represents the point of attachment to the
Figure imgf000067_0006
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.150 provides compounds E150.1 to E150.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000068_0001
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.151 provides compounds E151.1 to E151.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * W H, R6 is , ring W # is , wherein * represents the point of attachment to the imidazopyridine group in formula (I-1), and # represents the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.152 provides compounds E152.1 to E152.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000068_0002
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.153 provides compounds E153.1 to E153.1078 of formula (I-1) wherein A is N, R2a is H, R2c is , wherein * represents the point of attachment to the
Figure imgf000068_0003
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.154 provides compounds E154.1 to E154.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * , wherein * represents the point of attachment to the
Figure imgf000068_0004
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.155 provides compounds E155.1 to E155.1078 of formula (I-1) wherein A is N, R2a is H, R2c is , wherein * represents the point of attachment to the
Figure imgf000068_0005
, the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.156 provides compounds E156.1 to E156.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is , , wherein * represents the point of attachment to
Figure imgf000069_0001
the , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.157 provides compounds E157.1 to E157.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is , , wherein * represents the point of attachment to the
Figure imgf000069_0002
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.158 provides compounds E158.1 to E158.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is , , wherein * represents the point of attachment to
Figure imgf000069_0003
the group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.159 provides compounds E159.1 to E159.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is , , wherein * represents the point of attachment to the
Figure imgf000069_0004
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.160 provides compounds E160.1 to E160.1078 of formula (I-1) wherein A is N, R2a is H, R2c is * H, R6 is , , wherein * represents the point of attachment to the
Figure imgf000069_0005
imidazopyridine group , the point of attachment to the ring formed by the A3 groups, A3a, A3b, R2b, R4 are as defined in table Z. Table 1.161 provides compounds E161.1 to E161.1078 of formula (I-1) wherein A is CH, R2a is H, R2c * is H, R6 is CH3, , wherein * represents the point of attachment to
Figure imgf000069_0006
fthe , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Table 1.162 provides compounds E162.1 to E162.1078 of formula (I-1) wherein A is CH, R2a is H, R2c is H, R6 is CH3, , wherein * represents the point of attachment to the
Figure imgf000070_0001
imidazopyridine , the point of attachment to the ring formed by the A3 groups, and A3a, A3b, R2b, R4 are as defined in table Z. Compounds according to the invention may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile, improved physico-chemical properties, or increased biodegradability). Compounds according to the invention have particularly advantageous levels of biological activity for protecting plants against oomycetes such as Phytophthora, Plasmopara and Pythium. Compounds of formula (I) according to the invention can be made as shown in the following schemes 1 to 22, in which, unless otherwise stated, the definition of each variable is as defined in the present invention. Compounds of formula (I) can be prepared via Suzuki cross coupling of compounds of formula (II), wherein X is Cl, Br or I, and a compound of formula (III), wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate, chloro(2- dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. This transformation is depicted in Scheme 1.
Figure imgf000070_0002
Scheme 1 Compounds of formula (IIa), wherein A1 is a carbon atom in formula II, wherein X is Cl, Br or I, and wherein X is more preferably Cl, can be prepared by the reaction of a compound of formula (Va), wherein X is Cl, Br, I or a triflate group, and wherein X is more preferably Br, I or a triflate group, with a compounds of formula (IV) wherein X is Cl, Br or I, and wherein X is more preferably Cl, and wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. This transformation is depicted in Scheme 2.
Figure imgf000071_0001
Compounds of formula (Va), wherein X is Cl, Br or I, can be prepared by the reaction of a compound of formula (VIa) with a halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide, N- iodosuccinimide, bromine or iodine, and, optionally, a base such as lithium di-isopropylamine or butyl lithium, in a suitable solvent, such as DMF, acetonitrile, dichloromethane, tetrahydrofuran or acetic acid. Alternatively, compounds of formula (Va), wherein X is Cl, Br, I or a triflate group, can be prepared by the reaction of a compound of formula (VIIa) with triflic anhydride and, optionally, a base, such as triethylamine or pyridine, or a halogenating agent such as phosphorus oxychloride, phosphorus oxybromide, or by successive reaction with phosphorus oxychloride and sodium iodide. These transformations are performed neat or in a suitable solvent such as dichloromethane, toluene or xylene. These transformations are depicted in Scheme 3. Compounds of formula (VIa) and compounds of formula (VIIa) are either commercially available or the person skilled in the art would know that they can be synthesized by known methods. Some methods for the synthesis of such heteroaromatic can be found in the following publication: J.A. Joule and K. Mills (2010), Heterocyclic Chemistry, Fifth Edition, Wiley-Blackwell; V.J. Ram, A. Sethi, M. Nath, R. Pratap (2019) The Chemistry of Heterocycles Nomenclature and Chemistry of Three to Five Membered Heterocycles, 1st Edition, Elsevier; V.J. Ram, A. Sethi, M. Nath, R. Pratap (2019) The Chemistry of Heterocycles Chemistry of Six to Eight Membered N,O,S,P and Se Heterocycles, 1st Edition, Elsevier. Furthermore, the person skilled in the art would also recognize that compounds of formula (VIa) and compounds of formula (VIIa) could easily be obtained by either C-C cross-coupling, C-N cross-coupling or via direct C-H activation. A subset of the vast literature describing such transformations is referenced here: J.-Q. Chen, J.-H. Li, Z.-B. Dong, Adv. Synth Catal.2020, 362, 3311; F. Bellina, R. Rossi, Adv. Synth. Catal.2010, 1223; E. Kang, H. T. Kim, J.M. Joo, Org. Biomol. Chem.2020, 18, 6192; Q. Yang, Y. Zhao, D. Ma, Org. Process Res. Dev.2022, 26, 1690; H. Kaddouri, V. Vicente, A. Ouali, F. Ouazzani, M. Taillefer, Angew. Chem. Int. Ed. 2009, 48, 333; J. J. Li and G. W. Gribble (2007) Palladium in Heterocyclic Chemistry, Second Edition, Elsevier; A. de Meijere, S. Bräse, M. Oestreich (2014) Metal- Catalyzed Cross-Coupling Reactions and More, Volume 1 to 3, Wiley-VCH. Compounds of formula (IV) wherein X is Cl, Br or I, and wherein X is more preferably Cl, and wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl can be prepared by the reaction of a compound of formula (VIII) with a halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide in a suitable solvent, such as DMF, acetonitrile, dichloromethane or tetrahydrofuran. This transformation is depicted in Scheme 4.
Figure imgf000072_0001
(VIII) (IV) Scheme 4 Compounds of formula (VIII) wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl can be prepared by the reaction of a compound of formula (IX), wherein X is Cl, Br or I, with a compound of formula (X) wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, such as bis(pinacolato)diborane, bis(neopentyl glycolato)diboron or diboronic acid, a catalyst, such as dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct or dichlorobis(tricyclohexylphosphine)palladium and, optionally, a base, such as potassium acetate, in a suitable solvent, such as DMF, acetonitrile, toluene, dioxane or tetrahydrofuran. Alternatively compounds of formula (VIII) wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl can be prepared by the reaction of a compound of formula (IX), wherein X is Cl, Br or I, with a compounds of formula (XI) wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, such as trimethyl borate, triisopropyl borate, isopropoxy 4,4,5,5-tetramethyl-1,3,2- dioxaborolane, or 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, and a metal halogen exchange reagent, such as butyl lithium or ethylmagnesium bromide, in a suitable solvent, such as tetrahydrofuran, diethyl ether or dioxane. These transformations are depicted in Scheme 5.
Figure imgf000073_0001
Compounds of formula (IX) are commercially available or, alternatively, can be prepared by the reaction of a compound of formula (XII), wherein X is Cl, Br or I, and a compound of formula (XIII), wherein X is Cl, Br or I, or its corresponding acetal of formula (XIV), wherein X is Cl, Br or I and either R10 is independently from each other C1-C6 alkyl or wherein two R10 together can form a C3-C8 cycloalkyl, in a solvent, such as water, ethanol, acetone or acetonitrile. In some instance, the outcome of the reaction can be improved by using a base, such as sodium bicarbonate or potassium carbonate, or by using an acid, such as p-toluenesulfonic acid or hydrogen bromide. This transformation is depicted in scheme 6. Compounds of formula (XII), wherein X is Cl, Br or I, are prepared by known methods or are commercially available. Alternatively, compounds of formula (II), wherein X is Cl, Br or I, and wherein X is more preferably Cl, can be prepared by the reaction of a compound of formula (XV), with a halogenating agent such as N- chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide in a suitable solvent, such as DMF, acetonitrile, dichloromethane or tetrahydrofuran. This transformation is depicted in Scheme 7
Figure imgf000074_0001
Compounds of formula (XVa) wherein A1 is a carbon atom in formula (XV), can be prepared by the reaction of a compound of formula (Va), wherein X is Cl, Br, I or a triflate group, with a compounds of formula (VIII), wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. This transformation is depicted in Scheme 8. 2b
Figure imgf000075_0001
Alternatively compounds of formula (Ia) wherein A1 is a carbon atom in formula (I), herein depicted as compound (Ia) can be prepared via Suzuki cross coupling of compounds of formula (XVI), wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, and a compound of formula (Va), wherein X is Cl, Br, I or a triflate group, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. This transformation is depicted in Scheme 9.
Figure imgf000075_0002
Compounds of formula (XVI) wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl can be prepared by the reaction of a compound of formula (XVII), wherein X is Cl, Br or I, with a compound of formula (X) wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, such as bis(pinacolato)diborane, bis(neopentyl glycolato)diboron or diboronic acid, a catalyst, such as dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct or dichlorobis(tricyclohexylphosphine)palladium and, optionally, a base, such as potassium acetate, in a suitable solvent, such as DMF, acetonitrile, toluene, dioxane or tetrahydrofuran. This transformation is depicted in Scheme 10.
Figure imgf000076_0001
Compounds of formula (XVII), wherein X is Cl, Br or I, can be prepared via Suzuki cross coupling of compounds of formula (III), wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, and a compound of formula (XVIII), wherein either X independently is Cl, Br or I, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. It is well understood by the person skilled in the art that to obtain compounds of formula (XVII) the halogen X from the imidazole ring of the imidazopyridine bicyclic system should be equally or more reactive than the halogen X from the pyridine ring of the imidazopyridine bicyclic system. The person skilled in the art would recognize that halogen reactivity increases from chloro to bromo to iodo. This transformation is depicted in Scheme 11.
Figure imgf000076_0002
Compounds of formula (XVIII), wherein either X is independently Cl, Br or I, can be prepared by the reaction of a compound of formula (IX), wherein X is Cl, Br or I, with a halogenating agent such as N- chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide in a suitable solvent, such as DMF, acetonitrile, dichloromethane or tetrahydrofuran. This transformation is depicted in Scheme 12.
Figure imgf000077_0001
Alternatively, compounds of formula (IIa), wherein A1 is a carbon atom in formula (II) wherein X is Cl, Br or I, and wherein X is more preferably Cl, can be prepared by the reaction of a compound of formula (XVIII), wherein either X is independently from each other Cl, Br or I, with a compounds of formula (XIXa) wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. This transformation is depicted in Scheme 13.
Figure imgf000077_0002
Compounds of formula (IIb) wherein A2 is a carbon atom in formula (II), wherein either X is Cl, Br or I, and wherein X is more preferably Cl, can be prepared by the reaction of a compound of formula (XXb), wherein either X is independently from each other Cl, Br or I, with a compounds of formula (XXI) wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. This transformation is depicted in Scheme 14. Compounds or formula (XXI) are either commercially available or can be prepared by the person skilled in the art using very well described procedures. Compounds of formula (XXb), wherein either X is independently from each other Cl, Br or I, can be prepared by the reaction of a compound of formula (XXIIb), wherein X is Cl, Br or I, with a halogenating agent such as N-chlorosuccinimide, N-bromosuccinimide or N-iodosuccinimide in a suitable solvent, such as DMF, acetonitrile, dichloromethane or tetrahydrofuran. This transformation is depicted in Scheme 15.
Figure imgf000078_0001
Compounds of formula (XXIId), wherein A1 and A2 are carbon atoms in formula (XXII), and wherein X is Cl, Br or I, can be prepared via Suzuki cross coupling of compounds of formula (XXIIId), wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, and a compound of formula (XVIII), wherein either X independently is Cl, Br or I, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1- bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. It is well understood by the person skilled in the art that to obtain compounds of formula (XXIId) the halogen X from the pyridine ring of the imidazopyridine bicyclic system should be equally or more reactive than the halogen X from the imidazole ring of the imidazopyridine bicyclic system. The person skilled in the art would recognize that halogen reactivity increases from chloro to bromo to iodo. This transformation is depicted in Scheme 16.
Figure imgf000079_0001
Compounds or formula (XXIIId) are either commercially available or can be prepared by the person skilled in the art using very well described procedures. Compounds of formula (XVc), wherein A1 is a nitrogen atom in formula (XV), can be prepared by the reaction of a compound of formula (IX), wherein X is Cl, Br or I, with a compound of formula (XXIVc), wherein A1 is a nitrogen atom in formula (XXIV) in the presence of a base, such as Cs2CO3, K2CO3, K2HPO4 or NaOtBu, and a suitable palladium catalyst, and a suitable palladium catalyst, such as XPhos Pd G3, t-BuXPhos Pd G3, Me3tBuXPhos Pd G3, JohnPhos Pd G3, RuPhos Pd G3, BrettPhos Pd G3 or tBuBrettPhos Pd G3, in a suitable solvent, such as dimethylformamide, dimethylacetamide, dioxane, tetrahydrofuran or toluene. This transformation is depicted in Scheme 17.
Figure imgf000079_0002
Alternatively, compounds of formula (XVc), wherein A1 is a nitrogen atom in formula (XV), can be prepared by the reaction of a compound of formula (VIII), wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, with a compound of formula (XXIVc) in the presence of a base, such as triethylamine, diisopropylethylamine, pyridine, Cs2CO3, K2CO3, K2HPO4 or NaOtBu, and a suitable catalyst, such as copper(II) acetate, copper(II) carbonate, copper(II) hydroxide, copper oxide, copper(I) iodide or copper(I) bromide, in a suitable solvent, such as dimethylformamide, dimethylacetamide, dioxane, acetonitrile, tetrahydrofuran or toluene. In some instances, the outcome of the reaction can be improved by adding boric acid or molecular sieves to the reaction mixture. It is understood that these transformations are done under air as oxygen is needed as a terminal oxidant. In some cases, the copper species might be used in stochiometric amount. This transformation is depicted in Scheme 18.
Figure imgf000080_0001
The person skilled in the art would also recognize that the compounds of formula (I) can alternatively be prepared by the de novo construction of the ring W. Such synthetic routes have been used and are described in the experimental section of the present invention. It is understood by the person skilled in the art that the synthetic routes describing the access to those specific compounds can also be used to synthesize analogous compounds of formula (I) of this specific compound, wherein said compounds have identical ring W. These routes described in the experimental section should thus also be considered as general routes for accessing compounds of formula (I). The below compounds of formula (I-a) and (II-a) can be prepared following the synthetic route used in the example 30. The example 30 describes the preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrazol- 3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 76). This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is a pyrazole (compounds of formula (I- a)) as well as the synthesis of compounds of formula (II), wherein W is a pyrazole and X is Cl, Br or I (compounds of formula (II-a)). This methodology can be used in general terms to access analogous compounds of formula (I-a) and formula (II-a). (I-a) (II-a) The below compounds of formula (I-b) and (II-b) can be prepared following the synthetic route used in the example 29. The example 29 describes the preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 75). This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is a triazole (compounds of formula (I-b)) as well as the synthesis of compounds of formula (II), wherein W is a triazole and X is Cl, Br or I (compounds of formula (II-b)). This methodology can be used in general terms to access analogous compounds of formula (I-b) and formula (II-b).
Figure imgf000081_0001
The below compounds of formula (I-c) and (II-c) can be prepared following the synthetic route used in the examples 25, 27 and 28. The example 28 describes the preparation of methyl N-[5-[6-[2-(4-fluoro- 3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]80yridine-3-yl]-2-pyridyl]carbamate (compound 4), the example 27 describes the preparation of methyl N-[5-[6-[5-cyano-2-(4-fluorophenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]80yridine-3-yl]-2-pyridyl]carbamate (compound 74), and the example 25 describes the preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 33). These synthetic routes describe the de novo synthesis of a compound of formula (I), wherein ring W is a triazole (compounds of formula (I-c)) as well as the synthesis of compounds of formula (II), wherein W is a triazole and X is Cl, Br or I (compounds of formula (II-c)). These methodologies can be used in general terms to access analogous compounds of formula (I-c) and formula (II-c). The below compounds of formula (I-d) and (II-d) can be prepared following the synthetic route used in the example 9. The example 9 describes the preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy- phenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 10). This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is an oxadiazine (compounds of formula (I-d)) as well as the synthesis of compounds of formula (II), wherein W is an oxadiazine and X is Cl, Br or I (compounds of formula (II-d)). This methodology can be used in general terms to access analogous compounds of formula (I-d) and formula (II-d).
Figure imgf000082_0001
The below compounds of formula (I-e) and (II-e) can be prepared following the synthetic route used in the example 7. The example 7 describes the preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy- phenyl)-5-oxo-1,2,4-oxadiazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 32). This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is an oxadiazolone (compounds of formula (I-e)) as well as the synthesis of compounds of formula (II), wherein W is an oxadiazolone and X is Cl, Br or I (compounds of formula (II-e)). This methodology can be used in general terms to access analogous compounds of formula (I-e) and formula (II-e). The below compounds of formula (I-f) and (II-f) can be prepared following the synthetic route used in the example 38. The example 38 describes the preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy- phenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 9).This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is a triazole (compounds of formula (I-f)) as well as the synthesis of compounds of formula (II), wherein W is a triazole and X is Cl, Br or I (compounds of formula (II-f)). This methodology can be used in general terms to access analogous compounds of formula (I-f) and formula (II-f). 2b 2b
Figure imgf000083_0001
(I-f) (II-f) The below compounds of formula (I-g) and (II-g) can be prepared following the synthetic route used in the example 35. The example 35 describes the preparation of methyl N-[5-[6-[1-(4-fluoro-3-methoxy- phenyl)imidazol-2-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 8).This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is an imidazole (compounds of formula (I-g)) as well as the synthesis of compounds of formula (II), wherein W is an imidazole and X is Cl, Br or I (compounds of formula (II-g)). This methodology can be used in general terms to access analogous compounds of formula (I-g) and formula (II-g). 2b 2b
Figure imgf000084_0001
The below compounds of formula (I-h) and (II-h) can be prepared following the synthetic route used in the example 6. The example 6 describes the preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy- phenyl)-1-methyl-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 20).This synthetic route describes the de novo synthesis of a compound of formula (I), wherein ring W is a pyrazole (compounds of formula (I-h)) as well as the synthesis of compounds of formula (II), wherein W is a pyrazole and X is Cl, Br or I (compounds of formula (II-h)). This methodology can be used in general terms to access analogous compounds of formula (I-h) and formula (II-h).
Figure imgf000084_0002
In some instances, these de novo synthesis might require using compounds of formula (XVI), wherein X is Cl, Br or I, and R9 is hydrogen or C1-C6 alkyl, or the use of compound of formula (XVII), wherein R9 is hydrogen or C1-C6 alkyl. Compounds of formula (XVI), wherein X is Cl, Br or I and R9 is hydrogen or C1-C6 alkyl, are commercially available or, alternatively, can be prepared from the reaction of a compound of formula (XVII), wherein R9 is a hydrogen or C1-C6 alkyl, and a halogenating agent, such as N-chlorosuccinimide, N- bromosuccinimide, N-iodosuccinimide or bromine in a suitable solvent, such as dichloromethane, chloroform, tetrahydrofuran or acetonitrile. This transformation is depicted in scheme 19. Compounds of formula (XVII), wherein R9 is hydrogen or C1-C6 alkyl, are commercially available or, alternatively, can be prepared by the reaction of a compound of formula (IX), wherein X is Cl, Br or I, with carbon monoxide and an alcohol R9OH, wherein R9 is a C1-C6 alkyl, or water, in the presence of a catalyst, such as PdCl2dppf, and, optionally, a base such as triethylamine. This transformation is depicted in scheme 20.
Figure imgf000085_0001
Alternatively, compounds of formula (XVII), wherein R9 is hydrogen or C1-C6 alkyl, can be prepared by the reaction of a compound of formula (XXV), wherein R9 is hydrogen or C1-C6 alkyl, and a compound of formula (XIII), wherein X is Cl, Br or I, or its corresponding acetal of formula (XIV), wherein X is Cl, Br or I and either R10 is independently from each other C1-C6 alkyl or wherein two R10 together can form a C3-C8 cycloalkyl, in a solvent, such as water, ethanol, acetone or acetonitrile. In some instance, the outcome of the reaction can be improved by using a base, such as sodium bicarbonate or potassium carbonate, or by using an acid, such as p-toluenesulfonic acid or hydrogen bromide. Compounds of formula (XXV), wherein R9 is hydrogen or C1-C6 alkyl, are prepared by known methods or are commercially available. This transformation is depicted in Scheme 21. Alternatively, compounds of formula (I) can be obtained by acylation of compounds of formula (XXVI) using an acylation reagent of formula (XXVII), wherein X is Cl or Br, in the presence of a base such as triethylamine, pyridine or potassium carbonate. Compounds of formula (XXVI) can be prepared via Suzuki cross coupling of compounds of formula (II), wherein X is Cl, Br or I, and a compound of formula (XXVIII), wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, in the presence of a base, such as Cs2CO3, K2CO3 or NaOtBu, and a suitable palladium catalyst, such as tetrakistriphenylphosphinepalladium, palladium dichloride, [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), palladium acetate, chloro(2- dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) or bis(diphenylphosphine)palladium(II) chloride), in a suitable solvent, such as dimethylformamide, dioxane, tetrahydrofuran, ethanol or water. Compounds of formula (XXVII), wherein X is Cl or Br, and compounds of formula (XXVIII), wherein either R8 is independently from each other hydrogen, C1-C6 alkyl or wherein two R8 together can form a C3-C8 cycloalkyl, are commercially available or are prepared by known methods. This transformation is depicted in Scheme 22.
When the term “compound/compounds according to the invention” is used, then this refers to compounds according to the present invention. Alternatively, the compounds according to the present invention can be obtained by using standard synthesis techniques known to the person skilled in the art. Non-exhaustive examples include oxidation reactions, reduction reactions, hydrolysis reactions, coupling reactions, aromatic nucleophilic or electrophilic substitution reactions, nucleophilic substitution reactions, nucleophilic addition reactions, olefination reactions, oxime formation, alkylation and halogenation reactions. A compound according to the present invention can be converted in a manner known per se into another compound according to the present invention by replacing one or more substituents of the starting compound according to the present invention in the customary manner by (an)other substituent(s) according to the invention. Depending on the choice of the reaction conditions and starting materials which are suitable in each case, it is possible, for example, in one reaction step only to replace one substituent by another substituent according to the invention, or a plurality of substituents can be replaced by other substituents according to the invention in the same reaction step. Salts of the compounds according to the present invention can be prepared in a manner known per se. Thus, for example, acid addition salts of the compounds according to the present invention are obtained by treatment with a suitable acid or a suitable ion exchanger reagent and salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent. Salts of compounds the compounds according to the present invention can be converted in the customary manner into the free compounds, acid addition salts, for example, by treatment with a suitable basic compound or with a suitable ion exchanger reagent and salts with bases, for example, by treatment with a suitable acid or with a suitable ion exchanger reagent. Salts of the compounds according to the present invention can be converted in a manner known per se into other salts of the compounds according to the present invention, acid addition salts, for example, into other acid addition salts, for example by treatment of a salt of inorganic acid such as hydrochloride with a suitable metal salt such as a sodium, barium or silver salt, of an acid, for example with silver acetate, in a suitable solvent in which an inorganic salt which forms, for example silver chloride, is insoluble and thus precipitates from the reaction mixture. Depending on the procedure or the reaction conditions, the compounds according to the present invention, which have salt-forming properties can be obtained in free form or in the form of salts. The compounds according to the present invention and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can be present in the form of one of the stereoisomers which are possible or as a mixture of these, for example in the form of pure stereoisomers, such as antipodes and/or diastereomers, or as stereoisomer mixtures, such as enantiomer mixtures, for example racemates, diastereomer mixtures or racemate mixtures, depending on the number, absolute and relative configuration of asymmetric carbon atoms which occur in the molecule and/or depending on the configuration of non-aromatic double bonds which occur in the molecule; the invention relates to the pure stereoisomers and also to all stereoisomer mixtures which are possible and is to be understood in each case in this sense hereinabove and hereinbelow, even when stereochemical details are not mentioned specifically in each case. Diastereomer mixtures or racemate mixtures of the compounds according to the present invention, in free form or in salt form, which can be obtained depending on which starting materials and procedures have been chosen can be separated in a known manner into the pure diasteromers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography. Enantiomer mixtures, such as racemates, which can be obtained in a similar manner can be resolved into the optical antipodes by known methods, for example by recrystallization from an optically active solvent, by chromatography on chiral adsorbents, for example high-performance liquid chromatography (HPLC) on acetyl celulose, with the aid of suitable microorganisms, by cleavage with specific, immobilized enzymes, via the formation of inclusion compounds, for example using chiral crown ethers, where only one enantiomer is complexed, or by conversion into diastereomeric salts, for example by reacting a basic end-product racemate with an optically active acid, such as a carboxylic acid, for example camphor, tartaric or malic acid, or sulfonic acid, for example camphorsulfonic acid, and separating the diastereomer mixture which can be obtained in this manner, for example by fractional crystallization based on their differing solubilities, to give the diastereomers, from which the desired enantiomer can be set free by the action of suitable agents, for example basic agents. Pure diastereomers or enantiomers can be obtained according to the invention not only by separating suitable stereoisomer mixtures, but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the process according to the invention with starting materials of a suitable stereochemistry. N-oxides can be prepared by reacting a compound according to the present invention with a suitable oxidizing agent, for example the H2O2/urea adduct in the presence of an acid anhydride, e.g. trifluoroacetic anhydride. Such oxidations are known from the literature, for example from J. Med. Chem., 32 (12), 2561-73, 1989 or WO 00/15615. It is advantageous to isolate or synthesize in each case the biologically more effective stereoisomer, for example enantiomer or diastereomer, or stereoisomer mixture, for example enantiomer mixture or diastereomer mixture, if the individual components have a different biological activity. The compounds according to the present invention and, where appropriate, the tautomers thereof, in each case in free form or in salt form, can, if appropriate, also be obtained in the form of hydrates and/or include other solvents, for example those which may have been used for the crystallization of compounds which are present in solid form. The following Examples illustrate, but do not limit, the invention. The present invention also provides intermediates useful for the preparation of compounds according to the present invention. The below intermediates form a further aspect of the invention. A compound of formula (II) ; group (II), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2- 6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than four A3 are N, preferably no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, hydroxy, amino, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1- 6alkylaminocarbonyl and diC1-6alkylaminocarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; and wherein optionally two geminal R1 taken together with the carbon they are attached to form a carbonyl group; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, C1-6alkylcarbonyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1- 6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, and C1-6alkylcarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; and X is Cl, Br or I. A compound of formula (XV)
Figure imgf000091_0001
* wherein selected from:
Figure imgf000091_0002
Figure imgf000092_0001
; wherein * represents the point of attachment to the imidazopyridine group in formula (XV), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2- 6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than four A3 are N, preferably no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, hydroxy, amino, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1- 6alkylaminocarbonyl and diC1-6alkylaminocarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; and wherein optionally two geminal R1 taken together with the carbon they are attached to form a carbonyl group; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, C1-6alkylcarbonyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1- 6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, and C1-6alkylcarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN. A compound of formula (XXVI)
Figure imgf000093_0001
; wherein * represents the point of attachment to the imidazopyridine group in formula (XXVI), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2- 6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A is CH or N; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than four A3 are N, preferably no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, hydroxy, amino, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1- 6alkylaminocarbonyl and diC1-6alkylaminocarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; and wherein optionally two geminal R1 taken together with the carbon they are attached to form a carbonyl group; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, C1-6alkylcarbonyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1- 6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, and C1-6alkylcarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN. A compound of formula (XXII)
Figure imgf000094_0001
* wherein ring
Figure imgf000094_0002
I is selected from: , ; wherein * represents the point of attachment to the imidazopyridine group in formula (XXII) and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl and C2-6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl- C1-4alkyl, C2-6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A1 is a carbon or nitrogen atom; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and X is Cl, Br or I. A compound of formula (XVII) wherein A is CH or N;
Figure imgf000095_0001
R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; R6 is selected from C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1- 6alkylamino, diC1-6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino, wherein each of the C1- 6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1-6alkylamino, diC1- 6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino groups is optionally substituted with one to three substituents independently selected from halogen and CN; and X is Cl, Br or I. The compounds of formula (I) as defined in the present invention can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pathogens or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man. The novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and may be used for protecting numerous cultivated plants. The compounds of formula (I) as defined in the present invention can be used to inhibit or destroy the pathogens that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms. It is also possible to use compounds of formula (I) as defined in the present invention as fungicide. The term “fungicide” as used herein means a compound that controls, modifies, or prevents the growth of fungi. The term “fungicidally effective amount” means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection. It is also possible to use compounds of formula (I) as defined in the present invention as dressing agents for the treatment of plant propagation material, e.g., seed, such as fruits, tubers or grains, or plant cuttings (for example rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil. The propagation material can be treated with a composition comprising a compound of formula (I) as defined in the present invention before planting: seed, for example, can be dressed before being sown. The compounds of formula (I) as defined in the present invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated. Furthermore the compounds of formula (I) as defined in the present invention can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage, in hygiene management. In addition, the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint. Compounds of formula (I) as defined in the present invention and fungicidal compositions containing them may be used to control plant diseases caused by a broad spectrum of fungal plant pathogens. They are effective in controlling a broad spectrum of plant diseases, such as foliar pathogens of ornamental, turf, vegetable, field, cereal, and fruit crops. These fungi and fungal vectors of disease, as well as phytopathogenic bacteria and viruses, which may be controlled are for example: Absidia corymbifera, Alternaria spp, Aphanomyces spp, Ascochyta spp, Aspergillus spp. including A. flavus, A. fumigatus, A. nidulans, A. niger, A. terrus, Aureobasidium spp. including A. pullulans, Blastomyces dermatitidis, Blumeria graminis, Bremia lactucae, Botryosphaeria spp. including B. dothidea, B. obtusa, Botrytis spp. inclusing B. cinerea, Candida spp. including C. albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, C. tropicalis, Cephaloascus fragrans, Ceratocystis spp, Cercospora spp. including C. arachidicola, Cercosporidium personatum, Cladosporium spp, Claviceps purpurea, Coccidioides immitis, Cochliobolus spp, Colletotrichum spp. including C. musae, Cryptococcus neoformans, Diaporthe spp, Didymella spp, Drechslera spp, Elsinoe spp, Epidermophyton spp, Erwinia amylovora, Erysiphe spp. including E. cichoracearum, Eutypa lata, Fusarium spp. including F. culmorum, F. graminearum, F. langsethiae, F. moniliforme, F. oxysporum, F. proliferatum, F. subglutinans, F. solani, Gaeumannomyces graminis, Gibberella fujikuroi, Gloeodes pomigena, Gloeosporium musarum, Glomerella cingulate, Guignardia bidwellii, Gymnosporangium juniperi-virginianae, Helminthosporium spp, Hemileia spp, Histoplasma spp. including H. capsulatum, Laetisaria fuciformis, Leptographium lindbergi, Leveillula taurica, Lophodermium seditiosum, Microdochium nivale, Microsporum spp, Monilinia spp, Mucor spp, Mycosphaerella spp. including M. graminicola, M. pomi, Oncobasidium theobromaeon, Ophiostoma piceae, Paracoccidioides spp, Penicillium spp. including P. digitatum, P. italicum, Petriellidium spp, Peronosclerospora spp. Including P. maydis, P. philippinensis and P. sorghi, Peronospora spp, Phaeosphaeria nodorum, Phakopsora pachyrhizi, Phellinus igniarus, Phialophora spp, Phoma spp, Phomopsis viticola, Phytophthora spp. including P. infestans, Plasmopara spp. including P. halstedii, P. viticola, Pleospora spp., Podosphaera spp. including P. leucotricha, Polymyxa graminis, Polymyxa betae, Pseudocercosporella herpotrichoides, Pseudomonas spp, Pseudoperonospora spp. including P. cubensis, P. humuli, Pseudopeziza tracheiphila, Puccinia Spp. including P. hordei, P. recondita, P. striiformis, P. triticina, Pyrenopeziza spp, Pyrenophora spp, Pyricularia spp. including P. oryzae, Pythium spp. including P. ultimum, Ramularia spp, Rhizoctonia spp, Rhizomucor pusillus, Rhizopus arrhizus, Rhynchosporium spp, Scedosporium spp. including S. apiospermum and S. prolificans, Schizothyrium pomi, Sclerotinia spp, Sclerotium spp, Septoria spp, including S. nodorum, S. tritici, Sphaerotheca macularis, Sphaerotheca fusca (Sphaerotheca fuliginea), Sporothorix spp, Stagonospora nodorum, Stemphylium spp,. Stereum hirsutum, Thanatephorus cucumeris, Thielaviopsis basicola, Tilletia spp, Trichoderma spp. including T. harzianum, T. pseudokoningii, T. viride, Trichophyton spp, Typhula spp, Uncinula necator, Urocystis spp, Ustilago spp, Venturia spp. including V. inaequalis, Verticillium spp, and Xanthomonas spp. In particular, compounds of formula (I) as defined in the present invention and fungicidal compositions containing them may be used to control plant diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete and/or Deuteromycete, Blasocladiomycete, Chrytidiomycete, Glomeromycete and/or Mucoromycete classes. More particularly, the compounds of formula (I) as defined in the present invention may be used to conrol oomycetes. These pathogens may include: Oomycetes, including Phytophthora diseases such as those caused by Phytophthora capsici, Phytophthora infestans, Phytophthora sojae, Phytophthora fragariae, Phytophthora nicotianae, Phytophthora cinnamomi, Phytophthora citricola, Phytophthora citrophthora and Phytophthora erythroseptica; Pythium diseases such as those caused by Pythium aphanidermatum, Pythium arrhenomanes, Pythium graminicola, Pythium irregulare, Pythium sylvaticum and Pythium ultimum; diseases caused by Peronosporales such as Peronospora destructor, Peronospora parasitica, Plasmopara viticola, Plasmopara halstedii, Pseudoperonospora cubensis, Albugo candida, Sclerophthora macrospora and Bremia lactucae; and others such as Aphanomyces cochlioides, Labyrinthula zosterae, Peronosclerospora sorghi and Sclerospora graminicola. Ascomycetes, including blotch, spot, blast or blight diseases and/or rots for example those caused by Pleosporales such as Stemphylium solani, Stagonospora tainanensis, Spilocaea oleaginea, Setosphaeria turcica, Pyrenochaeta lycoperisici, Pleospora herbarum, Phoma destructiva, Phaeosphaeria herpotrichoides, Phaeocryptocus gaeumannii, Ophiosphaerella graminicola, Ophiobolus graminis, Leptosphaeria maculans, Hendersonia creberrima, Helminthosporium triticirepentis, Setosphaeria turcica, Drechslera glycines, Didymella bryoniae, Cycloconium oleagineum, Corynespora cassiicola, Cochliobolus sativus, Bipolaris cactivora, Venturia inaequalis, Pyrenophora teres, Pyrenophora tritici-repentis, Alternaria alternata, Alternaria brassicicola, Alternaria solani and Alternaria tomatophila, Capnodiales such as Septoria tritici, Septoria nodorum, Septoria glycines, Cercospora arachidicola, Cercospora sojina, Cercospora zeae-maydis, Cercosporella capsellae and Cercosporella herpotrichoides, Cladosporium carpophilum, Cladosporium effusum, Passalora fulva, Cladosporium oxysporum, Dothistroma septosporum, Isariopsis clavispora, Mycosphaerella fijiensis, Mycosphaerella graminicola, Mycovellosiella koepkeii, Phaeoisariopsis bataticola, Pseudocercospora vitis, Pseudocercosporella herpotrichoides, Ramularia beticola, Ramularia collo-cygni, Magnaporthales such as Gaeumannomyces graminis, Magnaporthe grisea, Pyricularia oryzae, Diaporthales such as Anisogramma anomala, Apiognomonia errabunda, Cytospora platani, Diaporthe phaseolorum, Discula destructiva, Gnomonia fructicola, Greeneria uvicola, Melanconium juglandinum, Phomopsis viticola, Sirococcus clavigignenti-juglandacearum, Tubakia dryina, Dicarpella spp., Valsa ceratosperma, and others such as Actinothyrium graminis, Ascochyta pisi, Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Asperisporium caricae, Blumeriella jaapii, Candida spp., Capnodium ramosum, Cephaloascus spp., Cephalosporium gramineum, Ceratocystis paradoxa, Chaetomium spp., Hymenoscyphus pseudoalbidus, Coccidioides spp., Cylindrosporium padi, Diplocarpon malae, Drepanopeziza campestris, Elsinoe ampelina, Epicoccum nigrum, Epidermophyton spp., Eutypa lata, Geotrichum candidum, Gibellina cerealis, Gloeocercospora sorghi, Gloeodes pomigena, Gloeosporium perennans; Gloeotinia temulenta, Griphospaeria corticola, Kabatiella lini, Leptographium microsporum, Leptosphaerulinia crassiasca, Lophodermium seditiosum, Marssonina graminicola, Microdochium nivale, Monilinia fructicola, Monographella albescens, Monosporascus cannonballus, Naemacyclus spp., Ophiostoma novo-ulmi, Paracoccidioides brasiliensis, Penicillium expansum, Pestalotia rhododendri, Petriellidium spp., Pezicula spp., Phialophora gregata, Phyllachora pomigena, Phymatotrichum omnivora, Physalospora abdita, Plectosporium tabacinum, Polyscytalum pustulans, Pseudopeziza medicaginis, Pyrenopeziza brassicae, Ramulispora sorghi, Rhabdocline pseudotsugae, Rhynchosporium secalis, Sacrocladium oryzae, Scedosporium spp., Schizothyrium pomi, Sclerotinia sclerotiorum, Sclerotinia minor; Sclerotium spp., Typhula ishikariensis, Seimatosporium mariae, Lepteutypa cupressi, Septocyta ruborum, Sphaceloma perseae, Sporonema phacidioides, Stigmina palmivora, Tapesia yallundae, Taphrina bullata, Thielviopsis basicola, Trichoseptoria fructigena, Zygophiala jamaicensis; powdery mildew diseases for example those caused by Erysiphales such as Blumeria graminis, Erysiphe polygoni, Uncinula necator, Sphaerotheca fuligena, Podosphaera leucotricha, Podospaera macularis Golovinomyces cichoracearum, Leveillula taurica, Microsphaera diffusa, Oidiopsis gossypii, Phyllactinia guttata and Oidium arachidis; molds for example those caused by Botryosphaeriales such as Dothiorella aromatica, Diplodia seriata, Guignardia bidwellii, Botrytis cinerea, Botryotinia allii, Botryotinia fabae, Fusicoccum amygdali, Lasiodiplodia theobromae, Macrophoma theicola, Macrophomina phaseolina, Phyllosticta cucurbitacearum; anthracnoses for example those caused by Glommerelales such as Colletotrichum gloeosporioides, Colletotrichum lagenarium, Colletotrichum gossypii, Glomerella cingulata, and Colletotrichum graminicola; and wilts or blights for example those caused by Hypocreales such as Acremonium strictum, Claviceps purpurea, Fusarium culmorum, Fusarium graminearum, Fusarium virguliforme, Fusarium oxysporum, Fusarium subglutinans, Fusarium oxysporum f.sp. cubense, Gerlachia nivale, Gibberella fujikuroi, Gibberella zeae, Gliocladium spp., Myrothecium verrucaria, Nectria ramulariae, Trichoderma viride, Trichothecium roseum, and Verticillium theobromae. Basidiomycetes, including smuts for example those caused by Ustilaginales such as Ustilaginoidea virens, Ustilago nuda, Ustilago tritici, Ustilago zeae, rusts for example those caused by Pucciniales such as Cerotelium fici, Chrysomyxa arctostaphyli, Coleosporium ipomoeae, Hemileia vastatrix, Puccinia arachidis, Puccinia cacabata, Puccinia graminis, Puccinia recondita, Puccinia sorghi, Puccinia hordei, Puccinia striiformis f.sp. Hordei, Puccinia striiformis f.sp. Secalis, Pucciniastrum coryli, or Uredinales such as Cronartium ribicola, Gymnosporangium juniperi-viginianae, Melampsora medusae, Phakopsora pachyrhizi, Phragmidium mucronatum, Physopella ampelosidis, Tranzschelia discolor and Uromyces viciae-fabae; and other rots and diseases such as those caused by Cryptococcus spp., Exobasidium vexans, Marasmiellus inoderma, Mycena spp., Sphacelotheca reiliana, Typhula ishikariensis, Urocystis agropyri, Itersonilia perplexans, Corticium invisum, Laetisaria fuciformis, Waitea circinata, Rhizoctonia solani, Thanetephorus cucurmeris, Entyloma dahliae, Entylomella microspora, Neovossia moliniae and Tilletia caries. Blastocladiomycetes, such as Physoderma maydis. Mucoromycetes, such as Choanephora cucurbitarum.; Mucor spp.; Rhizopus arrhizus. As well as diseases caused by other species and genera closely related to those listed above. In addition to their fungicidal activity, the compounds and compositions comprising compounds of formula (I) as defined in the present invention may also have activity against bacteria such as Erwinia amylovora, Erwinia caratovora, Xanthomonas campestris, Pseudomonas syringae, Strptomyces scabies and other related species as well as certain protozoa. Within the scope of the present invention, target crops and/or useful plants to be protected typically comprise perennial and annual crops, such as berry plants for example blackberries, blueberries, cranberries, raspberries and strawberries; cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass, centipede grass, fescue, ryegrass, St. Augustine grass and Zoysia grass; herbs such as basil, borage, chives, coriander, lavender, lovage, mint, oregano, parsley, rosemary, sage and thyme; legumes for example beans, lentils, peas and soya beans; nuts for example almond, cashew, ground nut, hazelnut, peanut, pecan, pistachio and walnut; palms for example oil palm; ornamentals for example flowers, shrubs and trees; other trees, for example cacao, coconut, olive and rubber; vegetables for example asparagus, aubergine, broccoli, cabbage, carrot, cucumber, garlic, lettuce, marrow, melon, okra, onion, pepper, potato, pumpkin, rhubarb, spinach and tomato; and vines for example grapes. The useful plants and / or target crops in accordance with the invention include conventional as well as genetically enhanced or engineered varieties such as, for example, insect resistant (e.g. Bt. and VIP varieties) as well as disease resistant, herbicide tolerant (e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®) and nematode tolerant varieties. By way of example, suitable genetically enhanced or engineered crop varieties include the Stoneville 5599BR cotton and Stoneville 4892BR cotton varieties. The term "useful plants" and/or “target crops” is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5- enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®. The term "useful plants" and/or “target crops” is to be understood as including those which naturally are or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include ^-endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins produced by scorpions, arachnids, wasps and fungi. An example of a crop that has been modified to express the Bacillus thuringiensis toxin is the Bt maize KnockOut ^ (Syngenta Seeds). An example of a crop comprising more than one gene that codes for insecticidal resistance and thus expresses more than one toxin is VipCot ^ (Syngenta Seeds). Crops or seed material thereof can also be resistant to multiple types of pests (so-called stacked transgenic events when created by genetic modification). For example, a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant, for example Herculex I ^ (Dow AgroSciences, Pioneer Hi-Bred International). The term "useful plants" and/or “target crops” is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0392225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0392225, WO 95/33818, and EP-A-0353191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. Toxins that can be expressed by transgenic plants include, for example, insecticidal proteins from Bacillus cereus or Bacillus popilliae; or insecticidal proteins from Bacillus thuringiensis, such as ^- endotoxins, e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1, Vip2, Vip3 or Vip3A; or insecticidal proteins of bacteria colonising nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins produced by animals, such as scorpion toxins, arachnid toxins, wasp toxins and other insect-specific neurotoxins; toxins produced by fungi, such as Streptomycetes toxins, plant lectins, such as pea lectins, barley lectins or snowdrop lectins; agglutinins; proteinase inhibitors, such as trypsin inhibitors, serine protease inhibitors, patatin, cystatin, papain inhibitors; ribosome- inactivating proteins (RIP), such as ricin, maize-RIP, abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion channel blockers, such as blockers of sodium or calcium channels, juvenile hormone esterase, diuretic hormone receptors, stilbene synthase, bibenzyl synthase, chitinases and glucanases. Further, in the context of the present invention there are to be understood by ^-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A, expressly also hybrid toxins, truncated toxins and modified toxins. Hybrid toxins are produced recombinantly by a new combination of different domains of those proteins (see, for example, WO 02/15701). Truncated toxins, for example a truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid replacements, preferably non-naturally present protease recognition sequences are inserted into the toxin, such as, for example, in the case of Cry3A055, a cathepsin-G- recognition sequence is inserted into a Cry3A toxin (see WO03/018810). More examples of such toxins or transgenic plants capable of synthesising such toxins are disclosed, for example, in EP-A-0374753, WO93/07278, WO95/34656, EP-A-0427529, EP-A-451878 and WO03/052073. The processes for the preparation of such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0367 474, EP-A-0401979 and WO 90/13651. The toxin contained in the transgenic plants imparts to the plants tolerance to harmful insects. Such insects can occur in any taxonomic group of insects, but are especially commonly found in the beetles (Coleoptera), two-winged insects (Diptera) and butterflies (Lepidoptera). Transgenic plants containing one or more genes that code for an insecticidal resistance and express one or more toxins are known and some of them are commercially available. Examples of such plants are: YieldGard ^ (maize variety that expresses a Cry1Ab toxin); YieldGard Rootworm ^ (maize variety that expresses a Cry3Bb1 toxin); YieldGard Plus ^ (maize variety that expresses a Cry1Ab and a Cry3Bb1 toxin); Starlink ^ (maize variety that expresses a Cry9C toxin); Herculex I ^ (maize variety that expresses a Cry1Fa2 toxin and the enzyme phosphinothricine N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B ^ (cotton variety that expresses a Cry1Ac toxin); Bollgard I ^ (cotton variety that expresses a Cry1Ac toxin); Bollgard II® (cotton variety that expresses a Cry1Ac and a Cry2Ab toxin); VipCot ^ (cotton variety that expresses a Vip3A and a Cry1Ab toxin); NewLeaf ^ (potato variety that expresses a Cry3A toxin); NatureGard ^, Agrisure® GT Advantage (GA21 glyphosate-tolerant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta ^. Further examples of such transgenic crops are: 1. Bt11 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31 790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a truncated Cry1Ab toxin. Bt11 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 2. Bt176 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31790 St. Sauveur, France, registration number C/FR/96/05/10. Genetically modified Zea mays which has been rendered resistant to attack by the European corn borer (Ostrinia nubilalis and Sesamia nonagrioides) by transgenic expression of a Cry1Ab toxin. Bt176 maize also transgenically expresses the enzyme PAT to achieve tolerance to the herbicide glufosinate ammonium. 3. MIR604 Maize from Syngenta Seeds SAS, Chemin de l'Hobit 27, F-31790 St. Sauveur, France, registration number C/FR/96/05/10. Maize which has been rendered insect-resistant by transgenic expression of a modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G- protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810. 4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9. MON 863 expresses a Cry3Bb1 toxin and has resistance to certain Coleoptera insects. 5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/ES/96/02. 6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, registration number C/NL/00/10. Genetically modified maize for the expression of the protein Cry1F for achieving resistance to certain Lepidoptera insects and of the PAT protein for achieving tolerance to the herbicide glufosinate ammonium. 7. NK603 × MON 810 Maize from Monsanto Europe S.A. 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C/GB/02/M3/03. Consists of conventionally bred hybrid maize varieties by crossing the genetically modified varieties NK603 and MON 810. NK603 × MON 810 Maize transgenically expresses the protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4, which imparts tolerance to the herbicide Roundup® (contains glyphosate), and also a Cry1Ab toxin obtained from Bacillus thuringiensis subsp. kurstaki which brings about tolerance to certain Lepidoptera, include the European corn borer. The term “locus” as used herein means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation. The term “plants” refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits. The term “plant propagation material” is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably “plant propagation material” is understood to denote seeds. Pesticidal agents referred to herein using their common name are known, for example, from "The Pesticide Manual", 19th Ed., British Crop Protection Council 2021. The compounds of formula (I) as defined in the present invention may be used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects. Suitable carriers and/or adjuvants, e.g. for agricultural use, can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890. Suspension concentrates are aqueous formulations in which finely divided solid particles of the active compound are suspended. Such formulations include anti-settling agents and dispersing agents and may further include a wetting agent to enhance activity as well an anti-foam and a crystal growth inhibitor. In use, these concentrates are diluted in water and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate. Wettable powders are in the form of finely divided particles which disperse readily in water or other liquid carriers. The particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller’s earth, kaolin clays, silicas and other readily wet organic or inorganic solids. Wettable powders normally contain from 5% to 95% of the active ingredient plus a small amount of wetting, dispersing or emulsifying agent. Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquid and may consist entirely of the active compound with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquid and normally applied as a spray to the area to be treated. The amount of active ingredient may range from 0.5% to 95% of the concentrate. Granular formulations include both extrudates and relatively coarse particles and are usually applied without dilution to the area in which treatment is required. Typical carriers for granular formulations include sand, fuller’s earth, attapulgite clay, bentonite clays, montmorillonite clay, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn cobs, ground peanut hulls, sugars, sodium chloride, sodium sulphate, sodium silicate, sodium borate, magnesia, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and other organic or inorganic materials which absorb or which can be coated with the active compound. Granular formulations normally contain 5% to 25% of active ingredients which may include surface-active agents such as heavy aromatic naphthas, kerosene and other petroleum fractions, or vegetable oils; and/or stickers such as dextrins, glue or synthetic resins. Dusts are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers. Microcapsules are typically droplets or granules of the active ingredient enclosed in an inert porous shell which allows escape of the enclosed material to the surroundings at controlled rates. Encapsulated droplets are typically 1 to 50 microns in diameter. The enclosed liquid typically constitutes 50 to 95% of the weight of the capsule and may include solvent in addition to the active compound. Encapsulated granules are generally porous granules with porous membranes sealing the granule pore openings, retaining the active species in liquid form inside the granule pores. Granules typically range from 1 millimetre to 1 centimetre and preferably 1 to 2 millimetres in diameter. Granules are formed by extrusion, agglomeration or prilling, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust and granular carbon. Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates. Other useful formulations for agrochemical applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents. Pressurised sprayers, wherein the active ingredient is dispersed in finely-divided form as a result of vaporisation of a low boiling dispersant solvent carrier, may also be used. Suitable agricultural adjuvants and/or carriers that are useful in formulating the compositions of the invention in the formulation types described above are well known to those skilled in the art. Liquid carriers that can be employed include, for example, water, toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetates, diacetonalcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkyl pyrrolidinone, ethyl acetate, 2-ethyl hexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol diacetate, glycerol monoacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropyl benzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy-propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octyl amine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc., ethylene glycol, propylene glycol, glycerine and N-methyl-2-pyrrolidinone. Water is generally the carrier of choice for the dilution of concentrates. Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay, fuller’s earth, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour and lignin. A broad range of surface-active agents are advantageously employed in both said liquid and solid compositions, especially those designed to be diluted with carrier before application. These agents, when used, normally comprise from 0.1% to 15% by weight of the formulation. They can be anionic, cationic, non-ionic or polymeric in character and can be employed as emulsifying agents, wetting agents, suspending agents or for other purposes. Typical surface active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulphate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-C.sub.18 ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol-C.sub. 16 ethoxylate; soaps, such as sodium stearate; alkylnaphthalenesulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono and dialkyl phosphate esters. Other adjuvants commonly utilized in agricultural compositions include crystallisation inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, anti- foaming agents, light-blocking agents, compatibilizing agents, antifoam agents, sequestering agents, neutralising agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, micronutrients, emollients, lubricants and sticking agents. In addition, further, other biocidally active ingredients or compositions may be combined with the compositions of the invention and used in the methods of the invention and applied simultaneously or sequentially with the compositions of the invention. When applied simultaneously, these further active ingredients may be formulated together with the compositions of the invention or mixed in, for example, the spray tank. These further biocidally active ingredients may be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides, plant growth regulators, and/or biologicals. The following combinations of a compound of formula I with another active substance in a weight ratio of 1:1 are preferred (where the abbreviation “TX” means “one compound selected from the compounds defined in the Tables 1.1 to 1.162 and Table A): an adjuvant selected from the group of substances consisting of petroleum oils (alternative name) (628) + TX; abamectin + TX, acequinocyl + TX, acetamiprid + TX, acetoprole + TX, acrinathrin + TX, acynonapyr + TX, afidopyropen + TX, afoxolaner + TX, alanycarb + TX, allethrin + TX, alpha-cypermethrin + TX, alphamethrin + TX, amidoflumet + TX, aminocarb + TX, azocyclotin + TX, bensultap + TX, benzoximate + TX, benzpyrimoxan + TX, betacyfluthrin + TX, beta-cypermethrin + TX, bifenazate + TX, bifenthrin + TX, binapacryl + TX, bioallethrin + TX, S-bioallethrin + TX, bioresmethrin + TX, bistrifluron + TX, broflanilide + TX, brofluthrinate + TX, bromophos-ethyl + TX, buprofezine + TX, butocarboxim + TX, cadusafos + TX, carbaryl + TX, carbosulfan + TX, cartap + TX, CAS number: 1632218-00-8 + TX, CAS number: 1808115-49-2 + TX, CAS number: 2032403-97-5 + TX, CAS number: 2044701-44-0 + TX, CAS number: 2128706-05-6 + TX, CAS number: 2095470-94-1 + TX, CAS number: 2377084-09-6 + TX, CAS number: 1445683-71-5 + TX, CAS number: 2408220-94-8 + TX, CAS number: 2408220-91-5 + TX, CAS number: 1365070-72-9 + TX, CAS number: 2171099-09-3 + TX, CAS number: 2396747-83-2 + TX, CAS number: 2133042-31-4 + TX, CAS number: 2133042-44-9 + TX, CAS number: 1445684-82-1 + TX, CAS number: 1445684-82-1 + TX, CAS number: 1922957-45-6 + TX, CAS number: 1922957-46- 7 + TX, CAS number: 1922957-47-8 + TX, CAS number: 1922957-48-9 + TX, CAS number: 2415706- 16-8 + TX, CAS number: 1594624-87-9 + TX, CAS number: 1594637-65-6 + TX, CAS number: 1594626-19-3 + TX, CAS number: 1990457-52-7 + TX, CAS number: 1990457-55-0 + TX, CAS number: 1990457-57-2 + TX, CAS number: 1990457-77-6 + TX, CAS number: 1990457-66-3 + TX, CAS number: 1990457-85-6 + TX, CAS number: 2220132-55-6 + TX, CAS number: 1255091-74-7 + TX, CAS number: 2719848-60-7 + TX, CAS number: 1956329-03-5 + TX, chlorantraniliprole + TX, chlordane + TX, chlorfenapyr + TX, chloroprallethrin + TX, chromafenozide + TX, clenpirin + TX, cloethocarb + TX, clothianidin + TX, 2-chlorophenyl N-methylcarbamate (CPMC) + TX, cyanofenphos + TX, cyantraniliprole + TX, cyclaniliprole + TX, cyclobutrifluram + TX, cycloprothrin + TX, cycloxaprid + TX, cyenopyrafen + TX, cyetpyrafen (or etpyrafen) + TX, cyflumetofen + TX, cyfluthrin + TX, cyhalodiamide + TX, cyhalothrin + TX, cypermethrin + TX, cyphenothrin + TX, cyproflanilide + TX, cyromazine + TX, deltamethrin + TX, diafenthiuron + TX, dialifos + TX, dibrom + TX, dicloromezotiaz + TX, diflovidazine + TX, diflubenzuron + TX, dimpropyridaz + TX, dinactin + TX, dinocap + TX, dinotefuran + TX, dioxabenzofos + TX, emamectin (or emamectin benzoate) + TX, empenthrin + TX, epsilon - momfluorothrin + TX, epsilon-metofluthrin + TX, esfenvalerate + TX, ethion + TX, ethiprole + TX, etofenprox + TX, etoxazole + TX, famphur + TX, fenazaquin + TX, fenfluthrin + TX, , fenmezoditiaz + TX, fenitrothion + TX, fenobucarb + TX, fenothiocarb + TX, fenoxycarb + TX, fenpropathrin + TX, fenpyroximate + TX, fensulfothion + TX, fenthion + TX, fentinacetate + TX, fenvalerate + TX, fipronil + TX, flometoquin + TX, flonicamid + TX, fluacrypyrim + TX, fluazaindolizine + TX, fluazuron + TX, flubendiamide + TX, flubenzimine + TX, fluchlordiniliprole + TX, flucitrinate + TX, flucycloxuron + TX, flucythrinate + TX, fluensulfone + TX, flufenerim + TX, flufenprox + TX, flufiprole + TX, fluhexafon + TX, flumethrin + TX, fluopyram + TX, flupentiofenox + TX, flupyradifurone + TX, flupyroxystrobin + TX, flupyrimin + TX, fluralaner + TX, fluvalinate + TX, fluxametamide + TX, fosthiazate + TX, gamma- cyhalothrin + TX, guadipyr + TX, halofenozide + TX, halfenprox + TX, heptafluthrin + TX, hexythiazox + TX, hydramethylnon + TX, imicyafos + TX, imidacloprid + TX, imiprothrin + TX, indazapyroxamet + TX, indoxacarb + TX, iodomethane + TX, iprodione + TX, isocycloseram + TX, isothioate + TX, ivermectin + TX, kappa-bifenthrin + TX, kappa-tefluthrin + TX, lambda-Cyhalothrin + TX, ledprona + TX, lepimectin + TX, lotilaner + TX, lufenuron + TX, metaflumizone + TX, metaldehyde + TX, metam + TX, methomyl + TX, methoxyfenozide + TX, metofluthrin + TX, metolcarb + TX, mexacarbate + TX, milbemectin + TX, momfluorothrin + TX, niclosamide + TX, nicofluprole + TX; nitenpyram + TX, nithiazine + TX, omethoate + TX, oxamyl + TX, oxazosulfyl + TX, parathion-ethyl + TX, permethrin + TX, phenothrin + TX, phosphocarb + TX, piperonylbutoxide + TX, pirimicarb + TX, pirimiphos-ethyl + TX, pirimiphos-methyl + TX, Polyhedrosis virus + TX, prallethrin + TX, profenofos + TX, profluthrin + TX, propargite + TX, propetamphos + TX, propoxur + TX, prothiophos + TX, protrifenbute + TX, pyflubumide + TX, pymetrozine + TX, pyraclofos + TX, pyrafluprole + TX, pyridaben + TX, pyridalyl + TX, pyrifluquinazon + TX, pyrimidifen + TX, pyriminostrobin + TX, pyriprole + TX, pyriproxyfen + TX, resmethrin + TX, sarolaner + TX, selamectin + TX, silafluofen + TX, spinetoram + TX, spinosad + TX, spirobudifen + TX; spirodiclofen + TX, spiromesifen + TX, spiropidion + TX, spirotetramat + TX, spidoxamat + TX, sulfoxaflor + TX, tebufenozide + TX, tebufenpyrad + TX, tebupirimiphos + TX, tefluthrin + TX, temephos + TX, tetrachlorantraniliprole + TX, tetradiphon + TX, tetramethrin + TX, tetramethylfluthrin + TX, tetranactin + TX, tetraniliprole + TX, theta-cypermethrin + TX, thiacloprid + TX, thiamethoxam + TX, thiocyclam + TX, thiodicarb + TX, thiofanox + TX, thiometon + TX, thiosultap + TX, tigolaner + TX, tiorantraniliprole + TX; tioxazafen + TX, tolfenpyrad + TX, toxaphene + TX, tralomethrin + TX, transfluthrin + TX, triazamate + TX, triazophos + TX, trichlorfon + TX, trichloronate + TX, trichlorphon + TX, trifluenfuronate + TX, triflumezopyrim + TX, tyclopyrazoflor + TX, zeta-cypermethrin + TX, Extract of seaweed and fermentation product derived from melasse + TX, Extract of seaweed and fermentation product derived from melasse comprising urea + TX, amino acids + TX, potassium and molybdenum and EDTA-chelated manganese + TX, Extract of seaweed and fermented plant products + TX, Extract of seaweed and fermented plant products comprising phytohormones + TX, vitamins + TX, EDTA- chelated copper + TX, zinc + TX, and iron + TX, azadirachtin + TX, Bacillus aizawai + TX, Bacillus chitinosporus AQ746 (NRRL Accession No B-21618) + TX, Bacillus firmus + TX, Bacillus kurstaki + TX, Bacillus mycoides AQ726 (NRRL Accession No. B-21664) + TX, Bacillus pumilus (NRRL Accession No B-30087) + TX, Bacillus pumilus AQ717 (NRRL Accession No. B-21662) + TX, Bacillus sp. AQ178 (ATCC Accession No.53522) + TX, Bacillus sp. AQ175 (ATCC Accession No.55608) + TX, Bacillus sp. AQ177 (ATCC Accession No.55609) + TX, Bacillus subtilis unspecified + TX, Bacillus subtilis AQ153 (ATCC Accession No.55614) + TX, Bacillus subtilis AQ30002 (NRRL Accession No. B-50421) + TX, Bacillus subtilis AQ30004 (NRRL Accession No. B- 50455) + TX, Bacillus subtilis AQ713 (NRRL Accession No. B-21661) + TX, Bacillus subtilis AQ743 (NRRL Accession No. B-21665) + TX, Bacillus thuringiensis AQ52 (NRRL Accession No. B-21619) + TX, Bacillus thuringiensis BD#32 (NRRL Accession No B-21530) + TX, Bacillus thuringiensis subspec. kurstaki BMP 123 + TX, Beauveria bassiana + TX, D-limonene + TX, Granulovirus + TX, Harpin + TX, Helicoverpa armigera Nucleopolyhedrovirus + TX, Helicoverpa zea Nucleopolyhedrovirus + TX, Heliothis virescens Nucleopolyhedrovirus + TX, Heliothis punctigera Nucleopolyhedrovirus + TX, Metarhizium spp. + TX, Muscodor albus 620 (NRRL Accession No.30547) + TX, Muscodor roseus A3-5 (NRRL Accession No. 30548) + TX, Neem tree based products + TX, Paecilomyces fumosoroseus + TX, Paecilomyces lilacinus + TX, Pasteuria nishizawae + TX, Pasteuria penetrans + TX, Pasteuria ramosa + TX, Pasteuria thornei + TX, Pasteuria usgae + TX, P-cymene + TX, Plutella xylostella Granulosis virus + TX, Plutella xylostella Nucleopolyhedrovirus + TX, Polyhedrosis virus + TX, pyrethrum + TX, QRD 420 (a terpenoid blend) + TX, QRD 452 (a terpenoid blend) + TX, QRD 460 (a terpenoid blend) + TX, Quillaja saponaria + TX, Rhodococcus globerulus AQ719 (NRRL Accession No B-21663) + TX, Spodoptera frugiperda Nucleopolyhedrovirus + TX, Streptomyces galbus (NRRL Accession No.30232) + TX, Streptomyces sp. (NRRL Accession No. B-30145) + TX, Terpenoid blend + TX, and Verticillium spp. + TX; an algicide selected from the group of substances consisting of bethoxazin [CCN] + TX, copper dioctanoate (IUPAC name) (170) + TX, copper sulfate (172) + TX, cybutryne [CCN] + TX, dichlone (1052) + TX, dichlorophen (232) + TX, endothal (295) + TX, fentin (347) + TX, hydrated lime [CCN] + TX, nabam (566) + TX, quinoclamine (714) + TX, quinonamid (1379) + TX, simazine (730) + TX, triphenyltin acetate (IUPAC name) (347) + TX, and triphenyltin hydroxide (IUPAC name) (347) + TX; an anthelmintic selected from the group of substances consisting of abamectin (1) + TX, crufomate (1011) + TX, cyclobutrifluram + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ivermectin (alternative name) [CCN] + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, piperazine [CCN] + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) + TX, and thiophanate (1435) + TX; an avicide selected from the group of substances consisting of chloralose (127) + TX, endrin (1122) + TX, fenthion (346) + TX, pyridin-4-amine (IUPAC name) (23) + TX, and strychnine (745) + TX; a bactericide selected from the group of substances consisting of 1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, 8-hydroxyquinoline sulfate (446) + TX, bronopol (97) + TX, copper dioctanoate (IUPAC name) (170) + TX, copper hydroxide (IUPAC name) (169) + TX, cresol [CCN] + TX, dichlorophen (232) + TX, dipyrithione (1105) + TX, dodicin (1112) + TX, fenaminosulf (1144) + TX, formaldehyde (404) + TX, hydrargaphen (alternative name) [CCN] + TX, kasugamycin (483) + TX, kasugamycin hydrochloride hydrate (483) + TX, nickel bis(dimethyldithiocarbamate) (IUPAC name) (1308) + TX, nitrapyrin (580) + TX, octhilinone (590) + TX, oxolinic acid (606) + TX, oxytetracycline (611) + TX, potassium hydroxyquinoline sulfate (446) + TX, probenazole (658) + TX, streptomycin (744) + TX, streptomycin sesquisulfate (744) + TX, tecloftalam (766) + TX, and thiomersal (alternative name) [CCN] + TX; a biological agent selected from the group of substances consisting of Adoxophyes orana GV (alternative name) (12) + TX, Agrobacterium radiobacter (alternative name) (13) + TX, Amblyseius spp. (alternative name) (19) + TX, Anagrapha falcifera NPV (alternative name) (28) + TX, Anagrus atomus (alternative name) (29) + TX, Aphelinus abdominalis (alternative name) (33) + TX, Aphidius colemani (alternative name) (34) + TX, Aphidoletes aphidimyza (alternative name) (35) + TX, Autographa californica NPV (alternative name) (38) + TX, Bacillus firmus (alternative name) (48) + TX, Bacillus sphaericus Neide (scientific name) (49) + TX, Bacillus thuringiensis Berliner (scientific name) (51) + TX, Bacillus thuringiensis subsp. aizawai (scientific name) (51) + TX, Bacillus thuringiensis subsp. israelensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. japonensis (scientific name) (51) + TX, Bacillus thuringiensis subsp. kurstaki (scientific name) (51) + TX, Bacillus thuringiensis subsp. tenebrionis (scientific name) (51) + TX, Beauveria bassiana (alternative name) (53) + TX, Beauveria brongniartii (alternative name) (54) + TX, Chrysoperla carnea (alternative name) (151) + TX, Cryptolaemus montrouzieri (alternative name) (178) + TX, Cydia pomonella GV (alternative name) (191) + TX, Dacnusa sibirica (alternative name) (212) + TX, Diglyphus isaea (alternative name) (254) + TX, Encarsia formosa (scientific name) (293) + TX, Eretmocerus eremicus (alternative name) (300) + TX, Helicoverpa zea NPV (alternative name) (431) + TX, Heterorhabditis bacteriophora and H. megidis (alternative name) (433) + TX, Hippodamia convergens (alternative name) (442) + TX, Leptomastix dactylopii (alternative name) (488) + TX, Macrolophus caliginosus (alternative name) (491) + TX, Mamestra brassicae NPV (alternative name) (494) + TX, Metaphycus helvolus (alternative name) (522) + TX, Metarhizium anisopliae var. acridum (scientific name) (523) + TX, Metarhizium anisopliae var. anisopliae (scientific name) (523) + TX, Neodiprion sertifer NPV and N. lecontei NPV (alternative name) (575) + TX, Orius spp. (alternative name) (596) + TX, Paecilomyces fumosoroseus (alternative name) (613) + TX, Phytoseiulus persimilis (alternative name) (644) + TX, Spodoptera exigua multicapsid nuclear polyhedrosis virus (scientific name) (741) + TX, Steinernema bibionis (alternative name) (742) + TX, Steinernema carpocapsae (alternative name) (742) + TX, Steinernema feltiae (alternative name) (742) + TX, Steinernema glaseri (alternative name) (742) + TX, Steinernema riobrave (alternative name) (742) + TX, Steinernema riobravis (alternative name) (742) + TX, Steinernema scapterisci (alternative name) (742) + TX, Steinernema spp. (alternative name) (742) + TX, Trichogramma spp. (alternative name) (826) + TX, Typhlodromus occidentalis (alternative name) (844) + TX, and Verticillium lecanii (alternative name) (848) + TX; a soil sterilant selected from the group of substances consisting of iodomethane (IUPAC name) (542) + TX, and methyl bromide (537) + TX; a chemosterilant selected from the group of substances consisting of apholate [CCN] + TX, bisazir (alternative name) [CCN] + TX, busulfan (alternative name) [CCN] + TX, diflubenzuron (250) + TX, dimatif (alternative name) [CCN] + TX, hemel [CCN] + TX, hempa [CCN] + TX, metepa [CCN] + TX, methiotepa [CCN] + TX, methyl apholate [CCN] + TX, morzid [CCN] + TX, penfluron (alternative name) [CCN] + TX, tepa [CCN] + TX, thiohempa (alternative name) [CCN] + TX, thiotepa (alternative name) [CCN] + TX, tretamine (alternative name) [CCN] + TX, and uredepa (alternative name) [CCN] + TX; an insect pheromone selected from the group of substances consisting of (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol (IUPAC name) (222) + TX, (E)-tridec-4-en-1-yl acetate (IUPAC name) (829) + TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541) + TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate (IUPAC name) (779) + TX, (Z)-dodec-7-en-1-yl acetate (IUPAC name) (285) + TX, (Z)-hexadec-11-enal (IUPAC name) (436) + TX, (Z)-hexadec-11-en-1-yl acetate (IUPAC name) (437) + TX, (Z)-hexadec- 13-en-11-yn-1-yl acetate (IUPAC name) (438) + TX, (Z)-icos-13-en-10-one (IUPAC name) (448) + TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782) + TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783) + TX, (Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784) + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283) + TX, (9Z,11E)-tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780) + TX, (9Z,12E)- tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781) + TX, 14-methyloctadec-1-ene (IUPAC name) (545) + TX, 4-methylnonan-5-ol with 4-methylnonan-5-one (IUPAC name) (544) + TX, alpha- multistriatin (alternative name) [CCN] + TX, brevicomin (alternative name) [CCN] + TX, codlelure (alternative name) [CCN] + TX, codlemone (alternative name) (167) + TX, cuelure (alternative name) (179) + TX, disparlure (277) + TX, dodec-8-en-1-yl acetate (IUPAC name) (286) + TX, dodec-9-en- 1-yl acetate (IUPAC name) (287) + TX, dodeca-8 + TX, 10-dien-1-yl acetate (IUPAC name) (284) + TX, dominicalure (alternative name) [CCN] + TX, ethyl 4-methyloctanoate (IUPAC name) (317) + TX, eugenol (alternative name) [CCN] + TX, frontalin (alternative name) [CCN] + TX, Gossyplure® (alternative name; 1:1 mixture of the (Z,E) and (Z,Z) isomers of hexadeca-7,11-dien-1-yl-acetate) (420) + TX, grandlure (421) + TX, grandlure I (alternative name) (421) + TX, grandlure II (alternative name) (421) + TX, grandlure III (alternative name) (421) + TX, grandlure IV (alternative name) (421) + TX, hexalure [CCN] + TX, ipsdienol (alternative name) [CCN] + TX, ipsenol (alternative name) [CCN] + TX, japonilure (alternative name) (481) + TX, lineatin (alternative name) [CCN] + TX, litlure (alternative name) [CCN] + TX, looplure (alternative name) [CCN] + TX, medlure [CCN] + TX, megatomoic acid (alternative name) [CCN] + TX, methyl eugenol (alternative name) (540) + TX, muscalure (563) + TX, octadeca-2,13-dien-1-yl acetate (IUPAC name) (588) + TX, octadeca-3,13- dien-1-yl acetate (IUPAC name) (589) + TX, orfralure (alternative name) [CCN] + TX, oryctalure (alternative name) (317) + TX, ostramone (alternative name) [CCN] + TX, siglure [CCN] + TX, sordidin (alternative name) (736) + TX, sulcatol (alternative name) [CCN] + TX, tetradec-11-en-1-yl acetate (IUPAC name) (785) + TX, trimedlure (839) + TX, trimedlure A (alternative name) (839) + TX, trimedlure B1 (alternative name) (839) + TX, trimedlure B2 (alternative name) (839) + TX, trimedlure C (alternative name) (839) TX, and trunc-call (alternative name) [CCN] + TX; an insect repellent selected from the group of substances consisting of 2-(octylthio)ethanol (IUPAC name) (591) + TX, butopyronoxyl (933) + TX, butoxy(polypropylene glycol) (936) + TX, dibutyl adipate (IUPAC name) (1046) + TX, dibutyl phthalate (1047) + TX, dibutyl succinate (IUPAC name) (1048) + TX, diethyltoluamide [CCN] + TX, dimethyl carbate [CCN] + TX, dimethyl phthalate [CCN] + TX, ethyl hexanediol (1137) + TX, hexamide [CCN] + TX, methoquin-butyl (1276) + TX, methylneodecanamide [CCN] + TX, oxamate [CCN] + TX, and picaridin [CCN] + TX; a molluscicide selected from the group of substances consisting of bis(tributyltin) oxide (IUPAC name) (913) + TX, bromoacetamide [CCN] + TX, calcium arsenate [CCN] + TX, cloethocarb (999) + TX, copper acetoarsenite [CCN] + TX, copper sulfate (172) + TX, fentin (347) + TX, ferric phosphate (IUPAC name) (352) + TX, metaldehyde (518) + TX, methiocarb (530) + TX, niclosamide (576) + TX, niclosamide-olamine (576) + TX, pentachlorophenol (623) + TX, sodium pentachlorophenoxide (623) + TX, tazimcarb (1412) + TX, thiodicarb (799) + TX, tributyltin oxide (913) + TX, trifenmorph (1454) + TX, trimethacarb (840) + TX, triphenyltin acetate (IUPAC name) (347) + TX, triphenyltin hydroxide (IUPAC name) (347) + TX, and pyriprole [394730-71-3] + TX; a nematicide selected from the group of substances consisting of AKD-3088 (compound code) + TX, 1,2-dibromo-3-chloropropane (IUPAC/Chemical Abstracts name) (1045) + TX, 1,2-dichloropropane (IUPAC/ Chemical Abstracts name) (1062) + TX, 1,2-dichloropropane with 1,3-dichloropropene (IUPAC name) (1063) + TX, 1,3-dichloropropene (233) + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC/Chemical Abstracts name) (1065) + TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980) + TX, 5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid (IUPAC name) (1286) + TX, 6- isopentenylaminopurine (alternative name) (210) + TX, abamectin (1) + TX, acetoprole [CCN] + TX, alanycarb (15) + TX, aldicarb (16) + TX, aldoxycarb (863) + TX, AZ 60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (alternative name) + TX, cadusafos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, carbosulfan (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, cloethocarb (999) + TX, cyclobutrifluram + TX, cytokinins (alternative name) (210) + TX, dazomet (216) + TX, DBCP (1045) + TX, DCIP (218) + TX, diamidafos (1044) + TX, dichlofenthion (1051) + TX, dicliphos (alternative name) + TX, dimethoate (262) + TX, doramectin (alternative name) [CCN] + TX, emamectin (291) + TX, emamectin benzoate (291) + TX, eprinomectin (alternative name) [CCN] + TX, ethoprophos (312) + TX, ethylene dibromide (316) + TX, fenamiphos (326) + TX, fenpyrad (alternative name) + TX, fensulfothion (1158) + TX, fosthiazate (408) + TX, fosthietan (1196) + TX, furfural (alternative name) [CCN] + TX, GY-81 (development code) (423) + TX, heterophos [CCN] + TX, iodomethane (IUPAC name) (542) + TX, isamidofos (1230) + TX, isazofos (1231) + TX, ivermectin (alternative name) [CCN] + TX, kinetin (alternative name) (210) + TX, mecarphon (1258) + TX, metam (519) + TX, metam-potassium (alternative name) (519) + TX, metam-sodium (519) + TX, methyl bromide (537) + TX, methyl isothiocyanate (543) + TX, milbemycin oxime (alternative name) [CCN] + TX, moxidectin (alternative name) [CCN] + TX, Myrothecium verrucaria composition (alternative name) (565) + TX, NC-184 (compound code) + TX, oxamyl (602) + TX, phorate (636) + TX, phosphamidon (639) + TX, phosphocarb [CCN] + TX, sebufos (alternative name) + TX, selamectin (alternative name) [CCN] + TX, spinosad (737) + TX, terbam (alternative name) + TX, terbufos (773) + TX, tetrachlorothiophene (IUPAC/ Chemical Abstracts name) (1422) + TX, thiafenox (alternative name) + TX, thionazin (1434) + TX, triazophos (820) + TX, triazuron (alternative name) + TX, xylenols [CCN] + TX, YI-5302 (compound code) + TX, zeatin (alternative name) (210) + TX, fluensulfone [318290-98-1] + TX, and fluopyram + TX; a nitrification inhibitor selected from the group of substances consisting of potassium ethylxanthate [CCN] + TX, and nitrapyrin (580) + TX; a plant activator selected from the group of substances consisting of acibenzolar (6) + TX, acibenzolar- S-methyl (6) + TX, probenazole (658) + TX, and Reynoutria sachalinensis extract (alternative name) (720) + TX; a rodenticide selected from the group of substances consisting of 2-isovalerylindan-1,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, alpha- chlorohydrin [CCN] + TX, aluminium phosphide (640) + TX, antu (880) + TX, arsenous oxide (882) + TX, barium carbonate (891) + TX, bisthiosemi (912) + TX, brodifacoum (89) + TX, bromadiolone (including alpha-bromadiolone) + TX, bromethalin (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chlorophacinone (140) + TX, cholecalciferol (alternative name) (850) + TX, coumachlor (1004) + TX, coumafuryl (1005) + TX, coumatetralyl (175) + TX, crimidine (1009) + TX, difenacoum (246) + TX, difethialone (249) + TX, diphacinone (273) + TX, ergocalciferol (301) + TX, flocoumafen (357) + TX, fluoroacetamide (379) + TX, flupropadine (1183) + TX, flupropadine hydrochloride (1183) + TX, gamma-HCH (430) + TX, HCH (430) + TX, hydrogen cyanide (444) + TX, iodomethane (IUPAC name) (542) + TX, lindane (430) + TX, magnesium phosphide (IUPAC name) (640) + TX, methyl bromide (537) + TX, norbormide (1318) + TX, phosacetim (1336) + TX, phosphine (IUPAC name) (640) + TX, phosphorus [CCN] + TX, pindone (1341) + TX, potassium arsenite [CCN] + TX, pyrinuron (1371) + TX, scilliroside (1390) + TX, sodium arsenite [CCN] + TX, sodium cyanide (444) + TX, sodium fluoroacetate (735) + TX, strychnine (745) + TX, thallium sulfate [CCN] + TX, warfarin (851) + TX, and zinc phosphide (640) + TX; a synergist selected from the group of substances consisting of 2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934) + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903) + TX, farnesol with nerolidol (alternative name) (324) + TX, MB-599 (development code) (498) + TX, MGK 264 (development code) (296) + TX, piperonyl butoxide (649) + TX, piprotal (1343) + TX, propyl isomer (1358) + TX, S421 (development code) (724) + TX, sesamex (1393) + TX, sesasmolin (1394) + TX, and sulfoxide (1406) + TX; an animal repellent selected from the group of substances consisting of anthraquinone (32) + TX, chloralose (127) + TX, copper naphthenate [CCN] + TX, copper oxychloride (171) + TX, diazinon (227) + TX, dicyclopentadiene (chemical name) (1069) + TX, guazatine (422) + TX, guazatine acetates (422) + TX, methiocarb (530) + TX, pyridin-4-amine (IUPAC name) (23) + TX, thiram (804) + TX, trimethacarb (840) + TX, zinc naphthenate [CCN] + TX, and ziram (856) + TX; a virucide selected from the group of substances consisting of imanin (alternative name) [CCN] and ribavirin (alternative name) [CCN] + TX; a wound protectant selected from the group of substances consisting of mercuric oxide (512) + TX, octhilinone (590) + TX, and thiophanate-methyl (802) + TX; a biologically active substance selected from 1,1-bis(4-chloro-phenyl)-2-ethoxyethanol + TX, 2,4- dichlorophenyl benzenesulfonate + TX, 2-fluoro-N-methyl-N-1-naphthylacetamide + TX, 4-chlorophenyl phenyl sulfone + TX, acetoprole + TX, aldoxycarb + TX, amidithion + TX, amidothioate + TX, amiton + TX, amiton hydrogen oxalate + TX, amitraz + TX, aramite + TX, arsenous oxide + TX, azobenzene + TX, azothoate + TX, benomyl + TX, benoxa-fos + TX, benzyl benzoate + TX, bixafen + TX, brofenvalerate + TX, bromo-cyclen + TX, bromophos + TX, bromopropylate + TX, buprofezin + TX, butocarboxim + TX, butoxycarboxim + TX, butylpyridaben + TX, calcium polysulfide + TX, camphechlor + TX, carbanolate + TX, carbophenothion + TX, cymiazole + TX, chino-methionat + TX, chlorbenside + TX, chlordimeform + TX, chlordimeform hydrochloride + TX, chlorfenethol + TX, chlorfenson + TX, chlorfensulfide + TX, chlorobenzilate + TX, chloromebuform + TX, chloromethiuron + TX, chloropropylate + TX, chlorthiophos + TX, cinerin I + TX, cinerin II + TX, cinerins + TX, closantel + TX, coumaphos + TX, crotamiton + TX, crotoxyphos + TX, cufraneb + TX, cyanthoate + TX, DCPM + TX, DDT + TX, demephion + TX, demephion-O + TX, demephion-S + TX, demeton-methyl + TX, demeton- O + TX, demeton-O-methyl + TX, demeton-S + TX, demeton-S-methyl + TX, demeton-S-methylsulfon + TX, dichlofluanid + TX, dichlorvos + TX, dicliphos + TX, dienochlor + TX, dimefox + TX, dinex + TX, dinex-diclexine + TX, dinocap-4 + TX, dinocap-6 + TX, dinocton + TX, dino-penton + TX, dinosulfon + TX, dinoterbon + TX, dioxathion + TX, diphenyl sulfone + TX, disulfiram + TX, DNOC + TX, dofenapyn + TX, doramectin + TX, endothion + TX, eprinomectin + TX, ethoate-methyl + TX, etrimfos + TX, fenazaflor + TX, fenbutatin oxide + TX, fenothiocarb + TX, fenpyrad + TX, fen-pyroximate + TX, fenpyrazamine + TX, fenson + TX, fentrifanil + TX, flubenzimine + TX, flucycloxuron + TX, fluenetil + TX, fluorbenside + TX, FMC 1137 + TX, formetanate + TX, formetanate hydrochloride + TX, formparanate + TX, gamma-HCH + TX, glyodin + TX, halfenprox + TX, hexadecyl cyclopropanecarboxylate + TX, isocarbophos + TX, jasmolin I + TX, jasmolin II + TX, jodfenphos + TX, lindane + TX, malonoben + TX, mecarbam + TX, mephosfolan + TX, mesulfen + TX, methacrifos + TX, methyl bromide + TX, metolcarb + TX, mexacarbate + TX, milbemycin oxime + TX, mipafox + TX, monocrotophos + TX, morphothion + TX, moxidectin + TX, naled + TX, 4-chloro-2-(2-chloro-2-methyl- propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one + TX, nifluridide + TX, nikkomycins + TX, nitrilacarb + TX, nitrilacarb 1:1 zinc chloride complex + TX, omethoate + TX, oxydeprofos + TX, oxydisulfoton + TX, pp'-DDT + TX, parathion + TX, permethrin + TX, phenkapton + TX, phosalone + TX, phosfolan + TX, phosphamidon + TX, polychloroterpenes + TX, polynactins + TX, proclonol + TX, promacyl + TX, propoxur + TX, prothidathion + TX, prothoate + TX, pyrethrin I + TX, pyrethrin II + TX, pyrethrins + TX, pyridaphenthion + TX, pyrimitate + TX, quinalphos + TX, quintiofos + TX, R-1492 + TX, phosglycin + TX, rotenone + TX, schradan + TX, sebufos + TX, selamectin + TX, sophamide + TX, SSI- 121 + TX, sulfiram + TX, sulfluramid + TX, sulfotep + TX, sulfur + TX, diflovidazin + TX, tau-fluvalinate + TX, TEPP + TX, terbam + TX, tetradifon + TX, tetrasul + TX, thiafenox + TX, thiocarboxime + TX, thiofanox + TX, thiometon + TX, thioquinox + TX, thuringiensin + TX, triamiphos + TX, triarathene + TX, triazophos + TX, triazuron + TX, trifenofos + TX, trinactin + TX, vamidothion + TX, vaniliprole + TX, bethoxazin + TX, copper dioctanoate + TX, copper sulfate + TX, cybutryne + TX, dichlone + TX, dichlorophen + TX, endothal + TX, fentin + TX, hydrated lime + TX, nabam + TX, quinoclamine + TX, quinonamid + TX, simazine + TX, triphenyltin acetate + TX, triphenyltin hydroxide + TX, crufomate + TX, piperazine + TX, thiophanate + TX, chloralose + TX, fenthion + TX, pyridin-4-amine + TX, strychnine + TX, 1-hydroxy-1H-pyridine-2-thione + TX, 4-(quinoxalin-2-ylamino)benzenesulfonamide + TX, 8- hydroxyquinoline sulfate + TX, bronopol + TX, copper hydroxide + TX, cresol + TX, dipyrithione + TX, dodicin + TX, fenaminosulf + TX, formaldehyde + TX, hydrargaphen + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, nickel bis(dimethyldithiocarbamate) + TX, nitrapyrin + TX, octhilinone + TX, oxolinic acid + TX, oxytetracycline + TX, potassium hydroxyquinoline sulfate + TX, probenazole + TX, streptomycin + TX, streptomycin sesquisulfate + TX, tecloftalam + TX, thiomersal + TX, Adoxophyes orana GV + TX, Agrobacterium radiobacter + TX, Amblyseius spp. + TX, Anagrapha falcifera NPV + TX, Anagrus atomus + TX, Aphelinus abdominalis + TX, Aphidius colemani + TX, Aphidoletes aphidimyza + TX, Autographa californica NPV + TX, Bacillus sphaericus Neide + TX, Beauveria brongniartii + TX, Chrysoperla carnea + TX, Cryptolaemus montrouzieri + TX, Cydia pomonella GV + TX, Dacnusa sibirica + TX, Diglyphus isaea + TX, Encarsia formosa + TX, Eretmocerus eremicus + TX, Heterorhabditis bacteriophora and H. megidis + TX, Hippodamia convergens + TX, Leptomastix dactylopii + TX, Macrolophus caliginosus + TX, Mamestra brassicae NPV + TX, Metaphycus helvolus + TX, Metarhizium anisopliae var. acridum + TX, Metarhizium anisopliae var. anisopliae + TX, Neodiprion sertifer NPV and N. lecontei NPV + TX, Orius spp. + TX, Paecilomyces fumosoroseus + TX, Phytoseiulus persimilis + TX, Steinernema bibionis + TX, Steinernema carpocapsae + TX, Steinernema feltiae + TX, Steinernema glaseri + TX, Steinernema riobrave + TX, Steinernema riobravis + TX, Steinernema scapterisci + TX, Steinernema spp. + TX, Trichogramma spp. + TX, Typhlodromus occidentalis + TX , Verticillium lecanii + TX, apholate + TX, bisazir + TX, busulfan + TX, dimatif + TX, hemel + TX, hempa + TX, metepa + TX, methiotepa + TX, methyl apholate + TX, morzid + TX, penfluron + TX, tepa + TX, thiohempa + TX, thiotepa + TX, tretamine + TX, uredepa + TX, (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol + TX, (E)-tridec-4-en-1-yl acetate + TX, (E)-6- methylhept-2-en-4-ol + TX, (E,Z)-tetradeca-4,10-dien-1-yl acetate + TX, (Z)-dodec-7-en-1-yl acetate + TX, (Z)-hexadec-11-enal + TX, (Z)-hexadec-11-en-1-yl acetate + TX, (Z)-hexadec-13-en-11-yn-1-yl acetate + TX, (Z)-icos-13-en-10-one + TX, (Z)-tetradec-7-en-1-al + TX, (Z)-tetradec-9-en-1-ol + TX, (Z)- tetradec-9-en-1-yl acetate + TX, (7E,9Z)-dodeca-7,9-dien-1-yl acetate + TX, (9Z,11E)-tetradeca-9,11- dien-1-yl acetate + TX, (9Z,12E)-tetradeca-9,12-dien-1-yl acetate + TX, 14-methyloctadec-1-ene + TX, 4-methylnonan-5-ol with 4-methylnonan-5-one + TX, alpha-multistriatin + TX, brevicomin + TX, codlelure + TX, codlemone + TX, cuelure + TX, disparlure + TX, dodec-8-en-1-yl acetate + TX, dodec-9-en-1-yl acetate + TX, dodeca-8 + TX, 10-dien-1-yl acetate + TX, dominicalure + TX, ethyl 4-methyloctanoate + TX, eugenol + TX, frontalin + TX, grandlure + TX, grandlure I + TX, grandlure II + TX, grandlure III + TX, grandlure IV + TX, hexalure + TX, ipsdienol + TX, ipsenol + TX, japonilure + TX, lineatin + TX, litlure + TX, looplure + TX, medlure + TX, megatomoic acid + TX, methyl eugenol + TX, muscalure + TX, octadeca-2,13-dien-1-yl acetate + TX, octadeca-3,13-dien-1-yl acetate + TX, orfralure + TX, oryctalure + TX, ostramone + TX, siglure + TX, sordidin + TX, sulcatol + TX, tetradec-11-en-1-yl acetate + TX, trimedlure + TX, trimedlure A + TX, trimedlure B1 + TX, trimedlure B2 + TX, trimedlure C + TX, trunc-call + TX, 2-(octylthio)-ethanol + TX, butopyronoxyl + TX, butoxy(polypropylene glycol) + TX, dibutyl adipate + TX, dibutyl phthalate + TX, dibutyl succinate + TX, diethyltoluamide + TX, dimethyl carbate + TX, dimethyl phthalate + TX, ethyl hexanediol + TX, hexamide + TX, methoquin-butyl + TX, methylneodecanamide + TX, oxamate + TX, picaridin + TX, 1-dichloro-1-nitroethane + TX, 1,1-dichloro- 2,2-bis(4-ethylphenyl)-ethane + TX, 1,2-dichloropropane with 1,3-dichloropropene + TX, 1-bromo-2- chloroethane + TX, 2,2,2-trichloro-1-(3,4-dichloro-phenyl)ethyl acetate + TX, 2,2-dichlorovinyl 2- ethylsulfinylethyl methyl phosphate + TX, 2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate + TX, 2-(2- butoxyethoxy)ethyl thiocyanate + TX, 2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate + TX, 2-(4-chloro-3,5-xylyloxy)ethanol + TX, 2-chlorovinyl diethyl phosphate + TX, 2-imidazolidone + TX, 2- isovalerylindan-1,3-dione + TX, 2-methyl(prop-2-ynyl)aminophenyl methylcarbamate + TX, 2- thiocyanatoethyl laurate + TX, 3-bromo-1-chloroprop-1-ene + TX, 3-methyl-1-phenylpyrazol-5-yl dimethyl-carbamate + TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl methylcarbamate + TX, 5,5-dimethyl-3- oxocyclohex-1-enyl dimethylcarbamate + TX, acethion + TX, acrylonitrile + TX, aldrin + TX, allosamidin + TX, allyxycarb + TX, alpha-ecdysone + TX, aluminium phosphide + TX, aminocarb + TX, anabasine + TX, athidathion + TX, azamethiphos + TX, Bacillus thuringiensis delta endotoxins + TX, barium hexafluorosilicate + TX, barium polysulfide + TX, barthrin + TX, Bayer 22/190 + TX, Bayer 22408 + TX, beta-cyfluthrin + TX, beta-cypermethrin + TX, bioethanomethrin + TX, biopermethrin + TX, bis(2- chloroethyl) ether + TX, borax + TX, bromfenvinfos + TX, bromo-DDT + TX, bufencarb + TX, butacarb + TX, butathiofos + TX, butonate + TX, calcium arsenate + TX, calcium cyanide + TX, carbon disulfide + TX, carbon tetrachloride + TX, cartap hydrochloride + TX, cevadine + TX, chlorbicyclen + TX, chlordane + TX, chlordecone + TX, chloroform + TX, chloropicrin + TX, chlorphoxim + TX, chlorprazophos + TX, cis-resmethrin + TX, cismethrin + TX, clocythrin + TX, copper acetoarsenite + TX, copper arsenate + TX, copper oleate + TX, coumithoate + TX, cryolite + TX, CS 708 + TX, cyanofenphos + TX, cyanophos + TX, cyclethrin + TX, cythioate + TX, d-tetramethrin + TX, DAEP + TX, dazomet + TX, decarbofuran + TX, diamidafos + TX, dicapthon + TX, dichlofenthion + TX, dicresyl + TX, dicyclanil + TX, dieldrin + TX, diethyl 5-methylpyrazol-3-yl phosphate + TX, dilor + TX, dimefluthrin + TX, dimetan + TX, dimethrin + TX, dimethylvinphos + TX, dimetilan + TX, dinoprop + TX, dinosam + TX, dinoseb + TX, diofenolan + TX, dioxabenzofos + TX, dithicrofos + TX, DSP + TX, ecdysterone + TX, EI 1642 + TX, EMPC + TX, EPBP + TX, etaphos + TX, ethiofencarb + TX, ethyl formate + TX, ethylene dibromide + TX, ethylene dichloride + TX, ethylene oxide + TX, EXD + TX, fenchlorphos + TX, fenethacarb + TX, fenitrothion + TX, fenoxacrim + TX, fenpirithrin + TX, fensulfothion + TX, fenthion-ethyl + TX, flucofuron + TX, fosmethilan + TX, fospirate + TX, fosthietan + TX, furathiocarb + TX, furethrin + TX, guazatine + TX, guazatine acetates + TX, sodium tetrathiocarbonate + TX, halfenprox + TX, HCH + TX, HEOD + TX, heptachlor + TX, heterophos + TX, HHDN + TX, hydrogen cyanide + TX, hyquincarb + TX, IPSP + TX, isazofos + TX, isobenzan + TX, isodrin + TX, isofenphos + TX, isolane + TX, isoprothiolane + TX, isoxathion + TX, juvenile hormone I + TX, juvenile hormone II + TX, juvenile hormone III + TX, kelevan + TX, kinoprene + TX, lead arsenate + TX, leptophos + TX, lirimfos + TX, lythidathion + TX, m-cumenyl methylcarbamate + TX, magnesium phosphide + TX, mazidox + TX, mecarphon + TX, menazon + TX, mercurous chloride + TX, mesulfenfos + TX, metam + TX, metam-potassium + TX, metam-sodium + TX, methanesulfonyl fluoride + TX, methocrotophos + TX, methoprene + TX, methothrin + TX, methoxychlor + TX, methyl isothiocyanate + TX, methylchloroform + TX, methylene chloride + TX, metoxadiazone + TX, mirex + TX, naftalofos + TX, naphthalene + TX, NC-170 + TX, nicotine + TX, nicotine sulfate + TX, nithiazine + TX, nornicotine + TX, O-5-dichloro-4-iodophenyl O-ethyl ethylphosphonothioate + TX, O,O-diethyl O-4-methyl-2-oxo-2H-chromen-7-yl phosphorothioate + TX, O,O-diethyl O-6-methyl-2-propylpyrimidin-4-yl phosphorothioate + TX, O,O,O',O'-tetrapropyl dithiopyrophosphate + TX, oleic acid + TX, para-dichlorobenzene + TX, parathion-methyl + TX, pentachlorophenol + TX, pentachlorophenyl laurate + TX, PH 60-38 + TX, phenkapton + TX, phosnichlor + TX, phosphine + TX, phoxim-methyl + TX, pirimetaphos + TX, polychlorodicyclopentadiene isomers + TX, potassium arsenite + TX, potassium thiocyanate + TX, precocene I + TX, precocene II + TX, precocene III + TX, primidophos + TX, profluthrin + TX, promecarb + TX, prothiofos + TX, pyrazophos + TX, pyresmethrin + TX, quassia + TX, quinalphos-methyl + TX, quinothion + TX, rafoxanide + TX, resmethrin + TX, rotenone + TX, kadethrin + TX, ryania + TX, ryanodine + TX, sabadilla + TX, schradan + TX, sebufos + TX, SI-0009 + TX, thiapronil + TX, sodium arsenite + TX, sodium cyanide + TX, sodium fluoride + TX, sodium hexafluorosilicate + TX, sodium pentachlorophenoxide + TX, sodium selenate + TX, sodium thiocyanate + TX, sulcofuron + TX, sulcofuron-sodium + TX, sulfuryl fluoride + TX, sulprofos + TX, tar oils + TX, tazimcarb + TX, TDE + TX, tebupirimfos + TX, temephos + TX, terallethrin + TX, tetrachloroethane + TX, thicrofos + TX, thiocyclam + TX, thiocyclam hydrogen oxalate + TX, thionazin + TX, thiosultap + TX, thiosultap-sodium + TX, tralomethrin + TX, transpermethrin + TX, triazamate + TX, trichlormetaphos-3 + TX, trichloronat + TX, trimethacarb + TX, tolprocarb + TX, triclopyricarb + TX, triprene + TX, veratridine + TX, veratrine + TX, XMC + TX, zetamethrin + TX, zinc phosphide + TX, zolaprofos + TX, meperfluthrin + TX, tetramethylfluthrin + TX, bis(tributyltin) oxide + TX, bromoacetamide + TX, ferric phosphate + TX, niclosamide-olamine + TX, tributyltin oxide + TX, pyrimorph + TX, trifenmorph + TX, 1,2-dibromo-3-chloropropane + TX, 1,3-dichloropropene + TX, 3,4- dichlorotetrahydrothio-phene 1,1-dioxide + TX, 3-(4-chlorophenyl)-5-methylrhodanine + TX, 5-methyl-6- thioxo-1,3,5-thiadiazinan-3-ylacetic acid + TX, 6-isopentenylaminopurine + TX, anisiflupurin + TX, benclothiaz + TX, cytokinins + TX, DCIP + TX, furfural + TX, isamidofos + TX, kinetin + TX, Myrothecium verrucaria composition + TX, tetrachlorothiophene + TX, xylenols + TX, zeatin + TX, potassium ethylxanthate + TX ,acibenzolar + TX, acibenzolar-S-methyl + TX, Reynoutria sachalinensis extract + TX, alpha-chlorohydrin + TX, antu + TX, barium carbonate + TX, bisthiosemi + TX, brodifacoum + TX, bromadiolone + TX, bromethalin + TX, chlorophacinone + TX, cholecalciferol + TX, coumachlor + TX, coumafuryl + TX, coumatetralyl + TX, crimidine + TX, difenacoum + TX, difethialone + TX, diphacinone + TX, ergocalciferol + TX, flocoumafen + TX, fluoroacetamide + TX, flupropadine + TX, flupropadine hydrochloride + TX, norbormide + TX, phosacetim + TX, phosphorus + TX, pindone + TX, pyrinuron + TX, scilliroside + TX, -sodium fluoroacetate + TX, thallium sulfate + TX, warfarin + TX, -2-(2- butoxyethoxy)ethyl piperonylate + TX, 5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone + TX, farnesol with nerolidol + TX, verbutin + TX, MGK 264 + TX, piperonyl butoxide + TX, piprotal + TX, propyl isomer + TX, S421 + TX, sesamex + TX, sesasmolin + TX, sulfoxide + TX, anthraquinone + TX, copper naphthenate + TX, copper oxychloride + TX, dicyclopentadiene + TX, thiram + TX, zinc naphthenate + TX, ziram + TX, imanin + TX, ribavirin + TX, chloroinconazide + TX, mercuric oxide + TX, thiophanate- methyl + TX, azaconazole + TX, bitertanol + TX, bromuconazole + TX, cyproconazole + TX, difenoconazole + TX, diniconazole -+ TX, epoxiconazole + TX, fenbuconazole + TX, fluquinconazole + TX, flusilazole + TX, flutriafol + TX, furametpyr + TX, hexaconazole + TX, imazalil- + TX, imiben-conazole + TX, ipconazole + TX, metconazole + TX, myclobutanil + TX, paclobutrazole + TX, pefurazoate + TX, penconazole + TX, prothioconazole + TX, pyrifenox + TX, prochloraz + TX, propiconazole + TX, pyrisoxazole + TX, -simeconazole + TX, tebucon-azole + TX, tetraconazole + TX, triadimefon + TX, triadimenol + TX, triflumizole + TX, triticonazole + TX, ancymidol + TX, fenarimol + TX, nuarimol + TX, bupirimate + TX, dimethirimol + TX, ethirimol + TX, dodemorph + TX, fenpropidin + TX, fenpropimorph + TX, spiroxamine + TX, tridemorph + TX, cyprodinil + TX, mepanipyrim + TX, pyrimethanil + TX, fenpiclonil + TX, fludioxonil + TX, benalaxyl + TX, furalaxyl + TX, metalaxyl + TX, R- metalaxyl + TX, ofurace + TX, oxadixyl + TX, carbendazim + TX, debacarb + TX, fuberidazole -+ TX, thiabendazole + TX, chlozolinate + TX, dichlozoline + TX, myclozoline- + TX, procymidone + TX, vinclozoline + TX, boscalid + TX, carboxin + TX, fenfuram + TX, flutolanil + TX, mepronil + TX, oxycarboxin + TX, penthiopyrad + TX, thifluzamide + TX, dodine + TX, iminoctadine + TX, azoxystrobin + TX, dimoxystrobin + TX, enestroburin + TX, fenaminstrobin + TX, flufenoxystrobin + TX, fluoxastrobin + TX, kresoxim--methyl + TX, metominostrobin + TX, trifloxystrobin + TX, orysastrobin + TX, picoxystrobin + TX, pyraclostrobin + TX, pyrametostrobin + TX, pyraoxystrobin + TX, ferbam + TX, mancozeb + TX, maneb + TX, metiram + TX, propineb + TX, zineb + TX, captafol + TX, captan + TX, fluoroimide + TX, folpet + TX, tolylfluanid + TX, bordeaux mixture + TX, copper oxide + TX, mancopper + TX, oxine-copper + TX, nitrothal-isopropyl + TX, edifenphos + TX, iprobenphos + TX, phosdiphen + TX, tolclofos-methyl + TX, anilazine + TX, benthiavalicarb + TX, blasticidin-S + TX, chloroneb -+ TX, chloro-tha-lonil + TX, cyflufenamid + TX, cymoxanil + TX, cyclobutrifluram + TX, diclocymet + TX, diclomezine + TX, dicloran + TX, diethofencarb + TX, dimethomorph -+ TX, flumorph + TX, dithianon + TX, ethaboxam + TX, etridiazole + TX, famoxadone + TX, fenamidone + TX, fenoxanil + TX, ferimzone + TX, fluazinam + TX, flumetylsulforim + TX, fluopicolide + TX, fluoxytioconazole + TX, flusulfamide + TX, fluxapyroxad + TX, fenhexamid + TX, fosetyl-aluminium -+ TX, hymexazol + TX, iprovalicarb + TX, cyazofamid + TX, methasulfocarb + TX, metrafenone + TX, pencycuron + TX, phthalide + TX, polyoxins + TX, propamocarb + TX, pyribencarb + TX, proquinazid + TX, pyroquilon + TX, pyriofenone + TX, quinoxyfen + TX, quintozene + TX, tiadinil + TX, triazoxide + TX, tricyclazole + TX, triforine + TX, validamycin + TX, valifenalate + TX, zoxamide + TX, mandipropamid + TX, flubeneteram + TX, isopyrazam + TX, sedaxane + TX, benzovindiflupyr + TX, pydiflumetofen + TX, 3-difluoromethyl-1- methyl-1H-pyrazole-4-carboxylic acid (3',4',5'-trifluoro-biphenyl-2-yl)-amide + TX, isoflucypram + TX, isotianil + TX, dipymetitrone + TX, 6-ethyl-5,7-dioxo-pyrrolo[4,5][1,4]dithiino[1,2-c]isothiazole-3- carbonitrile + TX, 2-(difluoromethyl)-N-[3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, 4- (2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazine-3-carbonitrile + TX, (R)-3-(difluoromethyl)-1-methyl- N-[1,1,3-trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 4-(2-bromo-4-fluoro-phenyl)-N-(2-chloro-6- fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine + TX, 4- (2- bromo- 4- fluorophenyl) - N- (2- chloro- 6- fluorophenyl) - 1, 3- dimethyl- 1H- pyrazol- 5- amine + TX, fluindapyr + TX, coumethoxystrobin (jiaxiangjunzhi) + TX, lvbenmixianan + TX, dichlobentiazox + TX, mandestrobin + TX, 3-(4,4-difluoro- 3,4-dihydro-3,3-dimethylisoquinolin-1-yl)quinolone + TX, 2-[2-fluoro-6-[(8-fluoro-2-methyl-3- quinolyl)oxy]phenyl]propan-2-ol + TX, oxathiapiprolin + TX, tert-butyl N-[6-[[[(1-methyltetrazol-5-yl)- phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate + TX, pyraziflumid + TX, inpyrfluxam + TX, trolprocarb + TX, mefentrifluconazole + TX, ipfentrifluconazole+ TX, 2-(difluoromethyl)-N-[(3R)-3-ethyl- 1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX, N'-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N- methyl-formamidine + TX, N'-[4-(4,5-dichlorothiazol-2-yl)oxy-2,5-dimethyl-phenyl]-N-ethyl-N-methyl- formamidine + TX, [2-[3-[2-[1-[2-[3,5-bis(difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]thiazol-4-yl]-4,5- dihydroisoxazol-5-yl]-3-chloro-phenyl] methanesulfonate + TX, but-3-ynyl N-[6-[[(Z)-[(1-methyltetrazol- 5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate + TX, methyl N-[[5-[4-(2,4- dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamate + TX, 3-chloro-6-methyl-5-phenyl-4- (2,4,6-trifluorophenyl)pyridazine + TX, pyridachlometyl + TX, 3-(difluoromethyl)-1-methyl-N-[1,1,3- trimethylindan-4-yl]pyrazole-4-carboxamide + TX, 1-[2-[[1-(4-chlorophenyl)pyrazol-3-yl]oxymethyl]-3- methyl-phenyl]-4-methyl-tetrazol-5-one + TX, 1-methyl-4-[3-methyl-2-[[2-methyl-4-(3,4,5- trimethylpyrazol-1-yl)phenoxy]methyl]phenyl]tetrazol-5-one + TX, aminopyrifen + TX, ametoctradin + TX, amisulbrom + TX, penflufen + TX, (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino- N,3-dimethyl-pent-3-enamide + TX, florylpicoxamid + TX, fenpicoxamid + TX, metarylpicoxamid + TX, tebufloquin + TX, ipflufenoquin + TX, quinofumelin + TX, isofetamid + TX, ethyl 1-[[4-[[2-(trifluoromethyl)- 1,3-dioxolan-2-yl]methoxy]phenyl]methyl]pyrazole-3-carboxylate + TX (may be prepared from the methods described in WO 2020/056090), ethyl 1-[[4-[(Z)-2-ethoxy-3,3,3-trifluoro-prop-1- enoxy]phenyl]methyl]pyrazole-3-carboxylate + TX (may be prepared from the methods described in WO 2020/056090), methyl N-[[4-[1-(4-cyclopropyl-2,6-difluoro-phenyl)pyrazol-4-yl]-2-methyl- phenyl]methyl]carbamate + TX (may be prepared from the methods described in WO 2020/097012), methyl N-[[4-[1-(2,6-difluoro-4-isopropyl-phenyl)pyrazol-4-yl]-2-methyl-phenyl]methyl]carbamate + TX (may be prepared from the methods described in WO 2020/097012), 6-chloro-3-(3-cyclopropyl-2-fluoro- phenoxy)-N-[2-(2,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide + TX (may be prepared from the methods described in WO 2020/109391), 6-chloro-N-[2-(2-chloro-4-methyl- phenyl)-2,2-difluoro-ethyl]-3-(3-cyclopropyl-2-fluoro-phenoxy)-5-methyl-pyridazine-4-carboxamide + TX (may be prepared from the methods described in WO 2020/109391), 6-chloro-3-(3-cyclopropyl-2-fluoro- phenoxy)-N-[2-(3,4-dimethylphenyl)-2,2-difluoro-ethyl]-5-methyl-pyridazine-4-carboxamide + TX (may be prepared from the methods described in WO 2020/109391), N-[2-[2,4-dichloro-phenoxy]phenyl]-3- (difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, N-[2-[2-chloro-4- (trifluoromethyl)phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX, benzothiostrobin + TX, phenamacril + TX, 5-amino-1,3,4-thiadiazole-2-thiol zinc salt (2:1) + TX, fluopyram + TX, flufenoxadiazam + TX, flutianil + TX, fluopimomide + TX, pyrapropoyne + TX, picarbutrazox + TX, 2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indan-4-yl)pyridine-3-carboxamide + TX, 2- (difluoromethyl) - N- ((3R) - 1, 1, 3- trimethylindan- 4- yl) pyridine- 3- carboxamide + TX, 4-[[6-[2-(2,4- difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX, metyltetraprole + TX, 2- (difluoromethyl) - N- ((3R) - 1, 1, 3- trimethylindan- 4- yl) pyridine- 3- carboxamide + TX, α- (1, 1- dimethylethyl) - α- [4'- (trifluoromethoxy) [1, 1'- biphenyl] - 4- yl] -5- pyrimidinemethanol + TX, fluoxapiprolin + TX, enoxastrobin + TX, methyl (Z)-3-methoxy-2-[2-methyl-5- [4-(trifluoromethyl)triazol-2-yl]phenoxy]prop-2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-(4- propyltriazol-2-yl)phenoxy]prop-2-enoate + TX, methyl (Z)-2-[5-(3-isopropylpyrazol-1-yl)-2-methyl- phenoxy]-3-methoxy-prop-2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-(3-propylpyrazol-1- yl)phenoxy]prop-2-enoate + TX, methyl (Z)-3-methoxy-2-[2-methyl-5-[3-(trifluoromethyl)pyrazol-1- yl]phenoxy]prop-2-enoate + TX (these compounds may be prepared from the methods described in WO2020/079111), methyl (Z)-2-(5-cyclohexyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate + TX, methyl (Z)-2-(5-cyclopentyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoate + TX (these compounds may be prepared from the methods described in WO2020/193387), 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro- 2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile + TX, 4-[[6-[2-(2,4-difluorophenyl)-1,1- difluoro-2-hydroxy-3-(5-sulfanyl-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy] benzonitrile + TX, 4-[[6-[2-(2,4- difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3- pyridyl]oxy]benzonitrile + TX, trinexapac + TX, coumoxystrobin + TX, zhongshengmycin + TX, thiodiazole copper + TX, zinc thiazole + TX, amectotractin + TX, iprodione + TX, seboctylamine + TX; N'-[5-bromo-2-methyl-6-[(1S)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-[(1R)-1-methyl-2-propoxy-ethoxy]-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-chloro-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX, N'-[5-bromo-2-methyl-6-(1-methyl-2-propoxy-ethoxy)-3-pyridyl]-N-isopropyl-N-methyl-formamidine + TX (these compounds may be prepared from the methods described in WO2015/155075); N'-[5- bromo-2-methyl-6-(2-propoxypropoxy)-3-pyridyl]-N-ethyl-N-methyl-formamidine + TX (this compound may be prepared from the methods described in IPCOM000249876D); N-isopropyl-N’-[5-methoxy-2- methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenyl-ethyl)phenyl]-N-methyl-formamidine+ TX, N’-[4-(1- cyclopropyl-2,2,2-trifluoro-1-hydroxy-ethyl)-5-methoxy-2-methyl-phenyl]-N-isopropyl-N-methyl- formamidine + TX (these compounds may be prepared from the methods described in WO2018/228896); N-ethyl-N’-[5-methoxy-2-methyl-4-[(2-trifluoromethyl)oxetan-2-yl]phenyl]-N-methyl- formamidine + TX, N-ethyl-N’-[5-methoxy-2-methyl-4-[(2-trifuoromethyl)tetrahydrofuran-2-yl]phenyl]-N- methyl-formamidine + TX (these compounds may be prepared from the methods described in WO2019/110427); N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1R)-1- benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-3,3,3- trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide + TX, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]- 7,8-difluoro-quinoline-3-carboxamide + TX, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline- 3-carboxamide + TX, 8-fluoro-N-[(1R)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3- carboxamide + TX, 8-fluoro-N-[(1S)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3- carboxamide + TX, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N- [(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide + TX, N-((1R)-1-benzyl-3-chloro-1- methyl-but-3-enyl)-8-fluoro-quinoline-3-carboxamide + TX, N-((1S)-1-benzyl-3-chloro-1-methyl-but-3- enyl)-8-fluoro-quinoline-3-carboxamide + TX (these compounds may be prepared from the methods described in WO2017/153380); 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl- isoquinoline + TX, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline + TX, 4,4-difluoro-3,3-dimethyl-1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline + TX, 4,4-difluoro-3,3- dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline + TX, 1-(6-chloro-7-methyl-pyrazolo[1,5- a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline + TX (these compounds may be prepared from the methods described in WO2017/025510); 1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl- isoquinoline + TX, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline + TX, 6- chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline + TX, 4,4-difluoro-1-(5- fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline + TX, 3-(4,4-difluoro-3,3-dimethyl-1- isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole + TX (these compounds may be prepared from the methods described in WO2016/156085); N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]methyl]cyclopropanecarboxamide + TX, N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]methyl]propanamide + TX, N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]methyl]propanamide + TX, 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]methyl]urea + TX, 1,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]methyl]urea + TX, 3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3- yl]phenyl]methyl]urea + TX, N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide + TX, 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one + TX, 5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one + TX, ethyl 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrazole-4-carboxylate + TX, N,N-dimethyl- 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-1,2,4-triazol-3-amine + TX. The compounds in this paragraph may be prepared from the methods described in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689; 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3- pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol + TX (this compound may be prepared from the methods described in WO 2017/029179); 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1- yl)propan-2-ol + TX (this compound may be prepared from the methods described in WO 2017/029179); 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound may be prepared from the methods described in WO 2016/156290); 3-[2-(1- chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile + TX (this compound may be prepared from the methods described in WO 2016/156290); (4- phenoxyphenyl)methyl 2-amino-6-methyl-pyridine-3-carboxylate + TX (this compound may be prepared from the methods described in WO 2014/006945); 2,6-Dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6- c']dipyrrole-1,3,5,7(2H,6H)-tetrone + TX (this compound may be prepared from the methods described in WO 2011/138281); N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzenecarbothioamide + TX; N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX; (Z,2E)-5-[1-(2,4- dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide + TX (this compound may be prepared from the methods described in WO 2018/153707); N'-(2-chloro-5-methyl-4-phenoxy- phenyl)-N-ethyl-N-methyl-formamidine + TX; N'-[2-chloro-4-(2-fluorophenoxy)-5-methyl-phenyl]-N- ethyl-N-methyl-formamidine + TX (this compound may be prepared from the methods described in WO 2016/202742); 2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide + TX (this compound may be prepared from the methods described in WO 2014/095675); (5-methyl-2- pyridyl)-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone + TX, (3-methylisoxazol-5-yl)-[4- [5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methanone + TX (these compounds may be prepared from the methods described in WO 2017/220485); 2-oxo-N-propyl-2-[4-[5-(trifluoromethyl)-1,2,4- oxadiazol-3-yl]phenyl]acetamide + TX (this compound may be prepared from the methods described in WO 2018/065414); ethyl 1-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]pyrazole-4- carboxylate + TX (this compound may be prepared from the methods described in WO 2018/158365); 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide + TX, N-[(E)- methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX, N-[(Z)- methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX, N-[N-methoxy-C- methyl-carbonimidoyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide + TX (these compounds may be prepared from the methods described in WO 2018/202428); microbials including: Acinetobacter lwoffii + TX, Acremonium alternatum + TX + TX, Acremonium cephalosporium + TX + TX, Acremonium diospyri + TX, Acremonium obclavatum + TX, Adoxophyes orana granulovirus (AdoxGV) (Capex®) + TX, Agrobacterium radiobacter strain K84 (Galltrol-A®) + TX, Alternaria alternate + TX, Alternaria cassia + TX, Alternaria destruens (Smolder®) + TX, Ampelomyces quisqualis (AQ10®) + TX, Aspergillus flavus AF36 (AF36®) + TX, Aspergillus flavus NRRL 21882 (Aflaguard®) + TX, Aspergillus spp. + TX, Aureobasidium pullulans + TX, Azospirillum (MicroAZ®, TAZO B®) + TX, Azotobacter + TX, Azotobacter chroocuccum (Azotomeal®) + TX, Azotobacter cysts (Bionatural Blooming Blossoms®) + TX, Bacillus amyloliquefaciens + TX, Bacillus cereus + TX, Bacillus chitinosporus strain CM-1 + TX, Bacillus chitinosporus strain AQ746 + TX, Bacillus licheniformis strain HB-2 (e.g, Biostart™, formerly Rhizoboost®) + TX, Bacillus licheniformis strain 3086 (EcoGuard®, Green Releaf®) + TX, Bacillus circulans + TX, Bacillus firmus (BioSafe®, BioNem-WP®, VOTiVO®) + TX, Bacillus firmus strain I-1582 + TX, Bacillus macerans + TX, Bacillus marismortui + TX, Bacillus megaterium + TX, Bacillus mycoides strain AQ726 + TX, Bacillus papillae (Milky Spore Powder®) + TX, Bacillus pumilus spp. + TX, Bacillus pumilus strain GB34 (Yield Shield®) + TX, Bacillus pumilus strain AQ717 + TX, Bacillus pumilus strain QST 2808 (Sonata®, Ballad Plus®) + TX, Bacillus spahericus (VectoLex®) + TX, Bacillus spp. + TX, Bacillus spp. strain AQ175 + TX, Bacillus spp. strain AQ177 + TX, Bacillus spp. strain AQ178 + TX, Bacillus subtilis strain QST 713 (CEASE®, Serenade®, Rhapsody®) + TX, Bacillus subtilis strain QST 714 (JAZZ®) + TX, Bacillus subtilis strain AQ153 + TX, Bacillus subtilis strain AQ743 + TX, Bacillus subtilis strain QST3002 + TX, Bacillus subtilis strain QST3004 + TX, Bacillus subtilis var. amyloliquefaciens strain FZB24 (Taegro®, Rhizopro®) + TX, Bacillus thuringiensis Cry 2Ae + TX, Bacillus thuringiensis Cry1Ab + TX, Bacillus thuringiensis aizawai GC 91 (Agree®) + TX, Bacillus thuringiensis israelensis (BMP123®, Aquabac®, VectoBac®) + TX, Bacillus thuringiensis kurstaki (Javelin®, Deliver®, CryMax®, Bonide®, Scutella WP®, Turilav WP®, Astuto®, Dipel WP®, Biobit®, Foray®) + TX, Bacillus thuringiensis kurstaki BMP 123 (Baritone®) + TX, Bacillus thuringiensis kurstaki HD-1 (Bioprotec-CAF / 3P®) + TX, Bacillus thuringiensis strain BD#32 + TX, Bacillus thuringiensis strain AQ52 + TX, Bacillus thuringiensis var. aizawai (XenTari®, DiPel®) + TX, bacteria spp. (GROWMEND®, GROWSWEET®X, Shootup®) + TX, bacteriophage of Clavipacter michiganensis (AgriPhage®) + TX, Bakflor® + TX, Beauveria bassiana (Beaugenic®, Brocaril WP®) + TX, Beauveria bassiana GHA (Mycotrol ES®, Mycotrol O®, BotaniGuard®) + TX, Beauveria brongniartii (Engerlingspilz®, Schweizer Beauveria®, Melocont®) + TX, Beauveria spp. + TX, Botrytis cineria + TX, Bradyrhizobium japonicum (TerraMax®) + TX, Brevibacillus brevis + TX, Bacillus thuringiensis tenebrionis (Novodor®) + TX, BtBooster + TX, Burkholderia cepacia (Deny®, Intercept®, Blue Circle®) + TX, Burkholderia gladii + TX, Burkholderia gladioli + TX, Burkholderia spp. + TX, Canadian thistle fungus (CBH Canadian Bioherbicide®) + TX, Candida butyri + TX, Candida famata + TX, Candida fructus + TX, Candida glabrata + TX, Candida guilliermondii + TX, Candida melibiosica + TX, Candida oleophila strain O + TX, Candida parapsilosis + TX, Candida pelliculosa + TX, Candida pulcherrima + TX, Candida reukaufii + TX, Candida saitoana (Bio-Coat®, Biocure®) + TX, Candida sake + TX, Candida spp. + TX, Candida tenius + TX, Cedecea dravisae + TX, Cellulomonas flavigena + TX, Chaetomium cochliodes (Nova-Cide®) + TX, Chaetomium globosum (Nova-Cide®) + TX, Chromobacterium subtsugae strain PRAA4-1T (Grandevo®) + TX, Cladosporium cladosporioides + TX, Cladosporium oxysporum + TX, Cladosporium chlorocephalum + TX, Cladosporium spp. + TX, Cladosporium tenuissimum + TX, Clonostachys rosea (EndoFine®) + TX, Colletotrichum acutatum + TX, Coniothyrium minitans (Cotans WG®) + TX, Coniothyrium spp. + TX, Cryptococcus albidus (YIELDPLUS®) + TX, Cryptococcus humicola + TX, Cryptococcus infirmo-miniatus + TX, Cryptococcus laurentii + TX, Cryptophlebia leucotreta granulovirus (Cryptex®) + TX, Cupriavidus campinensis + TX, Cydia pomonella granulovirus (CYD-X®) + TX, Cydia pomonella granulovirus (Madex®, Madex® Plus, Madex® Max, Carpovirusine Evo2®) + TX, Cylindrobasidium laeve (Stumpout®) + TX, Cylindrocladium + TX, Debaryomyces hansenii + TX, Drechslera hawaiinensis + TX, Enterobacter cloacae + TX, Enterobacteriaceae + TX, Entomophtora virulenta (Vektor®) + TX, Epicoccum nigrum + TX, Epicoccum purpurascens + TX, Epicoccum spp. + TX, Filobasidium floriforme + TX, Fusarium acuminatum + TX, Fusarium chlamydosporum + TX, Fusarium oxysporum (Fusaclean®, Biofox C®) + TX, Fusarium proliferatum + TX, Fusarium spp. + TX, Galactomyces geotrichum + TX, Gliocladium catenulatum (Primastop®, Prestop®) + TX, Gliocladium roseum + TX, Gliocladium spp. (SoilGard®) + TX, Gliocladium virens (Soilgard®) + TX, Granulovirus (Granupom®) + TX, Halobacillus halophilus + TX, Halobacillus litoralis + TX, Halobacillus trueperi + TX, Halomonas spp. + TX, Halomonas subglaciescola + TX, Halovibrio variabilis + TX, Hanseniaspora uvarum + TX, Helicoverpa armigera nucleopolyhedrovirus (Helicovex®) + TX, Helicoverpa zea nuclear polyhedrosis virus (Gemstar®) + TX, Isoflavone – formononetin (Myconate®) + TX, Kloeckera apiculata + TX, Kloeckera spp. + TX, Lagenidium giganteum (Laginex®) + TX, Lecanicillium longisporum (Vertiblast®) + TX, Lecanicillium muscarium (Vertikil®) + TX, Lymantria Dispar nucleopolyhedrosis virus (Disparvirus®) + TX, Marinococcus halophilus + TX, Meira geulakonigii + TX, Metarhizium anisopliae (Met52®) + TX, Metarhizium anisopliae (Destruxin WP®) + TX, Metschnikowia fruticola (Shemer®) + TX, Metschnikowia pulcherrima + TX, Microdochium dimerum (Antibot®) + TX, Micromonospora coerulea + TX, Microsphaeropsis ochracea + TX, Muscodor albus 620 (Muscudor®) + TX, Muscodor roseus strain A3- 5 + TX, Mycorrhizae spp. (AMykor®, Root Maximizer®) + TX, Myrothecium verrucaria strain AARC- 0255 (DiTera®) + TX, BROS PLUS® + TX, Ophiostoma piliferum strain D97 (Sylvanex®) + TX, Paecilomyces farinosus + TX, Paecilomyces fumosoroseus (PFR-97®, PreFeRal®) + TX, Paecilomyces linacinus (Biostat WP®) + TX, Paecilomyces lilacinus strain 251 (MeloCon WG®) + TX, Paenibacillus polymyxa + TX, Pantoea agglomerans (BlightBan C9-1®) + TX, Pantoea spp. + TX, Pasteuria spp. (Econem®) + TX, Pasteuria nishizawae + TX, Penicillium aurantiogriseum + TX, Penicillium billai (Jumpstart®, TagTeam®) + TX, Penicillium brevicompactum + TX, Penicillium frequentans + TX, Penicillium griseofulvum + TX, Penicillium purpurogenum + TX, Penicillium spp. + TX, Penicillium viridicatum + TX, Phlebiopsis gigantean (Rotstop®) + TX, phosphate solubilizing bacteria (Phosphomeal®) + TX, Phytophthora cryptogea + TX, Phytophthora palmivora (Devine®) + TX, Pichia anomala + TX, Pichia guilermondii + TX, Pichia membranaefaciens + TX, Pichia onychis + TX, Pichia stipites + TX, Pseudomonas aeruginosa + TX, Pseudomonas aureofasciens (Spot-Less Biofungicide®) + TX, Pseudomonas cepacia + TX, Pseudomonas chlororaphis (AtEze®) + TX, Pseudomonas corrugate + TX, Pseudomonas fluorescens strain A506 (BlightBan A506®) + TX, Pseudomonas putida + TX, Pseudomonas reactans + TX, Pseudomonas spp. + TX, Pseudomonas syringae (Bio-Save®) + TX, Pseudomonas viridiflava + TX, Pseudomons fluorescens (Zequanox®) + TX, Pseudozyma flocculosa strain PF-A22 UL (Sporodex L®) + TX, Puccinia canaliculata + TX, Puccinia thlaspeos (Wood Warrior®) + TX, Pythium paroecandrum + TX, Pythium oligandrum (Polygandron®, Polyversum®) + TX, Pythium periplocum + TX, Rhanella aquatilis + TX, Rhanella spp. + TX, Rhizobia (Dormal®, Vault®) + TX, Rhizoctonia + TX, Rhodococcus globerulus strain AQ719 + TX, Rhodosporidium diobovatum + TX, Rhodosporidium toruloides + TX, Rhodotorula spp. + TX, Rhodotorula glutinis + TX, Rhodotorula graminis + TX, Rhodotorula mucilagnosa + TX, Rhodotorula rubra + TX, Saccharomyces cerevisiae + TX, Salinococcus roseus + TX, Sclerotinia minor + TX, Sclerotinia minor (SARRITOR®) + TX, Scytalidium spp. + TX, Scytalidium uredinicola + TX, Spodoptera exigua nuclear polyhedrosis virus (Spod-X®, Spexit®) + TX, Serratia marcescens + TX, Serratia plymuthica + TX, Serratia spp. + TX, Sordaria fimicola + TX, Spodoptera littoralis nucleopolyhedrovirus (Littovir®) + TX, Sporobolomyces roseus + TX, Stenotrophomonas maltophilia + TX, Streptomyces ahygroscopicus + TX, Streptomyces albaduncus + TX, Streptomyces exfoliates + TX, Streptomyces galbus + TX, Streptomyces griseoplanus + TX, Streptomyces griseoviridis (Mycostop®) + TX, Streptomyces lydicus (Actinovate®) + TX, Streptomyces lydicus WYEC-108 (ActinoGrow®) + TX, Streptomyces violaceus + TX, Tilletiopsis minor + TX, Tilletiopsis spp. + TX, Trichoderma asperellum (T34 Biocontrol®) + TX, Trichoderma gamsii (Tenet®) + TX, Trichoderma atroviride (Plantmate®) + TX, Trichoderma hamatum TH 382 + TX, Trichoderma harzianum rifai (Mycostar®) + TX, Trichoderma harzianum T-22 (Trianum-P®, PlantShield HC®, RootShield®, Trianum-G®) + TX, Trichoderma harzianum T-39 (Trichodex®) + TX, Trichoderma inhamatum + TX, Trichoderma koningii + TX, Trichoderma spp. LC 52 (Sentinel®) + TX, Trichoderma lignorum + TX, Trichoderma longibrachiatum + TX, Trichoderma polysporum (Binab T®) + TX, Trichoderma taxi + TX, Trichoderma virens + TX, Trichoderma virens (formerly Gliocladium virens GL- 21) (SoilGuard®) + TX, Trichoderma viride + TX, Trichoderma viride strain ICC 080 (Remedier®) + TX, Trichosporon pullulans + TX, Trichosporon spp. + TX, Trichothecium spp. + TX, Trichothecium roseum + TX, Typhula phacorrhiza strain 94670 + TX, Typhula phacorrhiza strain 94671 + TX, Ulocladium atrum + TX, Ulocladium oudemansii (Botry-Zen®) + TX, Ustilago maydis + TX, various bacteria and supplementary micronutrients (Natural II®) + TX, various fungi (Millennium Microbes®) + TX, Verticillium chlamydosporium + TX, Verticillium lecanii (Mycotal®, Vertalec®) + TX, Vip3Aa20 (VIPtera®) + TX, Virgibaclillus marismortui + TX, Xanthomonas campestris pv. Poae (Camperico®) + TX, Xenorhabdus bovienii + TX, and Xenorhabdus nematophilus + TX; Plant extracts including: pine oil (Retenol®) + TX, azadirachtin (Plasma Neem Oil®, AzaGuard®, MeemAzal®, Molt-X®) + TX, Botanical IGR (Neemazad®, Neemix®) + TX, canola oil (Lilly Miller Vegol®) + TX, Chenopodium ambrosioides near ambrosioides (Requiem®) + TX, Chrysanthemum extract (Crisant®) + TX, extract of neem oil (Trilogy®) + TX, essentials oils of Labiatae (Botania®) + TX, extracts of clove rosemary peppermint and thyme oil (Garden insect killer®) + TX, Glycinebetaine (Greenstim®) + TX, garlic + TX, lemongrass oil (GreenMatch®) + TX, neem oil + TX, Nepeta cataria (Catnip oil) + TX, Nepeta catarina + TX, nicotine + TX, oregano oil (MossBuster®) + TX, Pedaliaceae oil (Nematon®) + TX, pyrethrum + TX, Quillaja saponaria (NemaQ®) + TX, Reynoutria ® (Regalia®, Sakalia®) + TX, rotenone (Eco Roten®) + TX, Rutaceae plant extract (Soleo®) + TX, soybean oil (Ortho ecosense®) + TX, Melaleuca alternifolia extract (also called tea tree oil) (Timorex Gold®) + TX, thymus oil + TX, AGNIQUE® MMF + TX, BugOil® + TX, mixture of rosemary sesame pepermint thyme and cinnamon extracts (EF 300®) + TX, mixture of clove rosemary and peppermint extract (EF 400®) + TX, mixture of clove pepermint garlic oil and mint (Soil Shot®) + TX, kaolin (Screen®) + TX, storage glucam of brown algae (Laminarin®) +TX; pheromones including: blackheaded fireworm pheromone (3M Sprayable Blackheaded Fireworm Pheromone®) + TX, Codling Moth Pheromone (Paramount dispenser-(CM)/ Isomate C-Plus®) + TX, Grape Berry Moth Pheromone (3M MEC-GBM Sprayable Pheromone®) + TX, Leafroller pheromone (3M MEC – LR Sprayable Pheromone®) + TX, Muscamone (Snip7 Fly Bait®, Starbar Premium Fly Bait®) + TX, Oriental Fruit Moth Pheromone (3M oriental fruit moth sprayable pheromone®) + TX, Peachtree Borer Pheromone (Isomate-P®) + TX, Tomato Pinworm Pheromone (3M Sprayable pheromone®) + TX, Entostat powder (extract from palm tree) (Exosex CM®) + TX, (3E,8Z,11Z)-3,8,11- Tetradecatrienyl acetate + TX, (7Z,11Z,13E)-7,11,13-Hexadecatrienal + TX, (E,Z)-7,9-Dodecadien-1-yl acetate + TX, 2-Methyl-1-butanol + TX, Calcium acetate + TX, Scenturion® + TX, Biolure® + TX, Check- Mate® + TX, Lavandulyl senecioate + TX; Macrobials including: Aphelinus abdominalis + TX, Aphidius ervi (Aphelinus-System®) + TX, Acerophagus papaya + TX, Adalia bipunctata (Adalia-System®) + TX, Adalia bipunctata (Adaline®) + TX, Adalia bipunctata (Aphidalia®) + TX, Ageniaspis citricola + TX, Ageniaspis fuscicollis + TX, Amblyseius andersoni (Anderline®, Andersoni-System®) + TX, Amblyseius californicus (Amblyline®, Spical®) + TX, Amblyseius cucumeris (Thripex®, Bugline cucumeris®) + TX, Amblyseius fallacis (Fallacis®) + TX, Amblyseius swirskii (Bugline swirskii®, Swirskii-Mite®) + TX, Amblyseius womersleyi (WomerMite®) + TX, Amitus hesperidum + TX, Anagrus atomus + TX, Anagyrus fusciventris + TX, Anagyrus kamali + TX, Anagyrus loecki + TX, Anagyrus pseudococci (Citripar®) + TX, Anicetus benefices + TX, Anisopteromalus calandrae + TX, Anthocoris nemoralis (Anthocoris-System®) + TX, Aphelinus abdominalis (Apheline®, Aphiline®) + TX, Aphelinus asychis + TX, Aphidius colemani (Aphipar®) + TX, Aphidius ervi (Ervipar®) + TX, Aphidius gifuensis + TX, Aphidius matricariae (Aphipar- M®) + TX, Aphidoletes aphidimyza (Aphidend®) + TX, Aphidoletes aphidimyza (Aphidoline®) + TX, Aphytis lingnanensis + TX, Aphytis melinus + TX, Aprostocetus hagenowii + TX, Atheta coriaria (Staphyline®) + TX, Bombus spp. + TX, Bombus terrestris (Natupol Beehive®) + TX, Bombus terrestris (Beeline®, Tripol®) + TX, Cephalonomia stephanoderis + TX, Chilocorus nigritus + TX, Chrysoperla carnea (Chrysoline®) + TX, Chrysoperla carnea (Chrysopa®) + TX, Chrysoperla rufilabris + TX, Cirrospilus ingenuus + TX, Cirrospilus quadristriatus + TX, Citrostichus phyllocnistoides + TX, Closterocerus chamaeleon + TX, Closterocerus spp. + TX, Coccidoxenoides perminutus (Planopar®) + TX, Coccophagus cowperi + TX, Coccophagus lycimnia + TX, Cotesia flavipes + TX, Cotesia plutellae + TX, Cryptolaemus montrouzieri (Cryptobug®, Cryptoline®) + TX, Cybocephalus nipponicus + TX, Dacnusa sibirica + TX, Dacnusa sibirica (Minusa®) + TX, Diglyphus isaea (Diminex®) + TX, Delphastus catalinae (Delphastus®) + TX, Delphastus pusillus + TX, Diachasmimorpha krausii + TX, Diachasmimorpha longicaudata + TX, Diaparsis jucunda + TX, Diaphorencyrtus aligarhensis + TX, Diglyphus isaea + TX, Diglyphus isaea (Miglyphus®, Digline®) + TX, Dacnusa sibirica (DacDigline®, Minex®) + TX, Diversinervus spp. + TX, Encarsia citrina + TX, Encarsia formosa (Encarsia max®, Encarline®, En-Strip®) + TX, Eretmocerus eremicus (Enermix®) + TX, Encarsia guadeloupae + TX, Encarsia haitiensis + TX, Episyrphus balteatus (Syrphidend®) + TX, Eretmoceris siphonini + TX, Eretmocerus californicus + TX, Eretmocerus eremicus (Ercal®, Eretline e®) + TX, Eretmocerus eremicus (Bemimix®) + TX, Eretmocerus hayati + TX, Eretmocerus mundus (Bemipar®, Eretline m®) + TX, Eretmocerus siphonini + TX, Exochomus quadripustulatus + TX, Feltiella acarisuga (Spidend®) + TX, Feltiella acarisuga (Feltiline®) + TX, Fopius arisanus + TX, Fopius ceratitivorus + TX, Formononetin (Wirless Beehome®) + TX, Franklinothrips vespiformis (Vespop®) + TX, Galendromus occidentalis + TX, Goniozus legneri + TX, Habrobracon hebetor + TX, Harmonia axyridis (HarmoBeetle®) + TX, Heterorhabditis spp. (Lawn Patrol®) + TX, Heterorhabditis bacteriophora (NemaShield HB®, Nemaseek®, Terranem-Nam®, Terranem®, Larvanem®, B-Green®, NemAttack®, Nematop®) + TX, Heterorhabditis megidis (Nemasys H®, BioNem H®, Exhibitline hm®, Larvanem-M®) + TX, Hippodamia convergens + TX, Hypoaspis aculeifer (Aculeifer-System®, Entomite-A®) + TX, Hypoaspis miles (Hypoline m®, Entomite-M®) + TX, Lbalia leucospoides + TX, Lecanoideus floccissimus + TX, Lemophagus errabundus + TX, Leptomastidea abnormis + TX, Leptomastix dactylopii (Leptopar®) + TX, Leptomastix epona + TX, Lindorus lophanthae + TX, Lipolexis oregmae + TX, Lucilia caesar (Natufly®) + TX, Lysiphlebus testaceipes + TX, Macrolophus caliginosus (Mirical-N®, Macroline c®, Mirical®) + TX, Mesoseiulus longipes + TX, Metaphycus flavus + TX, Metaphycus lounsburyi + TX, Micromus angulatus (Milacewing®) + TX, Microterys flavus + TX, Muscidifurax raptorellus and Spalangia cameroni (Biopar®) + TX, Neodryinus typhlocybae + TX, Neoseiulus californicus + TX, Neoseiulus cucumeris (THRYPEX®) + TX, Neoseiulus fallacis + TX, Nesideocoris tenuis (NesidioBug®, Nesibug®) + TX, Ophyra aenescens (Biofly®) + TX, Orius insidiosus (Thripor-I®, Oriline i®) + TX, Orius laevigatus (Thripor-L®, Oriline l®) + TX, Orius majusculus (Oriline m®) + TX, Orius strigicollis (Thripor- S®) + TX, Pauesia juniperorum + TX, Pediobius foveolatus + TX, Phasmarhabditis hermaphrodita (Nemaslug®) + TX, Phymastichus coffea + TX, Phytoseiulus macropilus + TX, Phytoseiulus persimilis (Spidex®, Phytoline p®) + TX, Podisus maculiventris (Podisus®) + TX, Pseudacteon curvatus + TX, Pseudacteon obtusus + TX, Pseudacteon tricuspis + TX, Pseudaphycus maculipennis + TX, Pseudleptomastix mexicana + TX, Psyllaephagus pilosus + TX, Psyttalia concolor (complex) + TX, Quadrastichus spp. + TX, Rhyzobius lophanthae + TX, Rodolia cardinalis + TX, Rumina decollate + TX, Semielacher petiolatus + TX, Sitobion avenae (Ervibank®) + TX, Steinernema carpocapsae (Nematac C®, Millenium®, BioNem C®, NemAttack®, Nemastar®, Capsanem®) + TX, Steinernema feltiae (NemaShield®, Nemasys F®, BioNem F, Steinernema-System®, NemAttack®, Nemaplus®, Exhibitline sf®, Scia-rid®, Entonem®) + TX, Steinernema kraussei (Nemasys L®, BioNem L®, Exhibitline srb®) + TX, Steinernema riobrave (BioVector®, BioVektor®) + TX, Steinernema scapterisci (Nematac S®) + TX, Steinernema spp. + TX, Steinernematid spp. (Guardian Nematodes®) + TX, Stethorus punctillum (Stethorus®) + TX, Tamarixia radiate + TX, Tetrastichus setifer + TX, Thripobius semiluteus + TX, Torymus sinensis + TX, Trichogramma brassicae (Tricholine b®) + TX, Trichogramma brassicae (Tricho-Strip®) + TX, Trichogramma evanescens + TX, Trichogramma minutum + TX, Trichogramma ostriniae + TX, Trichogramma platneri + TX, Trichogramma pretiosum + TX, Xanthopimpla stemmator + TX; other biologicals including: abscisic acid + TX, bioSea® + TX, Chondrostereum purpureum (Chontrol Paste®) + TX, Colletotrichum gloeosporioides (Collego®) + TX, Copper Octanoate (Cueva®) + TX, Delta traps (Trapline d®) + TX, Erwinia amylovora (Harpin) (ProAct®, Ni-HIBIT Gold CST®) + TX, fatty acids derived from a natural by-product of extra virgin olive oil (FLIPPER®), Ferri-phosphate (Ferramol®) + TX, Funnel traps (Trapline y®) + TX, Gallex® + TX, Grower's Secret® + TX, Homo- brassonolide + TX, Iron Phosphate (Lilly Miller Worry Free Ferramol Slug & Snail Bait®) + TX, MCP hail trap (Trapline f®) + TX, Microctonus hyperodae + TX, Mycoleptodiscus terrestris (Des-X®) + TX, BioGain® + TX, Aminomite® + TX, Zenox® + TX, Pheromone trap (Thripline ams®) + TX, potassium bicarbonate (MilStop®) + TX, potassium salts of fatty acids (Sanova®) + TX, potassium silicate solution (Sil-Matrix®) + TX, potassium iodide + potassiumthiocyanate (Enzicur®) + TX, SuffOil-X® + TX, Spider venom + TX, Nosema locustae (Semaspore Organic Grasshopper Control®) + TX, Sticky traps (Trapline YF®, Rebell Amarillo®) + TX and Traps (Takitrapline y + b®) + TX; (1) antibacterial agents selected from the group of: (1.1) bacteria, examples of which are Bacillus mojavensis strain R3B (Accession No. NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC + TX; Bacillus pumilus, in particular strain BU F-33, having NRRL Accession No.50185 (CARTISSA® from BASF, EPA Reg. No.71840-19) + TX; Bacillus subtilis, in particular strain QST713/AQ713 (SERENADE OPTI or SERENADE ASO from Bayer CropScience LP, US, having NRRL Accession No. B21661, U.S. Patent No.6,060,051) + TX; Bacillus subtilis strain BU1814, (VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX; Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No.70127-5)) + TX; Bacillus subtilis CX-9060 from Certis USA LLC + TX; Bacillus sp., in particular strain D747 (available as DOUBLE NICKEL® from Kumiai Chemical Industry Co., Ltd.), having Accession No. FERM BP-8234, U.S. Patent No. 7,094,592 + TX; Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297 + TX; Paenibacillus polymyxa, in particular strain AC- 1 (e.g. TOPSEED® from Green Biotech Company Ltd.) + TX; Pantoea agglomerans, in particular strain E325 (Accession No. NRRL B-21856) (available as BLOOMTIME BIOLOGICAL™ FD BIOPESTICIDE from Northwest Agri Products) + TX; Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX; and (1.2) fungi, examples of which are Aureobasidium pullulans, in particular blastospores of strain DSM14940, blastospores of strain DSM 14941 or mixtures of blastospores of strains DSM14940 and DSM14941 (e.g., BOTECTOR® and BLOSSOM PROTECT® from bio-ferm, CH) + TX; Pseudozyma aphidis (as disclosed in WO2011/151819 by Yissum Research Development Company of the Hebrew University of Jerusalem) + TX; Saccharomyces cerevisiae, in particular strains CNCM No. 1-3936, CNCM No.1-3937, CNCM No.1-3938 or CNCM No.1-3939 (as disclosed in WO 2010/086790 from Lesaffre et Compagnie, FR) + TX; (2) biological fungicides selected from the group of: (2.1) bacteria, examples of which are Agrobacterium radiobacter strain K84 (e.g. GALLTROL-A® from AgBioChem, CA) + TX; Agrobacterium radiobacter strain K1026 (e.g. NOGALL™ from BASF SE) + TX; Bacillus subtilis var. amyloliquefaciens strain FZB24 having Accession No. DSM 10271 (available from Novozymes as TAEGRO® or TAEGRO® ECO (EPA Registration No. 70127-5)) + TX; Bacillus amyloliquefaciens, in particular strain D747 (available as Double Nickel™ from Kumiai Chemical Industry Co., Ltd., having accession number FERM BP-8234, US Patent No.7,094,592) + TX; Bacillus amyloliquefaciens strain F727 (also known as strain MBI110) (NRRL Accession No. B-50768, WO 2014/028521) (STARGUS® from Marrone Bio Innovations) + TX; Bacillus amyloliquefaciens strain FZB42, Accession No. DSM 23117 (available as RHIZOVITAL® from ABiTEP, DE) + TX; Bacillus amyloliquefaciens isolate B246 (e.g. AVOGREEN™ from University of Pretoria) + TX; Bacillus licheniformis, in particular strain SB3086, having Accession No. ATCC 55406, WO 2003/000051 (available as ECOGUARD® Biofungicide and GREEN RELEAF™ from Novozymes) + TX; Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (QUARTZO® (WG) and PRESENCE® (WP) from FMC Corporation) + TX; Bacillus methylotrophicus strain BAC-9912 (from Chinese Academy of Sciences’ Institute of Applied Ecology) + TX; Bacillus mojavensis strain R3B (Accession No. NCAIM (P) B001389) (WO 2013/034938) from Certis USA LLC + TX; Bacillus mycoides, isolate, having Accession No. B-30890 (available as BMJ TGAI® or WG and LifeGard™ from Certis USA LLC) + TX; Bacillus pumilus, in particular strain QST2808 (available as SONATA® from Bayer CropScience LP, US, having Accession No. NRRL B-30087 and described in U.S. Patent No.6,245,551) + TX; Bacillus pumilus, in particular strain GB34 (available as Yield Shield® from Bayer AG, DE) + TX; Bacillus pumilus, in particular strain BU F-33, having NRRL Accession No. 50185 (available as part of the CARTISSA product from BASF, EPA Reg. No.71840-19) + TX; Bacillus subtilis, in particular strain QST713/AQ713 (available as SERENADE OPTI or SERENADE ASO from Bayer CropScience LP, US, having NRRL Accession No. B21661 and described in U.S. Patent No. 6,060,051) + TX; Bacillus subtilis Y1336 (available as BIOBAC® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos.4764, 5454, 5096 and 5277) + TX; Bacillus subtilis strain MBI 600 (available as SUBTILEX from BASF SE), having Accession Number NRRL B-50595, U.S. Patent No.5,061,495 + TX; Bacillus subtilis strain GB03 (available as Kodiak® from Bayer AG, DE) + TX; Bacillus subtilis strain BU1814, (available as VELONDIS® PLUS, VELONDIS® FLEX and VELONDIS® EXTRA from BASF SE) + TX; Bacillus subtilis CX-9060 from Certis USA LLC + TX; Bacillus subtilis KTSB strain (FOLIACTIVE® from Donaghys) + TX; Bacillus subtilis IAB/BS03 (AVIV™ from STK Bio-Ag Technologies, PORTENTO® from Idai Nature) + TX; Bacillus subtilis strain Y1336 (available as BIOBAC® WP from Bion-Tech, Taiwan, registered as a biological fungicide in Taiwan under Registration Nos.4764, 5454, 5096 and 5277) + TX; Paenibacillus epiphyticus (WO 2016/020371) from BASF SE + TX; Paenibacillus polymyxa ssp. plantarum (WO 2016/020371) from BASF SE + TX; Paenibacillus sp. strain having Accession No. NRRL B-50972 or Accession No. NRRL B-67129, WO 2016/154297 + TX; Pseudomonas chlororaphis strain AFS009, having Accession No. NRRL B-50897, WO 2017/019448 (e.g., HOWLER™ and ZIO® from AgBiome Innovations, US) + TX; Pseudomonas chlororaphis, in particular strain MA342 (e.g. CEDOMON®, CERALL®, and CEDRESS® by Bioagri and Koppert) + TX; Pseudomonas fluorescens strain A506 (e.g. BLIGHTBAN® A506 by NuFarm) + TX; Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX; Streptomyces griseoviridis strain K61 (also known as Streptomyces galbus strain K61) (Accession No. DSM 7206) (MYCOSTOP® from Verdera, PREFENCE® from BioWorks, cf. Crop Protection 2006, 25, 468-475) + TX; Streptomyces lydicus strain WYEC108 (also known as Streptomyces lydicus strain WYCD108US) (ACTINO-IRON® and ACTINOVATE® from Novozymes) + TX; and (2.2) fungi, examples of which are Ampelomyces quisqualis, in particular strain AQ 10 (e.g. AQ 10® by IntrachemBio Italia) + TX; Ampelomyces quisqualis strain AQ10, having Accession No. CNCM 1-807 (e.g., AQ 10® by IntrachemBio Italia) + TX; Aspergillus flavus strain NRRL 21882 (products known as AFLA-GUARD® from Syngenta/ChemChina) + TX; Aureobasidium pullulans, in particular blastospores of strain DSM14940 + TX; Aureobasidium pullulans, in particular blastospores of strain DSM 14941 + TX; Aureobasidium pullulans, in particular mixtures of blastospores of strains DSM14940 and DSM 14941 (e.g. Botector® by bio-ferm, CH) + TX; Chaetomium cupreum (Accession No. CABI 353812) (e.g. BIOKUPRUM™ by AgriLife) + TX; Chaetomium globosum (available as RIVADIOM® by Rivale) + TX; Cladosporium cladosporioides, strain H39, having Accession No. CBS122244, US 2010/0291039 (by Stichting Dienst Landbouwkundig Onderzoek) + TX; Coniothyrium minitans, in particular strain CON/M/91-8 (Accession No. DSM9660, e.g. Contans ® from Bayer CropScience Biologics GmbH) + TX; Cryptococcus flavescens, strain 3C (NRRL Y-50378), (B2.2.99) + TX; Dactylaria candida + TX; Dilophosphora alopecuri (available as TWIST FUNGUS®) + TX; Fusarium oxysporum, strain Fo47 (available as FUSACLEAN® by Natural Plant Protection) + TX; Gliocladium catenulatum (Synonym: Clonostachys rosea f. catenulate) strain J1446 (e.g. Prestop ® by Lallemand) + TX; Gliocladium roseum (also known as Clonostachys rosea f rosea), in particular strain 321U from Adjuvants Plus, strain ACM941 as disclosed in Xue A.G (Efficacy of Clonostachys rosea strain ACM941 and fungicide seed treatments for controlling the root tot complex of field pea, Can. J. Plant Sci.2003, 83(3): 519-524), or strain IK726 (Jensen DF, et al. Development of a biocontrol agent for plant disease control with special emphasis on the near commercial fungal antagonist Clonostachys rosea strain ’IK726’, Australasian Plant Pathol. 2007,36(2), 95-101) + TX; Lecanicillium lecanii (formerly known as Verticillium lecanii) conidia of strain KV01 (e.g. Vertalec® by Koppert/Arysta) + TX; Metschnikowia fructicola, in particular strain NRRL Y-30752, (B2.2.3) + TX; Microsphaeropsis ochracea + TX; Muscodor roseus, in particular strain A3-5 (Accession No. NRRL 30548) + TX; Penicillium steckii (DSM 27859, WO 2015/067800) from BASF SE + TX; Penicillium vermiculatum + TX; Phlebiopsis gigantea strain VRA 1992 (ROTSTOP® C from Danstar Ferment) + TX; Pichia anomala, strain WRL-076 (NRRL Y-30842), U.S. Patent No. 7,579,183 + TX; Pseudozyma flocculosa, strain PF-A22 UL (available as SPORODEX® L by Plant Products Co., CA) + TX; Saccharomyces cerevisiae, in particular strain LASO2 (from Agro-Levures et Dérivés), strain LAS117 cell walls (CEREVISANE® from Lesaffre, ROMEO® from BASF SE), strains CNCM No.1-3936, CNCM No.1-3937, CNCM No.1-3938, CNCM No.1-3939 (WO 2010/086790) from Lesaffre et Compagnie, FR + TX; Simplicillium lanosoniveum + TX; Talaromyces flavus, strain V117b + TX; Trichoderma asperelloides JM41R (Accession No. NRRL B-50759) (TRICHO PLUS® from BASF SE) + TX; Trichoderma asperellum, in particular, strain kd (e.g. T-Gro from Andermatt Biocontrol) + TX; Trichoderma asperellum, in particular strain SKT-1, having Accession No. FERM P-16510 (e.g. ECO- HOPE® from Kumiai Chemical Industry), strain T34 (e.g. T34 Biocontrol by Biocontrol Technologies S.L., ES) or strain ICC 012 from Isagro + TX; Trichoderma atroviride, in particular strain SC1 (Accession No. CBS 122089, WO 2009/116106 and U.S. Patent No.8,431,120 (from Bi-PA)), strain 77B (T77 from Andermatt Biocontrol) or strain LU132 (e.g. Sentinel from Agrimm Technologies Limited) + TX; Trichoderma atroviride, strain CNCM 1-1237 (e.g. Esquive® WP from Agrauxine, FR) + TX; Trichoderma atroviride, strain no. V08/002387 + TX; Trichoderma atroviride, strain NMI no. V08/002388 + TX; Trichoderma atroviride, strain NMI no. V08/002389 + TX; Trichoderma atroviride, strain NMI no. V08/002390 + TX; Trichoderma atroviride, strain LC52 (e.g. Tenet by Agrimm Technologies Limited) + TX; Trichoderma atroviride, strain ATCC 20476 (IMI 206040) + TX; Trichoderma atroviride, strain T11 (IMI352941/ CECT20498) + TX; Trichoderma atroviride, strain SKT-1 (FERM P-16510), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma atroviride, strain SKT-2 (FERM P-16511), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma atroviride, strain SKT-3 (FERM P-17021), JP Patent Publication (Kokai) 11-253151 A + TX; Trichoderma fertile (e.g. product TrichoPlus from BASF) + TX; Trichoderma gamsii (formerly T. viride), strain ICC080 (IMI CC 392151 CABI, e.g. BioDerma by AGROBIOSOL DE MEXICO, S.A. DE C.V.) + TX; Trichoderma gamsii (formerly T. viride), strain ICC 080 (IMI CC 392151 CABI) (available as BIODERMA® by AGROBIOSOL DE MEXICO, S.A. DE C.V.) + TX; Trichoderma harmatum + TX; Trichoderma harmatum, having Accession No. ATCC 28012 + TX; Trichoderma harzianum strain T-22 (e.g. Trianum-P from Andermatt Biocontrol or Koppert) or strain Cepa SimbT5 (from Simbiose Agro) + TX; Trichoderma harzianum + TX; Trichoderma harzianum rifai T39 (e.g. Trichodex® from Makhteshim, US) + TX; Trichoderma harzianum, strain ITEM 908 (e.g. Trianum-P from Koppert) + TX; Trichoderma harzianum, strain TH35 (e.g. Root-Pro by Mycontrol) + TX; Trichoderma harzianum, strain DB 103 (available as T-GRO® 7456 by Dagutat Biolab) + TX; Trichoderma polysporum, strain IMI 206039 (e.g. Binab TF WP by BINAB Bio-Innovation AB, Sweden) + TX; Trichoderma stromaticum, having Accession No. Ts3550 (e.g. Tricovab by CEPLAC, Brazil) + TX; Trichoderma virens (also known as Gliocladium virens), in particular strain GL-21 (e.g. SoilGard by Certis, US) + TX; Trichoderma virens strain G-41, formerly known as Gliocladium virens (Accession No. ATCC 20906) (e.g., ROOTSHIELD® PLUS WP and TURFSHIELD® PLUS WP from BioWorks, US) + TX; Trichoderma viride, strain TV1(e.g. Trianum-P by Koppert) + TX; Trichoderma viride, in particular strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161: 125-137) + TX; mixtures of Trichoderma asperellum strain ICC 012 (also known as Trichoderma harzianum ICC012), having Accession No. CABI CC IMI 392716 and Trichoderma gamsii (formerly T. viride) strain ICC 080, having Accession No. IMI 392151 (e.g., BIO-TAM™ from Isagro USA, Inc. or BIODERMA® by Agrobiosol de Mexico, S.A. de C.V.) + TX; Ulocladium oudemansii strain U3, having Accession No. NM 99/06216 (e.g., BOTRY-ZEN® by Botry-Zen Ltd, New Zealand and BOTRYSTOP® from BioWorks, Inc.) + TX; Verticillium albo-atrum (formerly V. dahliae), strain WCS850 having Accession No. WCS850, deposited at the Central Bureau for Fungi Cultures (e.g., DUTCH TRIG® by Tree Care Innovations) + TX; Verticillium chlamydosporium + TX; (3) biological control agents having an effect for improving plant growth and/or plant health selected from the group of: (3.1) bacteria, examples of which are Azospirillum brasilense (e.g., VIGOR® from KALO, Inc.) + TX; Azospirillum lipoferum (e.g., VERTEX-IF™ from TerraMax, Inc.) + TX; Azorhizobium caulinodans, in particular strain ZB-SK-5 + TX; Azotobacter chroococcum, in particular strain H23 + TX; Azotobacter vinelandii, in particular strain ATCC 12837 + TX; a mixture of Azotobacter vinelandii and Clostridium pasteurianum (available as INVIGORATE® from Agrinos) + TX; Bacillus amyloliquefaciens pm414 (LOLI-PEPTA® from Biofilm Crop Protection) + TX; Bacillus amyloliquefaciens SB3281 (ATCC # PTA- 7542, WO 2017/205258) + TX; Bacillus amyloliquefaciens TJ1000 (available as QUIKROOTS® from Novozymes) + TX; Bacillus amyloliquefaciens, in particular strain IN937a + TX; Bacillus amyloliquefaciens, in particular strain FZB42 (e.g. RHIZOVITAL® from ABiTEP, DE) + TX; Bacillus amyloliquefaciens BS27 (Accession No. NRRL B-5015) + TX; Bacillus cereus family member EE128 (NRRL No. B-50917) + TX; Bacillus cereus family member EE349 (NRRL No. B-50928) + TX; Bacillus cereus, in particular strain BP01 (ATCC 55675, e.g. MEPICHLOR® from Arysta Lifescience, US) + TX; Bacillus firmus, in particular strain CNMC 1-1582 (e.g. VOTIVO® from BASF SE) + TX; Bacillus mycoides BT155 (NRRL No. B-50921) + TX; Bacillus mycoides EE118 (NRRL No. B-50918) + TX; Bacillus mycoides EE141 (NRRL No. B-50916) + TX; Bacillus mycoides BT46-3 (NRRL No. B-50922) + TX; Bacillus pumilus, in particular strain QST2808 (Accession No. NRRL No. B-30087) + TX; Bacillus pumilus, in particular strain GB34 (e.g. YIELD SHIELD® from Bayer Crop Science, DE) + TX; Bacillus siamensis, in particular strain KCTC 13613T + TX; Bacillus subtilis, in particular strain QST713/AQ713 (having NRRL Accession No. B-21661 and described in U.S. Patent No. 6,060,051, available as SERENADE® OPTI or SERENADE® ASO from Bayer CropScience LP, US) + TX; Bacillus subtilis, in particular strain AQ30002 (Accession No. NRRL No. B-50421 and described in U.S. Patent Application No.13/330,576) + TX; Bacillus subtilis, in particular strain AQ30004 (NRRL No. B-50455 and described in U.S. Patent Application No. 13/330,576) + TX; Bacillus subtilis strain BU1814, (available as TEQUALIS® from BASF SE), Bacillus subtilis rm303 (RHIZOMAX® from Biofilm Crop Protection) + TX; Bacillus thuringiensis BT013A (NRRL No. B-50924) also known as Bacillus thuringiensis 4Q7 + TX; a mixture of Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (available as QUARTZO® (WG), PRESENCE® (WP) from FMC Corporation) + TX; Bacillus subtilis, in particular strain MBI 600 (e.g. SUBTILEX® from BASF SE) + TX; Bacillus tequilensis, in particular strain NII-0943 + TX; Bradyrhizobium japonicum (e.g. OPTIMIZE® from Novozymes) + TX; Delftia acidovorans, in particular strain RAY209 (e.g. BIOBOOST® from Brett Young Seeds) + TX; Mesorhizobium cicer (e.g., NODULATOR from BASF SE) + TX; Lactobacillus sp. (e.g. LACTOPLANT® from LactoPAFI) + TX; Rhizobium leguminosarium biovar viciae (e.g., NODULATOR from BASF SE) + TX; Pseudomonas proradix (e.g. PRORADIX® from Sourcon Padena) + TX; Pseudomonas aeruginosa, in particular strain PN1 + TX; Rhizobium leguminosarum, in particular bv. viceae strain Z25 (Accession No. CECT 4585) + TX; Paenibacillus polymyxa, in particular strain AC-1 (e.g. TOPSEED® from Green Biotech Company Ltd.) + TX; Serratia marcescens, in particular strain SRM (Accession No. MTCC 8708) + TX; Sinorhizobium meliloti strain NRG-185-1 (NITRAGIN® GOLD from Bayer CropScience) + TX; Thiobacillus sp. (e.g. CROPAID® from Cropaid Ltd UK) + TX; and (3.2) fungi, examples of which are Purpureocillium lilacinum (previously known as Paecilomyces lilacinus) strain 251 (AGAL 89/030550, e.g. BioAct from Bayer CropScience Biologics GmbH) + TX; Penicillium bilaii, strain ATCC 22348 (e.g. JumpStart® from Acceleron BioAg), Talaromyces flavus, strain V117b + TX; Trichoderma atroviride strain CNCM 1-1237 (e.g. Esquive® WP from Agrauxine, FR), Trichoderma viride, e.g. strain B35 (Pietr et al., 1993, Zesz. Nauk. A R w Szczecinie 161: 125-137) + TX; Trichoderma atroviride strain LC52 (also known as Trichoderma atroviride strain LU132, e.g. Sentinel® from Agrimm Technologies Limited) + TX; Trichoderma atroviride strain SC1 described in WO2009/116106) + TX; Trichoderma asperellum strain kd (e.g. T-Gro from Andermatt Biocontrol) + TX; Trichoderma asperellum strain (Eco-T from Plant Health Products, ZA) + TX, Trichoderma harzianum strain T-22 (e.g. Trianum-P from Andermatt Biocontrol or Koppert) + TX; Myrothecium verrucaria strain AARC-0255 (e.g. DiTera™ from Valent Biosciences) + TX; Penicillium bilaii strain ATCC ATCC20851 + TX; Pythium oligandrum strain M1 (ATCC 38472, e.g. Polyversum from Bioprepraty, CZ) + TX; Trichoderma virens strain GL-21 (e.g. SoilGard® from Certis, USA) + TX; Verticillium albo-atrum (formerly V. dahliae) strain WCS850 (CBS 276.92, e.g. Dutch Trig from Tree Care Innovations) + TX; Trichoderma atroviride, in particular strain no. V08/002387, strain no. NMI No. V08/002388, strain no. NMI No. V08/002389, strain no. NMI No. V08/002390 + TX; Trichoderma harzianum strain ITEM 908, Trichoderma harzianum, strain TSTh20 + TX; Trichoderma harzianum strain 1295-22 + TX; Pythium oligandrum strain DV74 + TX; Rhizopogon amylopogon (e.g. Myco-Sol from Agri-Enterprise, LLC, formerly Helena Chemical Company) + TX; Rhizopogon fulvigleba (e.g. Myco-Sol from Agri-Enterprise, LLC, formerly Helena Chemical Company) + TX; Trichoderma virens strain GI-3 + TX; (4) insecticidally active biological control agents selected from (4.1) bacteria, examples of which are Agrobacterium radiobacter strain K84 (Galltrol from AgBiochem Inc.) + TX; Bacillus amyloliquefaciens, in particular strain PTS-4838 (e.g. AVEO from Valent Biosciences, US) + TX; Bacillus firmus, in particular strain CNMC 1-1582 (e.g. VOTIVO® from BASF SE) + TX; Bacillus mycoides, isolate J. (e.g. BmJ from Certis USA LLC.) + TX; Bacillus sphaericus, in particular Serotype H5a5b strain 2362 (strain ABTS-1743) (e.g. VECTOLEX® from Valent BioSciences, US) + TX; Bacillus thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372, e.g. XENTARI® from Valent BioSciences) + TX; Bacillus thuringiensis subsp. aizawai, in particular serotype H-7 (e.g. FLORBAC® WG from Valent BioSciences, US) + TX; Bacillus thuringiensis israelensis strain BMP 144 (e.g. AQUABAC® by Becker Microbial Products IL) + TX; Bacillus thuringiensis subsp. israelensis (serotype H-14) strain AM65-52 (Accession No. ATCC 1276) (e.g. VECTOBAC® by Valent BioSciences, US) + TX; Bacillus thuringiensis subsp. aizawai strain GC-91 + TX; Bacillus thuringiensis var. Colmeri (e.g. TIANBAOBTC by Changzhou Jianghai Chemical Factory) + TX; Bacillus thuringiensis var. japonensis strain Buibui + TX; Bacillus thuringiensis subsp. kurstaki strain BMP 123 (from Becker Microbial Products, IL, BARITONE from Bayer CropScience) + TX; Bacillus thuringiensis subsp. kurstaki strain HD-1 (e.g. DIPEL® ES from Valent BioSciences, US) + TX; Bacillus thuringiensis var. kurstaki strain EVB-113-19 (e.g., BIOPROTEC® from AEF Global) + TX; Bacillus thuringiensis subsp. kurstaki strain ABTS 351 + TX; Bacillus thuringiensis subsp. kurstaki strain PB 54 + TX; Bacillus thuringiensis subsp. kurstaki strain SA 11 (JAVELIN from Certis, US) + TX; Bacillus thuringiensis subsp. kurstaki strain SA 12 (THURICIDE from Certis, US) + TX; Bacillus thuringiensis subsp. kurstaki strain EG 2348 (LEPINOX® from Certis, US) + TX; Bacillus thuringiensis subsp. kurstaki strain EG 7841 (CRYMAX® from Certis, US) + TX; Bacillus thuringiensis subsp. tenebrionis strain NB 176 (SD-5428, e.g. NOVODOR® FC from BioFa DE) + TX; Brevibacillus laterosporus (LATERAL® from Ecolibrium Biologicals) + TX; Burkholderia spp., in particular Burkholderia rinojensis strain A396 (also known as Burkholderia rinojensis strain MBI 305) (Accession No. NRRL B-50319); WO 2011/106491 and WO 2013/032693; e.g. MBI206 TGAI and ZELTO® from Marrone Bio Innovations) + TX; Chromobacterium subtsugae, in particular strain PRAA4-1T (e.g. MBI-203; e.g. GRANDEVO® from Marrone Bio Innovations) + TX; Lecanicillium muscarium Ve6 (MYCOTAL from Koppert) + TX; Paenibacillus popilliae (formerly Bacillus popilliae + TX; e.g. MILKY SPORE POWDER™ or MILKY SPORE GRANULAR™ from St. Gabriel Laboratories) + TX; Pasteuria nishizawae strain Pn1 (CLARIVA from Syngenta/ChemChina) + TX;Serratia entomophila (e.g. INVADE® by Wrightson Seeds) + TX; Serratia marcescens, in particular strain SRM (Accession No. MTCC 8708) + TX;Trichoderma asperellum (TRICHODERMAX from Novozymes) + TX; Wolbachia pipientis ZAP strain (e.g., ZAP MALES® from MosquitoMate) + TX; and (4.2) fungi, examples of which are Beauveria bassiana strain ATCC 74040 (e.g. NATURALIS® from Intrachem Bio Italia) + TX; Beauveria bassiana strain GHA (Accession No. ATCC74250, e.g. BOTANIGUARD® ES and MYCONTROL-O® from Laverlam International Corporation) + TX; Beauveria bassiana strain ATP02 (Accession No. DSM 24665) + TX; Isaria fumosorosea (previously known as Paecilomyces fumosoroseus) strain Apopka 97 (PREFERAL® from SePRO) + TX; Metarhizium anisopliae 3213-1 (deposited under NRRL accession number 67074 disclosed in WO 2017/066094; Pioneer Hi-Bred International) + TX; Metarhizium robertsii 15013-1 (deposited under NRRL accession number 67073) + TX; Metarhizium robertsii 23013-3 (deposited under NRRL accession number 67075) + TX; Paecilomyces lilacinus strain 251 (MELOCON® from Certis, US) + TX; Zoophtora radicans + TX; (5) Viruses selected from the group consisting of Adoxophyes orana (summer fruit tortrix) granulosis virus (GV) + TX; Cydia pomonella (codling moth) granulosis virus (GV) + TX; Helicoverpa armigera (cotton bollworm) nuclear polyhedrosis virus (NPV) + TX; Spodoptera exigua (beet armyworm) mNPV + TX; Spodoptera frugiperda (fall armyworm) mNPV + TX; Spodoptera littoralis (African cotton leafworm) NPV + TX; (6) Bacteria and fungi which can be added as ’inoculant’ to plants or plant parts or plant organs and which, by virtue of their particular properties, promote plant growth and plant health selected from Agrobacterium spp. + TX; Azorhizobium caulinodans + TX; Azospirillum spp. + TX; Azotobacter spp. + TX; Bradyrhizobium spp. + TX; Burkholderia spp., in particular Burkholderia cepacia (formerly known as Pseudomonas cepacia) + TX; Gigaspora spp., or Gigaspora monosporum + TX; Glomus spp. + TX; Laccaria spp. + TX; LactoBacillus buchneri + TX; Paraglomus spp. + TX; Pisolithus tinctorus + TX; Pseudomonas spp. + TX; Rhizobium spp., in particular Rhizobium trifolii + TX; Rhizopogon spp. + TX; Scleroderma spp. + TX; Suillus spp. + TX; Streptomyces spp. + TX; (7) Plant extracts and products formed by microorganisms including proteins and secondary metabolites which can be used as biological control agents, selected from Allium sativum (NEMGUARD from Eco-Spray; BRALIC from ADAMA) + TX; Armour-Zen + TX; Artemisia absinthium + TX; Azadirachtin (e.g. AZATIN XL from Certis, US) + TX; Biokeeper WP + TX; Brassicaceae extract, in particular oilseed rape powder or mustard powder + TX; Cassia nigricans + TX; Celastrus angulatus + TX; Chenopodium anthelminticum + TX; Chitin + TX; Dryopteris filix-mas + TX; Equisetum arvense + TX; Fortune Aza + TX; Fungastop + TX; Chenopodium quinoa saponin extract from quinoa seeds (e.g. Heads Up® (Saponins of Quinoa) from Heads Up plant Protectants, CA) + TX; naturally occurring Blad polypeptide extracted from Lupin seeds (PROBLAD® from Certis EU) + TX; naturally occurring Blad polypeptide extracted from Lupin seeds (FRACTURE® from FMC) + TX; Pyrethrum/Pyrethrins + TX; Quassia amara + TX; Quercus + TX; Quillaja extract (QL AGRI 35 from BASF) + TX; Reynoutria sachalinensis extract (REGALLIA®, REGALIA® MAXX from Marrone Bio) + TX; "Requiem ™ Insecticide" + TX; Rotenone + TX; ryania/ryanodine + TX; Symphytum officinale + TX; Tanacetum vulgare + TX; Thymol + TX; Thymol mixed with Geraniol (CEDROZ from Eden Research) + TX; Thymol mixed with Geraniol and Eugenol (MEVALONE® from Eden Research) + TX; Triact 70 + TX; TriCon + TX; Tropaeulum majus + TX; Melaleuca alternifolia extract (TIMOREX GOLD from STK) + TX; Urtica dioica + TX; Veratrin + TX; and Viscum album + TX; and a safener, such as benoxacor + TX, cloquintocet (including cloquintocet-mexyl) + TX, cyprosulfamide + TX, dichlormid + TX, fenchlorazole (including fenchlorazole-ethyl) + TX, fenclorim + TX, fluxofenim + TX, furilazole + TX, isoxadifen (including isoxadifen-ethyl) + TX, mefenpyr (including mefenpyr-diethyl) + TX, metcamifen + TX and oxabetrinil + TX. In addition, the compositions of the invention may also be applied with one or more systemically acquired resistance inducers (“SAR” inducer). SAR inducers are known and described in, for example, United States Patent No. US 6,919,298 and include, for example, salicylates and the commercial SAR inducer acibenzolar-S-methyl. The compounds of formula (I) as defined in the present invention are normally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations, which influence the growth of plants. They can also be selective herbicides or non- selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation. The compounds of formula (I) as defined in the present invention may be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula (I) as defined in any one of embodiments 1 to 43 or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants. The invention therefore provides a composition, preferably a fungicidal composition, comprising at least one compound of formula (I) as defined in the present invention, an agriculturally acceptable carrier and optionally an adjuvant. An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use. Agricultural carriers are well known in the art. Preferably said composition may comprise at least one or more pesticidally active compounds, for example an additional fungicidal active ingredient in addition to the compound of formula (I) as defined in the present invention. A further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of non-living materials by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula (I) as defined in the present invention or of a preferred individual compound as above-defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials. Controlling or preventing means reducing infestation by insects or by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated. A preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, which comprises the application of a compound of formula (I) as defined in the present invention, or an agrochemical composition which contains at least one of said compounds, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen or insect. However, the compounds of formula (I) as defined in the present invention can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula (I) as defined in any the present invention may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation. A formulation, e.g. a composition containing the compound of formula (I) as defined in the present invention, and, if desired, a solid or liquid adjuvant or monomers for encapsulating the compound of formula (I) as defined in the present invention, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active compounds (surfactants). The application methods for the compositions, that is the methods of controlling pathogens of the abovementioned type, such as spraying, atomizing, dusting, brushing on, dressing, scattering or pouring - which are to be selected to suit the intended aims of the prevailing circumstances - and the use of the compositions for controlling pathogens of the abovementioned type are other subjects of the invention. Typical rates of concentration are between 0.1 and 1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient. The rate of application per hectare is preferably 1g to 2000 g of active ingredient per hectare, more preferably 10 to 1000 g/ha, most preferably 10 to 600 g/ha. When used as seed drenching agent, convenient dosages are from 10mg to 1g of active substance per kg of seeds. When the combinations of the present invention are used for treating seed, rates of 0.001 to 50 g of a compound of formula (I) per kg of seed, preferably from 0.01 to 10g per kg of seed are generally sufficient. Suitably, a composition comprising a compound of formula (I) as defined in the present invention according to the present invention is applied either preventative, meaning prior to disease development or curative, meaning after disease development. The compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants. Such compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients such as surfactants, biocides, anti-freeze, stickers, thickeners and compounds that provide adjuvancy effects). Also conventional slow release formulations may be employed where long lasting efficacy is intended. Particularly formulations to be applied in spraying forms, such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain surfactants such as wetting and dispersing agents and other compounds that provide adjuvancy effects, e.g. the ondensation product of formaldehyde with naphthalene sulphonate, an alkylarylsulphonate, a lignin sulphonate, a fatty alkyl sulphate, and ethoxylated alkylphenol and an ethoxylated fatty alcohol. A seed dressing formulation is applied in a manner known per se to the seeds employing the combination of the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds. Such seed dressing formulations are known in the art. Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules. In general, the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula (I) as defined in the present invention together with component (B) and (C), and optionally other active agents, particularly microbiocides or conservatives or the like. Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations. Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations. EXAMPLES The Examples which follow serve to illustrate the invention. Certain compounds of the invention can be distinguished from known compounds by virtue of greater efficacy at low application rates, which can be verified by the person skilled in the art using the experimental procedures outlined in the Examples,. Compounds of Formula (I) may possess any number of benefits including, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile (including improved crop tolerance), improved physico-chemical properties, or increased biodegradability). Throughout this description, temperatures are given in degrees Celsius (°C) and “MP” means melting point. LC/MS means Liquid Chromatography Mass Spectrometry and the description of the apparatus and the methods are described below. Formulation Examples Wettable powders a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % sodium lignosulfonate 5 % 5 % - sodium lauryl sulfate 3 % - 5 % sodium diisobutylnaphthalenesulfonate - 6 % 10 % phenol polyethylene glycol ether - 2 % - (7-8 mol of ethylene oxide) highly dispersed silicic acid 5 % 10 % 10 % Kaolin 62 % 27 % - The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration. Powders for dry seed treatment a) b) c) active ingredient [compound of formula (I)] 25 % 50 % 75 % light mineral oil 5 % 5 % 5 % highly dispersed silicic acid 5 % 5 % - Kaolin 65 % 40 % - Talcum - 20% The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording powders that can be used directly for seed treatment. Emulsifiable concentrate active ingredient [compound of formula (I)] 10 % octylphenol polyethylene glycol ether 3 % (4-5 mol of ethylene oxide) calcium dodecylbenzenesulfonate 3 % castor oil polyglycol ether (35 mol of ethylene oxide) 4 % Cyclohexanone 30 % xylene mixture 50 % Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water. Dusts a) b) c) Active ingredient [compound of formula (I)] 5 % 6 % 4 % talcum 95 % - - Kaolin - 94 % - mineral filler - - 96 % Ready-for-use dusts are obtained by mixing the active ingredient with the carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry dressings for seed. Extruder granules Active ingredient [compound of formula (I)] 15 % sodium lignosulfonate 2 % carboxymethylcellulose 1 % Kaolin 82 % The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air. Coated granules Active ingredient [compound of formula (I)] 8 % polyethylene glycol (mol. wt.200) 3 % Kaolin 89 % The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner. Suspension concentrate active ingredient [compound of formula (I)] 40 % propylene glycol 10 % nonylphenol polyethylene glycol ether (15 mol of ethylene oxide) 6 % Sodium lignosulfonate 10 % carboxymethylcellulose 1 % silicone oil (in the form of a 75 % emulsion in water) 1 % Water 32 % The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Flowable concentrate for seed treatment active ingredient [compound of formula (I)] 40 % propylene glycol 5 % copolymer butanol PO/EO 2 % tristyrenephenole with 10-20 moles EO 2 % 1,2-benzisothiazolin-3-one (in the form of a 20% solution in water) 0.5 % monoazo-pigment calcium salt 5 % Silicone oil (in the form of a 75 % emulsion in water) 0.2 % Water 45.3 % The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water. Using such dilutions, living plants as well as plant propagation material can be treated and protected against infestation by microorganisms, by spraying, pouring or immersion. Slow Release Capsule Suspension 28 parts of a combination of the compound of formula (I) are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed. The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns. The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose. Analytical Methods Method A: Equipment: Shimadzu LCMS 2020 Mass Spectrometer; Column: HALO C182.7 µm, 3.0 mm × 30 mm; Mobile Phase: MeCN (with either 0.05% HCOOH or 0.05% TFA) - Water (with either 0.05% HCOOH or 0.05% TFA); Gradient: MeCN from 5% to 95% over 1.4 min, hold 0.6 min, total run time is 2.5 min; Flow rate: 1.8 mL/min; Column temperature: 50 °C; Wavelength: 214 and 254 nm PDA. Method B: Spectra were recorded on a Mass Spectrometer from Waters (Acquity QDa Mass Spectrometer) equipped with an electrospray source (Polarity: Positive and Negative Polarity Switch), Capillary: 0.8 kV, Cone range: 25 V, Extractor: V (No extractor voltage for QDa detector) Source Temperature: 120°C, Desolvation Temperature: 600°C, Cone Gas Flow: 50 L/h, Desolvation Gas Flow: 1000 L/h, Mass range: 110 to 850 Da) and an Acquity UPLC from Waters: Quaternary solvent manager, heated column compartment , diode-array detector. Column: Acquity UPLC HSS T3 C18, 1.8 µm, 30 x 2.1 mm, Temp: 40 °C, DAD Wavelength range (nm): 200 to 400, Solvent Gradient: A = water + 5% Acetonitrile + 0.1 % HCOOH, B= Acetonitrile + 0.05 % HCOOH: gradient: 0 min 10% B; 0.-0.2 min 10-50% B; 0.2-0.6 min 50-100% B; 0.6-1.3 min 100% B; 1.3-1.4 min 100-10% B; 1.4-1.6 min 10% B; Flow (mL/min) 0.6. Method C: Spectra were recorded on a Mass Spectrometer from Waters Corporation (SQD, SQDII or QDA Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive and negative ions), Capillary: 0.8-3.00 kV, Cone: 5-30 V, Source Temperature: 120-150°C, Desolvation Temperature: 350-600°C, Cone Gas Flow: 50-150 l/h, Desolvation Gas Flow: 650-1000 l/h, Mass range: 110 to 950 Da and an Acquity UPLC from Waters Corporation: Binary pump, heated column compartment, diode- array detector and ELSD. Column: Waters UPLC HSS T3, 1.8 µm, 30 x 2.1 mm, Temp: 60 °C, DAD Wavelength range (nm): 210 to 400, Runtime: 1.5 min; Solvents: A = water + 5% MeOH + 0.05 % HCOOH, B= Acetonitrile + 0.05 % HCOOH; Flow (mL/min) 0.85, Gradient: 10% B isocratic for 0.2 min, then 10-100% B in 1.0 min, 100% B isocratic for 0.2min, 100-10% B in 0.05min, 10% B isocratic for 0.05 min Method D: Spectra were recorded on a ACQUITY Mass Spectrometer from Waters Corporations (SQD or SQDII Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.0 kV, Cone: 30V, Extractor: 3.00 V, Source Temperature: 150°C, Desolvation Temperature: 400°C, Cone Gas Flow: 60 L/hr, Desolvation Gas Flow: 700 L/hr, Mass range: 140 to 800 Da) and an ACQUITY UPLC from Waters Corporations with solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3, 1.8 µm, 30 x 2.1 mm, Temp: 60 °C, DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A = Water/Methanol 9:1 + 0.1% formic acid, B= Acetonitrile + 0.1% formic acid, gradient: 0-100% B in 2.5 min; Flow (mL/min) 0.75. Method E: Spectra were recorded on a Mass Spectrometer from Agilent (Single quad mass spectrometer) equipped with a Multimode- Electron Spray and APCI (Polarity: positive and negative ions), Capillary: 4.00 kV, Corona Current 4.0 µA, Charging Voltage: 2.00 kV, Nitrogen Gas Flow: 12.0 L/min, Nebulizer Pressure: 40 psig, Mass range: 100 to 1000 m/z), dry gas temperature 250 °C, Vaporizer temperature 200 °C and an UPLC from Waters: quaternary pump, heated column compartment, Variable wave length detector. Column: X-Bridge BEH C18, 2.5 µm (2.1*50 mm), column Temp: Ambient, Wavelength (nm): 215 nm, Gradient: A = 0.05% TFA in water, B = 0.05% TFA in Acetonitrile. Gradient: time/%B: 0/5, 1/5, 5/70, 7/95, 8.5/95, 8.6/5, 10/5; Flow rate: 0.6 mL/min. Method F: Spectra were recorded on a on a Mass Spectrometer from Agilent (Single quad mass spectrometer) equipped with Electron Spray (Polarity: positive and negative ions), Capillary: 4.00 kV, Charging Voltage: 2.00 kV, Nitrogen Gas Flow: 12.0 L/min, Nebulizer Pressure: 40 psig, Mass range: 100 to 1000 m/z, dry gas temperature 250 °C, Vaporizer temperature 200 °C and an UPLC from Waters: quaternary pump, heated column compartment, Variable wave length detector. Column: Kinetex Evo_50 mm, 1.7 µm (2.1*50 mm) column, Temp: Ambient, Wavelength (nm): 200-400 nm, Gradient: A = acetonitrile, B = 10 mM ammonium formate in water. Gradient time/%A: 0/2, 0.2/2, 1.5/45, 2.4/95, 3.3/2, 3.5/2; Flow rate: 0.5 mL/min. The below Table A gathers for compounds of formula (I): - LC/MS data, such as retention time (RT), [M+H]+, - the type of methods, and/or - melting point (MP). Table A: Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 1 methyl N-[5-[6-[4-(4- 0.92 461 A 236- fluorophenyl)-5,6-dihydro-1,2,4- 239 oxadiazin-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 2 methyl N-[5-[8-cyclopropyl-6-[4- 0.90 500 A 226- (4-fluoro-3-methoxy-phenyl)- 228 1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 3 methyl N-[5-[6-[4-(4-fluoro-3- 0.93 491 A 157- methoxy-phenyl)-5,6-dihydro- 161 1,2,4-oxadiazin-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 4 methyl N-[5-[6-[2-(4-fluoro-3- 0.71 460 C 123- methoxy-phenyl)-1,2,4-triazol-3- 133 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 5 methyl N-[5-[6-[4-(4-fluoro-3- 0.17 472 B methyl-phenyl)-5-methyl-1,2,4- triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 6 methyl N-[5-[6-[4-(4- 0.16 458 B fluorophenyl)-5-methyl-1,2,4- triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 7 methyl N-[5-[6-[4-(4-fluoro-3- 1.00 518 B 215- methoxy-phenyl)-5- 217 (methoxymethyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 8 methyl N-[5-[6-[1-(4-fluoro-3- 0.93 473 A 198- methoxy-phenyl)imidazol-2-yl]- 200 8-methyl-imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate 9 methyl N-[5-[6-[5-(4-fluoro-3- 0.98 460 A 200- methoxy-phenyl)-1,2,4-triazol-1- 203 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 10 methyl N-[5-[6-[4-(4-fluoro-3- 0.95 477 A 206- methoxy-phenyl)-5,6-dihydro- 207 1,2,4-oxadiazin-3-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 11 methyl N-[5-[6-[1-(4-fluoro-3- 0.67 459 C 190- methoxy-phenyl)imidazol-2- 213 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 12 methyl N-[5-[6-[4-(4-fluoro-3- 1.04 502 B 212- methyl-phenyl)-5- 215 (methoxymethyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 13 methyl N-[5-[6-[4-(3,4- 0.92 506 B 220- difluorophenyl)-5- 222 (methoxymethyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 14 methyl N-[5-[6-[4-(4- 0.18 488 B 195- fluorophenyl)-5- 197 (methoxymethyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 15 methyl N-[5-[8-cyclopropyl-6-[4- 0.16 470 B 241- (4-fluorophenyl)-1,2,4-triazol-3- 243 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 16 methyl N-[5-[6-[2-(3,4- 0.73 462 B 208- difluorophenyl)-1,2,4-triazol-3- 210 yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 17 methyl N-[5-[6-[4-(4-fluoro-3- 0.20 488 B 238- methoxy-phenyl)-5-methyl-1,2,4- 240 triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 18 methyl N-[5-[6-[1-(4- 0.93 443 A 240- fluorophenyl)imidazol-2-yl]-8- 241 methyl-imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate 19 methyl N-[5-[6-[5-(4-fluoro-3- 0.93 487 A 202- methoxy-phenyl)-1,3-dimethyl- 205 pyrazol-4-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 20 methyl N-[5-[6-[5-(4-fluoro-3- 0.90 473 A 192 – methoxy-phenyl)-1-methyl- 195 pyrazol-4-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 21 methyl N-[5-[6-[5-(4-fluoro-3- 1.03 460 A 194- methoxy-phenyl)oxazol-4- 196 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 22 methyl N-[5-[6-[5-(4-fluoro-3- 0.92 473 A 198.6 methoxy-phenyl)-1-methyl- - imidazol-4-yl]imidazo[1,2- 199.1 a]pyridin-3-yl]-2- pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 23 methyl N-[5-[6-[5-(4- 0.89 443 A 160- fluorophenyl)-1-methyl-imidazol- 163 4-yl]imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate 24 methyl N-[5-[6-[4-(4- 0.90 447 A 125- fluorophenyl)-5,6-dihydro-1,2,4- 130 oxadiazin-3-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 25 methyl N-[5-[6-[2-(4-fluoro-3- 1.59 474 F 245- methoxy-phenyl)-1,2,4-triazol-3- 250 yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 26 methyl N-[5-[6-[4-(4-fluoro-3- 0.65 474 C methoxy-phenyl)-5-methyl-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate 27 methyl N-[5-[6-[2-(4-chloro-3- 0.73 476 C 220- methoxy-phenyl)-1,2,4-triazol-3- 222 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 28 methyl N-[5-[6-[3-(4- 2.77 441 E 210- fluorophenyl)pyrazin-2- 215 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 29 methyl N-[5-[6-[4-(4-fluoro-3- 0.38 474 B 244- methoxy-phenyl)-1,2,4-triazol-3- 246 yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 30 methyl N-[5-[6-[4-(4-fluoro-3- 0.93 504 B 206- methoxy-phenyl)-5- 208 (methoxymethyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 31 methyl N-[5-[6-[4-(4-fluoro-3- 1.00 473 A 189.1 methoxy-phenyl)-1-methyl- - pyrazol-3-yl]imidazo[1,2- 189.5 a]pyridin-3-yl]-2- pyridyl]carbamate 32 methyl N-[5-[6-[4-(4-fluoro-3- 1.05 477 A 199.3 methoxy-phenyl)-5-oxo-1,2,4- - oxadiazol-3-yl]imidazo[1,2- 201.1 a]pyridin-3-yl]-2- pyridyl]carbamate 33 methyl N-[5-[6-[2-(4-fluoro-3- 0.72 474 C methoxy-phenyl)-5-methyl-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate 34 methyl N-[5-[6-[4-(4- 0.52 444 B 256- fluorophenyl)-1,2,4-triazol-3-yl]- 258 8-methyl-imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate 35 methyl N-[5-[6-[4-(4-fluoro-3- 0.92 458 B 224- methyl-phenyl)-1,2,4-triazol-3- 226 yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 36 methyl N-[5-[6-[2-(3,4- 1.34 448 B 157- difluorophenyl)-1,2,4-triazol-3- 159 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 37 methyl N-[5-[6-[5-(4- 1.02 457 A 199- fluorophenyl)-1,3-dimethyl- 201 pyrazol-4-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 38 methyl N-[5-[6-[5-(4- 0.93 430 A 201- fluorophenyl)-1,2,4-triazol-1- 206 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 39 methyl N-[5-[6-[4-(4-fluoro-3- 0.70 429 C 237- methoxy-phenyl)-1H-pyrazol-3- 241 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 40 methyl N-[5-[6-[4-(4- 0.97 443 A 197- fluorophenyl)-1-methyl-pyrazol- 198 3-yl]imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate 41 methyl N-[5-[6-[3-(4- 2.39 443 E 245- fluorophenyl)-5-methyl-imidazol- 250 4-yl]imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate 42 methyl N-[5-[6-[4-(4- 0.63 444 C fluorophenyl)-5-methyl-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate 43 methyl N-[5-[6-[1-(4- 0.67 215 C fluorophenyl)imidazol-2- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 44 methyl N-[5-[6-[2-(4- 0.69 430 C fluorophenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 45 methyl N-[5-[6-[4-(4-fluoro-3- 0.90 488 B 243- methyl-phenyl)-5- 245 (methoxymethyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 46 methyl N-[5-[6-[4-(3,4- 0.87 492 B 224- difluorophenyl)-5- 226 (methoxymethyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 47 methyl N-[5-[6-[2-(4- 3.85 432 E fluorophenyl)pyrrolidin-1- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 48 methyl N-[5-[6-[(2R)-2-(4- 0.68 446 C fluorophenyl)-5-oxo-pyrrolidin-1- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 49 methyl N-[5-[6-[2-(4- 0.68 446 C fluorophenyl)-5-oxo-pyrrolidin-1- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 50 methyl N-[5-[6-[4-(4- 0.96 474 B 222- fluorophenyl)-5- 224 (methoxymethyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 51 methyl N-[5-[6-[2-(4-fluoro-3- 0.89 473 E 245- methoxy-phenyl)-5-methyl- 248 imidazol-1-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 52 methyl N-[5-[6-[2-(4- 0.85 443 A 244- fluorophenyl)-5-methyl-imidazol- 247 1-yl]imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate 53 methyl N-[5-[6-[5-(4-fluoro-3- 1.39 473 A 210- methoxy-phenyl)-2-methyl- 213 imidazol-1-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 54 methyl N-[5-[6-[5-(4- 1.39 443 A 210- fluorophenyl)-2-methyl-imidazol- 213 1-yl]imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 55 methyl N-[5-[6-[5-(4- 0.87 443 A 240- fluorophenyl)-1-methyl-pyrazol- 243 4-yl]imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate 56 methyl N-[5-[6-[4-(4-fluoro-3- 1.01 473 A 202- methoxy-phenyl)-2-methyl- 205 pyrazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 57 methyl N-[5-[6-[4-(4- 1.05 443 A 216- fluorophenyl)-2-methyl-pyrazol- 217 3-yl]imidazo[1,2-a]pyridin-3-yl]- 2-pyridyl]carbamate 58 methyl N-[5-[6-[5-(4-fluoro-3- 1.20 459 A methoxy-phenyl)pyrazol-1- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 59 methyl N-[5-[6-[5-(4- 0.99 429 A 240- fluorophenyl)pyrazol-1- 243 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 60 methyl N-[5-[6-[4-(4-fluoro-3- 0.87 460 A 191- methoxy-phenyl)oxazol-5- 194 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 61 methyl N-[5-[6-[4-(4-fluoro-3- 1.07 460 A 210- methoxy-phenyl)isoxazol-3- 214 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 62 methyl N-[5-[6-[4-(4- 1.05 430 A 196- fluorophenyl)oxazol-5- 199 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 63 methyl N-[5-[6-[5-(4- 0.98 430 A 190- fluorophenyl)oxazol-4- 192 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 64 methyl N-[5-[6-[4-(4- 1.10 430 A 202- fluorophenyl)isoxazol-3- 204 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 65 methyl N-[5-[6-[4-(4- 0.88 429 A 255- fluorophenyl)-1H-pyrazol-3- 258 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 66 methyl N-[5-[6-[4-(4- 1.02 447 A 219- fluorophenyl)-5-oxo-1,2,4- 224 oxadiazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 67 ethyl 3-(4-fluorophenyl)-2-[3-[6- 3.12 501 E 240- (methoxycarbonylamino)-3- 245 pyridyl]imidazo[1,2-a]pyridin-6- yl]imidazole-4-carboxylate 68 methyl N-[5-[6-[(2R)-2-(4- 0.68 446 C fluorophenyl)-5-oxo-pyrrolidin-1- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 69 methyl N-[5-[6-[5-(4- 2.96 441 E 235- fluorophenyl)pyrimidin-4- 240 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 70 methyl N-[5-[6-[4-(4- 2.65 441 E 185- fluorophenyl)pyridazin-3- 190 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 71 methyl N-[5-[6-[5-cyano-1-(4- 2.85 454 E fluorophenyl)imidazol-2- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 72 methyl N-[5-[6-[5-chloro-1-(4- 3.15 463 E 240- fluorophenyl)imidazol-2- 245 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 73 methyl N-[5-[6-[5-chloro-2-(4- 1.81 464 F 235- fluorophenyl)-1,2,4-triazol-3- 240 yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 74 methyl N-[5-[6-[5-cyano-2-(4- 0.84 455 C fluorophenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 75 methyl N-[5-[6-[4-(4- 0.62 430 C fluorophenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 76 methyl N-[5-[6-[2-(4- 0.70 429 C fluorophenyl)pyrazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 77 methyl N-[5-[6-[4-(3,4- 0.98 461 B 266- difluorophenyl)-1,2,4-triazol-3- 268 yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 78 methyl N-[5-[6-[4-(6-methoxy-3- 0.90 456 B 220- pyridyl)-1,2,4-triazol-3-yl]-8- 222 methyl-imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 79 N-[4-[6-[2-(4-fluoro-3-methoxy- 0.85 473 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]-2-methoxy-acetamide 80 N-[4-[6-[2-(4-fluoro-3-methoxy- 0.91 469 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]cyclopropanecarboxa mide 81 1-ethyl-3-[4-[6-[2-(4-fluoro-3- 0.82 472 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]urea 82 3-[4-[6-[2-(4-fluoro-3-methoxy- 0.81 472 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]-1,1-dimethyl-urea 83 benzyl N-[4-[6-[2-(4-fluoro-3- 1.23 535 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate 84 1-ethyl-3-[5-[6-[2-(4-fluoro-3- 0.88 473 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]urea 85 N-[4-[6-[2-(4-fluoro-3-methoxy- 0.76 443 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]acetamide 86 N-[5-[6-[2-(4-fluoro-3-methoxy- 0.93 470 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]cyclopropanecarboxamid e Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 87 methyl N-[4-[6-[2-(4-fluoro-3- 0.87 459 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate 88 tert-butyl N-[5-[6-[2-(4-fluoro-3- 1.2 502 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 89 tert-butyl N-[4-[6-[2-(4-fluoro-3- 1.19 501 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate 90 N-[5-[6-[2-(4-fluoro-3-methoxy- 0.75 444 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]acetamide 91 methyl N-[5-[6-[5-(3-fluoro-4- 0.83 521 A 187- methylsulfonyl-phenyl)-1-methyl- 189 pyrazol-4-yl]imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 92 methyl N-[5-[6-[4-(4-fluoro-3- 0.78 460 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 93 N-[5-[6-[4-(4-fluoro-3-methoxy- 0.70 444 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]acetamide 94 tert-butyl N-[4-[6-[4-(4-fluoro-3- 1.12 501 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 95 methyl N-[4-[6-[4-(4-fluoro-3- 0.81 459 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate 96 tert-butyl N-[5-[6-[4-(4-fluoro-3- 1.12 502 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate 97 N-[4-[6-[4-(4-fluoro-3-methoxy- 0.70 443 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]acetamide 98 benzyl N-[4-[6-[4-(4-fluoro-3- 1.17 535 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]carbamate 99 3-[4-[6-[4-(4-fluoro-3-methoxy- 0.76 472 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]-1,1-dimethyl-urea 100 1-ethyl-3-[4-[6-[4-(4-fluoro-3- 0.77 472 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]urea 101 N-[4-[6-[4-(4-fluoro-3-methoxy- 0.85 469 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]cyclopropanecarboxa mide 102 N-[4-[6-[4-(4-fluoro-3-methoxy- 0.77 473 D phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3- yl]phenyl]-2-methoxy-acetamide Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 103 1-ethyl-3-[5-[6-[4-(4-fluoro-3- 0.80 473 D methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]urea 104 N-[5-[6-[4-(4-fluoro-3-methoxy- 0.72 458 D phenyl)-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]acetamide 105 tert-butyl N-[4-[6-[4-(4-fluoro-3- 1.12 515 D methoxy-phenyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]phenyl]carbamate 106 tert-butyl N-[5-[6-[4-(4-fluoro-3- 1.12 516 D methoxy-phenyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2- pyridyl]carbamate 107 methyl N-[4-[6-[4-(4-fluoro-3- 0.81 473 D methoxy-phenyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]phenyl]carbamate 108 N-[4-[6-[4-(4-fluoro-3-methoxy- 0.71 457 D phenyl)-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]acetamide 109 benzyl N-[4-[6-[4-(4-fluoro-3- 1.15 549 D methoxy-phenyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]phenyl]carbamate 110 3-[4-[6-[4-(4-fluoro-3-methoxy- 0.76 486 D phenyl)-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]-1,1-dimethyl-urea Entry IUPAC name Chemical structure RT [M+H] Method MP (min) +(measured) (°C) 111 1-ethyl-3-[4-[6-[4-(4-fluoro-3- 0.77 486 D methoxy-phenyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]phenyl]urea 112 N-[4-[6-[4-(4-fluoro-3-methoxy- 0.84 483 D phenyl)-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]cyclopropanecarboxa mide 113 N-[4-[6-[4-(4-fluoro-3-methoxy- 0.79 487 D phenyl)-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3- yl]phenyl]-2-methoxy-acetamide 114 1-ethyl-3-[5-[6-[4-(4-fluoro-3- 0.83 487 D methoxy-phenyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]urea Example 1: preparation of methyl N-[5-[6-[2-(4-fluorophenyl)-5-methyl-imidazol-1-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 52) N 3
Figure imgf000154_0001
(Compound 52) Step 1: Preparation of N-allyl-4-fluoro-benzamide O
Figure imgf000154_0002
A mixture of 4-fluorobenzoic acid (5.00 g, 35.7 mmol) and thionyl chloride (36.0 mL, 494 mmol, 13.8 eq.) was stirred at 50 °C for 3 hours before being concentrated under reduced pressure. In a second flask, potassium carbonate (4.93 g, 35.7 mmol, 1.00 eq.) was added to a solution of prop-2-en-1-amine (6.11 g, 107 mmol, 3.00 eq.) in dichloromethane (50.0 mL). The mixture of amine was added to the solution of the acid chloride in dichloromethane (50.0 mL). The resulting reaction mixture was stirred at room temperature for 24 hours, then it was diluted with saturated aqueous NaHCO3 solution and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford N-allyl-4-fluoro-benzamide as a white solid. LC/MS (method A) retention time = 0.97 min; [M+H]+ = 180.2 Step 2: Preparation of (1Z)-N-allyl-4-fluoro-benzimidoyl chloride
Figure imgf000155_0001
A solution of N-allyl-4-fluoro-benzamide (1.00 g, 5.58 mmol) in thionyl chloride (15.0 mL) was heated at 75 °C for 12 hours. The resulting mixture was concentrated under reduced pressure to afford crude (1Z)- N-allyl-4-fluoro-benzimidoyl chloride which was used for the next step without further purification. Step 3: Preparation of N'-allyl-N-(3-bromoimidazo[1,2-a]pyridin-6-yl)-4-fluoro-benzamidine
Figure imgf000155_0002
To a stirred solution of (1Z)-N-allyl-4-fluoro-benzimidoyl chloride (1.00 g, 5.06 mmol) in toluene (15.0 mL) was added 3-bromoimidazo[1,2-a]pyridine-6-amine (1.07 g, 5.06 mmol, 1.00 eq.) and N,N- diethylethanamine (2.82 mL, 20.2 mmol, 4.00 eq.) under a nitrogen atmosphere. The mixture was heated at 100 °C and stirred for 5 hours before it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford N'-allyl-N-(3-bromoimidazo[1,2-a]pyridin-6-yl)-4- fluoro-benzamidine as a grey solid. LC/MS (method A) retention time = 0.80 min; [M+H]+ = 373.1 Step 4: Preparation of 3-bromo-6-[2-(4-fluorophenyl)-5-methyl-imidazol-1-yl]imidazo[1,2-a]pyridine To a stirred solution of N'-allyl-N-(3-bromoimidazo[1,2-a]pyridin-6-yl)-4-fluoro-benzamidine (200 mg, 0.536 mmol) in xylene (10.0 mL) was added palladium acetate (24.1 mg, 0.107 mmol, 0.200 eq.). The resulting reaction mixture was heated at 170 °C under microwave irradiation for 1 hour. The reaction mixture was cooled, washed with petroleum ether, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate /petroleum ether) to afford 3- bromo-6-[2-(4-fluorophenyl)-5-methyl-imidazol-1-yl]imidazo[1,2-a]pyridine as a yellow oil. LC/MS (method A) retention time = 0.85 min; [M+H]+ = 371.1 Step 5: Preparation of methyl N-[5-[6-[2-(4-fluorophenyl)-5-methyl-imidazol-1-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 51) To a stirred solution of 3-bromo-6-[2-(4-fluorophenyl)-5-methyl-imidazol-1-yl]imidazo[1,2-a]pyridine (140 mg, 0.377 mmol) in a mixture of dioxane/water (2.50 mL, v/v = 4/1) was added methyl N-[5-)(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (157 mg, 0.566 mmol, 1.50 eq.), potassium carbonate (130 mg, 0.943 mmol, 2.50 eq.) and Pd(dppf)Cl2 (27.6 mg, 0.0377 mmol, 0.100 eq.) under nitrogen atmosphere. The mixture was stirred at 80 °C for 3 hours, cooled down to room temperature, diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford the desired target, which was further triturated with acetonitrile to ultimately afford methyl N-[5-[6-[2-(4- fluorophenyl)-5-methyl-imidazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid. LC/MS (method A) retention time = 0.85 min; [M+H]+ = 443.2 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 8.87 - 8.70 (m, 1H), 8.47 (d, J = 1.0 Hz, 1H), 8.01 - 7.90 (m, 3H), 7.76 (d, J = 9.4 Hz, 1H), 7.44 (dd, J = 8.8, 5.4 Hz, 2H), 7.20 (dd, J = 9.4, 1.8 Hz, 1H), 7.13 (t, J = 8.8 Hz, 2H), 6.94 (s, 1H), 3.70 (s, 3H), 2.09 (s, 3H). Example 2: preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 65) N
Figure imgf000157_0001
To a mixture of 6-bromo-3-chloro-imidazo[1,2-a]pyridine (100 mg, 0.432 mmol) and 1H-pyrazol-3- ylboronic acid (48.3 mg, 0.432 mmol, 1.00 eq.) in dioxane/water (8:3, 5.00 mL) was added Pd(dppf)Cl2 (31.6 mg, 0.0432 mmol, 0.100 eq.) and potassium carbonate (179 mg, 1.30 mmol, 3.00 eq.). The mixture was stirred at 80 °C for 16 hours under nitrogen atmosphere. The mixture was cooled down, diluted with water, and extracted with dichloromethane/MeOH (v/v = 10:1) and the combined organic layers were concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to obtain the desired target, which was further purified by trituration with acetonitrile to afford 3-chloro-6-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridine as an off-white powder. 1H NMR (400 MHz, DMSO-d6, ppm) δ =13.07 (s, 1H), 8.65 (s, 1H), 7.86 (d, 2H), 7.69 (d, 2H), 6.94 (d, 1H). Step 2: Preparation of 6-(4-bromo-1H-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine
Figure imgf000157_0002
To a solution of ethyl 3-chloro-6-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridine (400 mg, 1.83 mmol) in dimethylformamide (5.00 mL) was added 1-bromopyrrolidine-2,5-dione (326 mg, 1.83 mmol, 1.00 eq.). The mixture was stirred under reflux for 1 hour, cooled down to room temperature, and then slowly poured into water. The resulting suspension was filtered and the solid was purified over a C18 cartridge. The desired fractions were lyophilized to afford 6-(4-bromo-1H-pyrazol-3-yl)-3-chloro-imidazo[1,2- a]pyridine as a brown solid. LC/MS (method A) retention time = 0.74 min; [M+H]+ = 298.8 Step 3: Preparation of 3-chloro-6-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]imidazo[1,2-a]pyridine To a mixture of (4-fluorophenyl)boronic acid (141 mg, 1.01 mmol, 1.20 eq.) and 6-(4-bromo-1H-pyrazol- 3-yl)-3-chloro-imidazo[1,2-a]pyridine (250 mg, 0.840 mmol) in dioxane/water (v/v = 4:1, 3.00 mL) was added [1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (61.5 mg, 0.0840 mmol, 0.100 eq.) and potassium carbonate (348 mg, 2.52 mmol, 3.00 eq.). The mixture was stirred at 80 °C for 16 hours under nitrogen atmosphere, and then cooled down to room temperature, diluted with water, and extracted with dichloromethane/MeOH (v/v = 10:1). The combined organic layers were concentrated under reduced pressure and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 3-chloro-6-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]imidazo[1,2- a]pyridine as a white solid. LC/MS (method A) retention time = 0.86 min; [M+H]+ = 312.9 Step 4: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 65) A mixture of 3-chloro-6-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]imidazo[1,2-a]pyridine (30.0 mg, 0.0959 mmol, 1.00 eq.) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (32.0 mg, 0.115 mmol, 1.20 eq.) were dissolved in pre-mixed dioxane/water (v/v= 4:1, 2.00 mL). Pd(dppf)Cl2 (7 mg, 0.01 mmol, 0.10 eq.) and potassium carbonate (40 mg, 0.29 mmol, 3.0 eq.) were added and the mixture was heated at 80 °C for 2 hours under nitrogen atmosphere. The reaction mixture was cooled down, diluted with water, and extracted with dichloromethane. The combined organic layers were concentrated under reduced pressure and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford the desired target, which was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid. LC/MS (method A) retention time = 0.88 min; [M+H]+ = 429 1H NMR (400 MHz, DMSO-d6, ppm) δ = 12.99 (br s, 1H), 9.96 (br s, 1H), 8.35-8.19 (m, 2H), 7.90-7.79 (m, 2H), 7.76-7.55 (m, 3H), 7.51-7.30 (m, 3H), 7.13 (t, J = 8.8 Hz, 2H), 3.74 (s, 3H). Example 3: preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 19) (Compound 19) Step 1: Preparation of (4-bromo-2,5-dimethyl-pyrazol-3-yl) trifluoromethanesulfonate
Figure imgf000159_0001
To a solution of 2,5-dimethyl-4H-pyrazol-3-one (3.00 g, 26.8 mmol) in dichloromethane (50.0 mL) was added 1-bromopyrrolidine-2,5-dione (5.00 g, 28.1 mmol, 1.05 eq.) at 0 °C. The reaction mixture was stirred at 0 °C for 30 minutes, after which 2,6-dimethylpyridine (6.23 mL, 53.5 mmol, 2.00 eq.) and trifluoromethanesulfonic anhydride (5.40 mL, 32.1 mmol, 1.20 eq.) were added. The reaction mixture was stirred at 0 °C for 1 hour, and then it was diluted with a NaHCO3 solution, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford (4-bromo-2,5-dimethyl-pyrazol- 3-yl) trifluoromethanesulfonate as a clear oil. LC/MS (method A) retention time = 1.48 min; [M+H]+ = 323.1 Step 2: Preparation of 4-bromo-5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazol
Figure imgf000159_0002
To a stirred solution of (4-bromo-2,5-dimethyl-pyrazol-3-yl) trifluoromethanesulfonate (500 mg, 1.55 mmol) in toluene (30.0 mL) was added (4-fluoro-3-methoxy-phenyl)boronic acid (395 mg, 2.32 mmol, 1.50 eq.), potassium phosphate (985 mg, 4.64 mmol, 3.00 eq.) and Pd(PPh3)4 (358 mg, 0.310 mmol, 0.200 eq.) under a nitrogen atmosphere. The mixture was heated at 100 °C and stirred for 4 hours, then it was diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 4- bromo-5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazol as a yellow solid. LC/MS (method A) retention time = 1.33 min; [M+H]+ = 301.1 Step 3: Preparation of 3-chloro-6-[5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazol-4-yl]imidazo[1,2- a]pyridine
Figure imgf000160_0001
To a stirred solution of 4-bromo-5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazole (250 mg, 0.836 mmol) in pre-mixed dioxane/water (v/v = 5:1, 5.00 mL) was added potassium carbonate (289 mg, 2.09 mmol, 2.50 eq.) and Pd(dppf)Cl2 (61 mg, 0.084 mmol, 0.10 eq.) under nitrogen atmosphere. The reaction mixture was stirred at 80 °C for 4 hours, after which it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 3-chloro-6-[5-(4-fluoro-3-methoxy-phenyl)-1,3- dimethyl-pyrazol-4-yl]imidazo[1,2-a]pyridine as a brown oil. LC/MS (method A) retention time = 1.10 min; [M+H]+ = 371.2 Step 4: Preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 19) A mixture of 3-chloro-6-[5-(4-fluoro-3-methoxy-phenyl)-1,3-dimethyl-pyrazol-4-yl]imidazo[1,2-a]pyridine (180 mg, 0.485 mmol, 1.00 eq.) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2- pyridyl]carbamate (203 mg, 0.728 mmol, 1.50 eq.) were dissolved in pre-mixed dioxane/water (v/v= 4:1, 5.00 mL). Brettphos Pd G3 (CAS: 1470372-59-8, 44.0 mg, 0.0485 mmol, 0.10 eq.) and potassium carbonate (168 mg, 1.21 mmol, 2.50 eq.) were added under nitrogen and the mixture was heated at 100 °C and stirred for 3 hours. The reaction mixture was then cooled down, diluted with water, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to obtain the desired target, which was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,3- dimethyl-pyrazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a white solid. LC/MS (method A) retention time = 0.93 min; [M+H]+ = 487 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.41 (s, 1H), 8.41 (d, J = 2.0 Hz, 1H), 8.05 (s, 1H), 7.94 (d, J = 8.6 Hz, 1H), 7.76 (s, 1H), 7.69 (dd, J = 8.6, 2.4 Hz, 1H), 7.60 (d, J = 9.2 Hz, 1H), 7.28 - 7.19 (m, 2H), 7.09 (dd, J = 9.2, 1.4 Hz, 1H), 6.84 (m, 1H), 3.73 (2 x s, 6H), 3.68 (s, 3H), 2.25 (s, 3H). Example 4: preparation of methyl N-[5-[6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 38) (Compound 38) Step 1: Preparation of 2-chloro-5-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]pyridine
Figure imgf000161_0001
A solution of 4-fluorobenzamide (2.80 g, 20.1 mmol) in 1,1-dimethoxy-N,N-dimethyl-methanamine (14.0 mL) was heated at 100 °C for 2 h. The resulting reaction mixture was cooled to room temperature and concentrated under reduced pressure. Acetic acid (28.0 mL) and (6-chloro-3-pyridyl)hydrazine (2.89 g, 20.1 mmol, 1.0 eq.) were added to the crude residue, and the resulting mixture was heated at 95 °C for 2 hours. The mixture was then cooled and adjusted to pH 7 with aq. NaHCO3, diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 2-chloro-5-[5-(4-fluorophenyl)- 1,2,4-triazol-1-yl]pyridine as a yellow solid. LC/MS (method A) retention time = 1.15 min; [M+H]+ = 275.1 Step 2: Preparation of N-(2,2-dimethoxyethyl)-5-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]pyridin-2-amine
Figure imgf000161_0002
To a stirred solution of 2-chloro-5-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]pyridine (50.0 mg, 182 mmol) in toluene (2.00 mL) was added 2,2-dimethoxyethanamine (21.1 mg, 0.200 mmol, 1.10 eq.), Pd2(dba)3 (8.3 mg, 0.0091 mmol, 0.05 eq.), BINAP (5.7 mg, 0.0091 mmol, 0.050 eq.) and sodium tert-butoxide (44 mg, 0.46 mmol, 2.5 eq.) under nitrogen atmosphere. The reaction mixture was stirred at 80 °C for 4 hours, after which it was diluted with water and extracted with dichloromethane. The combined organic phases were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford N-(2,2-dimethoxyethyl)-5-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]pyridin-2-amine as a yellow oil. LC/MS (method A) retention time = 0.98 min; [M+H]+ = 344.3 Step 3: Preparation of 6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridine
Figure imgf000162_0001
A solution of N-(2,2-dimethoxyethyl)-5-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]pyridin-2-amine (200 mg, 0.582 mmol) in dichloroethane/TfOH (v/v = 5:1, 12.0 mL) was stirred at 80 °C for 3 hours. The resulting mixture was concentrated under reduced pressure and the resulting crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 6-[5-(4-fluorophenyl)-1,2,4-triazol-1- yl]imidazo[1,2-a]pyridine as a yellow oil. LC/MS (method A) retention time = 0.68 min; [M+H]+ = 280.2 Step 4: Preparation of 6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]-3-iodo-imidazo[1,2-a]pyridine
Figure imgf000162_0002
To a solution of 6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridine (200 mg, 0.215 mmol) in acetonitrile (2.00 mL) at 0 °C was added 1-iodopyrrolidine-2,5-dione (48 mg, 0.22 mmol, 1.0 eq.) by portions. The resulting solution was slowly warmed to room temperature and stirred for an additional 3 hours. The reaction mixture was then diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]-3-iodo-imidazo[1,2-a]pyridine as a yellow solid. LC/MS (method A) retention time = 1.03 min; [M+H]+ = 406.1 Step 5: Preparation of N-[5-[6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 38) A mixture of 6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]-3-iodo-imidazo[1,2-a]pyridine (50 mg, 0.12 mmol, 1.0 eq.) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (34 mg, 0.12 mmol, 1.0 eq.) were dissolved in a pre-mixed dioxane/water solution (v/v= 5:1, 1.20 mL). Pd(dppf)Cl2 (9.0 mg, 0.012 mmol, 0.10 eq.) and potassium carbonate (43 mg, 0.31 mmol, 2.50 eq.) were added under nitrogen and the mixture was heated at 65 °C and stirred for 3 hours. The mixture was cooled down, diluted with water, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to obtain the desired target, which was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[5- (4-fluorophenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an orange solid. LC/MS (method A) retention time = 0.93 min; [M+H]+ = 430 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.44 (s, 1H), 8.79 (dd, J = 1.8, 0.8 Hz, 1H), 8.48 - 8.42 (m, 1H), 8.28 (s, 1H), 7.95 - 7.87 (m, 3H), 7.78 (dd, J = 9.4, 0.6 Hz, 1H), 7.64 (dd, J = 8.8, 5.4 Hz, 2H), 7.35 - 7.27 (m, 3H), 3.71 (s, 3H). Example 5: preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 57)
Figure imgf000163_0001
(Compound 57) Step 1: Preparation of 3-chloro-6-(2-methylpyrazol-3-yl)imidazo[1,2-a]pyridine
Figure imgf000163_0002
To a mixture of 6-bromo-3-chloro-imidazo [1,2-a]pyridine (1.50 g, 6.48 mmol) and (2-methylpyrazol-3- yl)boronic acid (1.22 g, 9.72 mmol, 1.50 eq.) in a pre-mixed solvent mixture of dioxane/water (v/v = 5:1, 25.0 mL) was added Pd(dppf)Cl2 (474 mg, 0.648 mmol, 0.100 eq.) and potassium carbonate (2.24 g, 16.2 mmol, 2.50 eq.). The reaction mixture was heated to 80°C and stirred for 2 hours under nitrogen atmosphere. The reaction mixture was then cooled and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 3-chloro-6-(2-methylpyrazol-3-yl)imidazo[1,2-a]pyridine as a light yellow solid. LC/MS (method A) retention time = 0.88 min; [M+H]+ = 233.2 Step 2: Preparation of 6-(4-bromo-2-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine
Figure imgf000163_0003
To a stirred mixture of 3-chloro-6-(2-methylpyrazol-3-yl)imidazo[1,2-a]pyridine (620 mg, 2.66 mmol) in dimethylformamide (8.00 mL) at rt was added 1-bromopyrrolidine-2,5-dione (569 mg, 3.20 mmol, 1.20 eq.) portionwise. The reaction mixture was stirred for an additional 2 hours at room temperature, and then it was quenched with water resulting in the formation of a white solid in the aqueous layer. The mixture was filtered, the filter cake was washed with water and the residue was dried under reduced pressure to afford 6-(4-bromo-2-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine as a brown solid. LC/MS (method A) retention time = 1.13 min; [M+H]+ = 313.0 Step 3: Preparation of 3-chloro-6-[4-(4-fluorophenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridine
Figure imgf000164_0001
To a mixture of 6-(4-bromo-2-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine (200 mg, 0.642 mmol) and (4-fluorophenyl)boronic acid (108 mg, 0.770 mmol, 1.20 eq.) in pre-mixed solvent solution of dioxane/water (v/v = 4:1, 5.00 mL) was added Pd(dppf)Cl2 (47 mg, 0.064 mmol) and potassium carbonate (221 mg, 1.60 mmol, 2.50 eq.). The reaction mixture was heated at 80 °C and stirred for 2 hours under a nitrogen atmosphere. The reaction mixture was then concentrated under reduced pressure and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 3-chloro-6-[4-(4-fluorophenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2- a]pyridine as a yellow oil. LC/MS (method A) retention time = 1.25 min; [M+H]+ = 327.2 Step 4: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 57) A mixture of 3-chloro-6-[4-(4-fluorophenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridine (130 mg, 0.398 mmol, 1.00 eq.) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (93.6 mg, 0.477 mmol, 1.20 eq.) were dissolved in pre-mixed solution of dioxane/water (v/v= 4:1, 5.00 mL). [2-(2-aminophenyl)phenyl]-methylsulfonyloxy-palladium;dicyclohexyl-[3,6-dimethoxy-2-(2,4,6- triisopropylphenyl)phenyl]phosphane (36 mg, 0.040 mmol, 0.10 eq.) and potassium carbonate (137 mg, 0.995 mmol, 2.50 eq.) were added under nitrogen and the reaction mixture was heated at 75 °C for 2 hours. The mixture was cooled down and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to obtain the desired compound, which was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[4-(4- fluorophenyl)-2-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white powder. LC/MS (method A) retention time = 1.05 min; [M+H]+ = 443 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 8.59 (s, 1H), 8.50 (d, J = 1.2 Hz, 1H), 8.05 - 7.91 (m, 2H), 7.89 (s, 1H), 7.82 (s, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.27 (dd, J = 8.7, 5.4 Hz, 2H), 7.19 (dd, J = 9.4, 1.4 Hz, 1H), 7.11 (t, J = 8.8 Hz, 2H), 3.78 (s, 3H), 3.70 (s, 3H). Example 6: preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-4- -2-
Figure imgf000165_0001
Step 1: Preparation of 5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazole
Figure imgf000165_0002
To a mixture of 4-bromo-1-fluoro-2-methoxy-benzene (900 mg, 4.39 mmol) and (2-methylpyrazol-3- yl)boronic acid (663 mg, 5.27 mmol, 1.20 eq.) in a pre-mixed solution of dioxane/water (v/v = 4:1, 18.0 mL) was added Pd(dppf)Cl2 (319 mg, 0.439 mmol, 0.100 eq.) and potassium carbonate (1.82 g, 13.2 mmol, 3.00 eq.). The reaction mixture was heated at 80 °C and stirred for 2 hours under a nitrogen atmosphere. The reaction mixture was then cooled, diluted with water and extracted with dichloromethane. The combined organic layers were concentrated under reduced pressure and the crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford the desired target which was further purified by trituration with acetonitrile to afford 5-(4-fluoro-3- methoxy-phenyl)-1-methyl-pyrazole as a colorless oil. LC/MS (method A) retention time = 1.03 min; [M+H]+ = 207.1 Step 2: Preparation of 4-bromo-5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazole
Figure imgf000165_0003
To a solution of 5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazole (400 mg, 1.94 mmol) in dimethylformamide (5.00 mL) was added 1-bromopyrrolidine-2,5-dione (518 mg, 2.91 mmol, 1.50 eq.). The reaction mixture was stirred at room temperature for 1 hour, after which it was diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 4-bromo-5-(4-fluoro-3- methoxy-phenyl)-1-methyl-pyrazole as a light yellow solid. LC/MS (method A) retention time = 1.22 min; [M+H]+ = 284.9 Step 3: Preparation of 3-chloro-6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-4-yl]imidazo[1,2- a]pyridine
Figure imgf000166_0001
To a mixture of 4-bromo-5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazole (400 mg, 1.40 mmol) and (3- chloroimidazo[1,2-a]pyridin-6-yl)boronic acid (331 mg, 1.68 mmol, 1.20 eq.) in a pre-mixed solution of dioxane/water (v/v = 4:1, 5.00 mL) was added Pd(dppf)Cl2 (102 mg, 0.140 mmol, 0.100 eq.) and potassium carbonate (582 mg, 4.21 mmol, 3.00 eq.). The reaction mixture was heated at 80 °C and stirred for 2 hours under nitrogen atmosphere. The reaction mixture was then cooled, diluted with water, and extracted with dichloromethane/MeOH (v/v = 10:1). The combined organic layers were concentrated under reduced pressure and the resulting residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford the desired target, which was further purified by trituration with acetonitrile to ultimately afford 3-chloro-6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-4- yl]imidazo[1,2-a]pyridine as a white solid. LC/MS (method A) retention time = 0.91 min; [M+H]+ = 357 Step 4: Preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-4-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 20) A mixture of 3-chloro-6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-4-yl]imidazo[1,2-a]pyridine (200 mg, 0.561 mmol, 1.00 eq.) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2- pyridyl]carbamate (187 mg, 0.673 mmol, 1.20 eq.) was dissolved in a pre-mixed solution of dioxane/water (v/v= 4:1, 5.00 mL). Brettphos Pd G3 (CAS 1470372-59-8, 51 mg, 0.056 mmol, 0.10 eq.) and potassium carbonate (232 mg, 1.68 mmol, 3.00 eq.) were added and the mixture was heated at 80 °C under an atmosphere of nitrogen for 2 hours. The reaction mixture was cooled down, diluted with water, and extracted with dichloromethane/methanol (v/v = 10:1). The combined organic layers were concentrated under reduced pressure and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford the desired target, which was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a white solid. LC/MS (method A) retention time = 0.90 min; [M+H]+ = 473 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.38 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 8.03 (s, 1H), 7.94 (m, 2H), 7.72 (s, 1H), 7.67 (dd, J = 8.7, 2.4 Hz, 1H), 7.61 (d, J = 9.4 Hz, 1H), 7.28 (m, 3H), 6.94 (ddd, J = 8.1, 4.2, 1.8 Hz, 1H), 3.77 (s, 3H), 3.74 (s, 3H), 3.71 (s, 3H). Example 7: preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-oxo-1,2,4-oxadiazol- 3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 32) N
Figure imgf000167_0001
(Compound 32) Step 1: Preparation of N-hydroxyimidazo[1,2-a]pyridine-6-carboxamidine
Figure imgf000167_0002
To the mixture of imidazo[1,2-a]pyridine-6-carbonitrile (3.00 g, 21.0 mmol) in MeOH (30 mL) was added formylperoxysodium (7.04 g, 83.8 mmol, 4.00 equ.) and hydroxylamine hydrochloride (2.91 g, 41.9 mmol, 2.00 eq.), and the resulting mixture was heated at 75 °C and stirred for 6 hours. The reaction mixture was then cooled, filtered off and the filtrate evaporated to dryness to afford a crude residue that was further purified by washing with water. Drying of the solid in vacuo afforded N-hydroxyimidazo[1,2- a]pyridine-6-carboxamidine as a brown solid. LCMS (method A): retention time = 0.18 min; [M+H]+ = 177.2 Step 2: Preparation of 3-imidazo[1,2-a]pyridin-6-yl-4H-1,2,4-oxadiazol-5-one
Figure imgf000167_0003
To a stirred solution of N-hydroxyimidazo[1,2-a]pyridine-6-carboxamidine (3.25 g, 18.4 mmol) in pyridine (150 mL) at 0 °C was added dropwise ethyl carbonochloridate (2.20 g, 20.3 mmol, 1.10 eq.). The mixture was stirred at room temperature for 15 min, and then the resulting mixture was heated at 95 °C and stirred for an additional 2 hours. The reaction mixture was then cooled and concentrated under reduced pressure to remove the pyridine. The cooled reaction mixture was then washed with tert-butyl methyl ether to obtain a crude residue that was further purified by washing with water. Drying the resulting solid in vacuo afforded 3-imidazo[1,2-a]pyridin-6-yl-4H-1,2,4-oxadiazol-5-one as a brown solid. LCMS (method A) retention time = 0.28 min; [M+H]+ = 203.2 Step 3: Preparation of 3-(3-iodoimidazo[1,2-a]pyridin-6-yl)-4H-1,2,4-oxadiazol-5-one To a stirred mixture of 3-imidazo[1,2-a]pyridin-6-yl-4H-1,2,4-oxadiazol-5-one (0.400 g, 1.98 mmol) in N, N-dimethylformamide (50 mL) was added portionwise 1-iodopyrrolidine-2,5-dione (0.467 g, 2.08 mmol, 1.05 eq.) at 16 °C. The resulting mixture was warmed to room temperature and stirred for an additional 2 hours. The reaction was then diluted with water and concentrated under reduced pressure. The resulting residue was extracted with dichloromethane to afford 3-(3-iodoimidazo[1,2-a]pyridin-6-yl)-4H- 1,2,4-oxadiazol-5-one as a light yellow solid. LCMS (method A) retention time = 0.84 min; [M+H]+ = 329.1 Step 4: Preparation of (4-fluoro-3-methoxy-phenyl)-(2,4,6-trimethylphenyl) iodonium; trifluoromethanesulfonate
Figure imgf000168_0001
To a stirred mixture of 1-fluoro-4-iodo-2-methoxy-benzene methane (3.00 g, 11.2 mmol), oxone (6.88 g, 11.2 mmol) and mesitylene (2.69 g, 22.4 mmol, 2.00 eq.) in acetonitrile (24.0 mL) at room temperature was added H2SO4 (4.80 mL). The reaction mixture was stirred overnight and then a solution of triflic acid (6.72 g, 22.4 mmol, 2.00 eq.) in water (18.0 mL) was added dropwise. After completion, the diaryliodonium salt was extracted with dichloromethane. The combined organic layers were dried with sodium sulfate and the solvent was removed under reduced pressure. Then a mixture of hexane and diethyl ether was added to the residue. The product was filtered off and washed with hexane to afford the desired product, which was dried under vacuo to afford (4-fluoro-3-methoxy-phenyl)-(2,4,6- trimethylphenyl) iodonium trifluoromethanesulfonate as a brown solid. LC/MS (method A) retention time = 1.04 min; [M+H]+ = 371 Step 5: Preparation of 4-(4-fluoro-3-methoxy-phenyl)-3-(3-iodoimidazo[1,2-a]pyridin-6-yl)-1,2,4- oxadiazol-5-one
Figure imgf000168_0002
To the solution of triethylamine (361 mg, 3.57 mmol, 2.60 eq.), 3-(3-iodoimidazo[1,2-a] pyridin-6-yl)- 4H- 1,2,4- oxadiazol-5-one (450 mg, 1.37 mmol) and (4-fluoro-3-methoxy-phenyl)-(2,4,6- trimethylphenyl)iodonium; trifluoromethanesulfonate (1.86 g, 3.57 mmol, 2.6 eq.) in dichloroethane (80.0 mL) was added CuI (261 mg, 1.37 mmol, 1.00 eq.) under argon atmosphere. The resulted mixture was heated at 60 °C for 24 hours. After completion, the mixture was quenched with water and diluted with dichloromethane/MeOH. The resulting mixture was filtered, and the filtrate was concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 4-(4-fluoro-3-methoxy-phenyl)-3-(3-iodoimidazo [1,2-a] pyridin-6-yl)- 1,2,4-oxadiazol-5-one as a sticky oil. LC/MS (method A) retention time = 1.10 min; [M+H]+ = 453 Step 6: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-oxo-1,2,4-oxadiazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 32) To a mixture of 4-(4-fluoro-3-methoxy-phenyl)-3-(3-iodoimidazo[1,2-a]pyridin-6-yl)-1,2,4- oxadiazol-5- one (110.0 mg, 0.243 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2-yl)-2- pyridyl]carbamate (81.2 mg, 0.292 mmol, 1.20 eq.) in a pre-mixed solvent solution of dioxane/water (v/v = 4:1, 7.00 mL) was added Pd(dppf)Cl2 (18 mg, 0.024 mmol, 0.10 eq.) and potassium carbonate (85 mg, 0.61 mmol, 2.50 eq.). The reaction mixture was heated at 45 °C and stirred for 1 hour under an atmosphere of nitrogen. The reaction mixture was then concentrated under reduced pressure, and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to give the desired compound, which was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[4- (4-fluoro-3-methoxy- phenyl)-5-oxo-1,2,4-oxadiazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white powder. LC/MS (method A) retention time = 1.05 min; [M+H]+ = 477 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.46 (s, 1H), 8.42 (d, J = 2.2 Hz, 1H), 8.38 (s, 1H), 7.98 (d, J = 8.6 Hz, 1H), 7.88 (s, 1H), 7.76 (d, J = 2.8 Hz, 1H), 7.74 (d, J = 2.4 Hz, 1H), 7.51 (dd, J = 7.8, 2.4Hz, 1H), 7.36 - 7.25 (m, 2H), 7.11 (dt, J = 6.4, 3.8 Hz, 1H), 3.74 (app s, 6H). Example 8: preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 47)
Figure imgf000169_0001
(Compound 47) Step 1: Preparation of 6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-a]pyridine To a mixture of 2-(4-fluorophenyl)pyrrolidine (201 mg, 1.22 mmol, 1.2 eq.) and 6-bromoimidazo[1,2- a]pyridine (200 mg, 1.02 mmol) in toluene (5.00 mL) was added Pd2(dba)3 (96 mg, 0.10 mmol, 0.10 eq.), XPhos (25 mg, 0.051 mmol, 0.05 eq.) and sodium tert-butoxide (199 mg, 2.03 mmol, 2.00 eq.). The resulting solution was heated to 110 °C and stirred overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate and extracted with an aqueous solution of NaHCO3. The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (cyclohexane/ethyl acetate) to afford 6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-a]pyridine. LC/MS (Method E) retention time = 0.78 min; [M+H]+ = 282 Step 2: Preparation of 6-[2-(4-fluorophenyl)pyrrolidin-1-yl]-3-iodo-imidazo[1,2-a]pyridine
Figure imgf000170_0001
To a stirred solution of 6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-a]pyridine (140 mg, 0.463 mmol) in dimethylformamide (2.00 mL) at 0 °C was added N-iodosuccinimide (130 mg, 0.579 mmol, 1.25 eq.). The resulting reaction mixture was stirred at room temperature for 2 hours, after which it was poured into water (20.0 mL) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[2-(4- fluorophenyl)pyrrolidin-1-yl]-3-iodo-imidazo[1,2-a]pyridine as a brown solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 7.51 (s, 1H), 7.42 (d, J = 9.6 Hz, 1H), 7.34 - 7.31 (m, 2H), 7.15 (t, J = 8.8 Hz, 2H), 7.09 (d, J = 1.6 Hz, 1H), 6.89 (dd, J = 9.6, 2.0 Hz, 1H), 4.81 (dd, J = 8.0, 3.2 Hz, 1H), 3.80 - 3.75 (m, 1H), 3.42 - 3.35 (m, 1H), 2.46 - 2.39 (m, 1H), 2.01 (t, J = 8.8 Hz, 2H), 1.84 - 1.78 (m, 1H). Step 3: Preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 47) A mixture of 6-[2-(4-fluorophenyl)pyrrolidin-1-yl]-3-iodo-imidazo[1,2-a]pyridine (140 mg, 0.275 mmol, 1.00 eq.) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (94 mg, 0.33 mmol, 1.2 eq.) were dissolved in pre-mixed solution of dioxane/water (v/v= 3:1, 5.00 mL). Potassium carbonate (76 mg, 0.55 mmol, 2.0 eq.) was added and the reaction mixture was degassed with argon for 5 minutes. CataCXium® A Pd G3 (CAS 1651823-59-4, 10 mg, 0.014 mmol, 0.05 mmol) was added and the mixture was heated at 100°C for 1 hour under microwave irraditation. The mixture was cooled down, filtered through a pad of celite and washed with ethyl acetate. The filtrate was washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford methyl N-[5-[6-[5-(4-fluorophenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as dark green solid. LC/MS (Method E) retention time = 3.85 min; [M+H]+ = 432 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 8.38 (s, 1H), 7.91 (d, 1H), 7.70 (m, 1H), 7.60 (s, 1H), 7.49 (d, 1H), 7.28 (m, 3H), 7.13 (m, 2H), 6.92 (m, 1H), 4.71 (m, 1H), 3.72 (m, 4H), 3.32 (m, 1H), 2.40 (m, 1H), 1.99 (m, 2 H), 1.79 (m, 1H). Example 9: preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4- oxadiazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 10)
Figure imgf000171_0001
(Compound 10) Step 1: Preparation of 2-chloro-N-(-4-fluoro-3-methoxy-phenyl)acetamide
Figure imgf000171_0002
To a suspension of 4-fluoro-3-methoxy-aniline (10.0 g, 70.9 mmol) and potassium carbonate (10.8 g, 77.9 mmol, 1.10 eq.) in dimethylformamide (50.0 mL) at 0 °C was added, dropwise, a solution of 2- chloroacetyl chloride (8.80 g, 77.9 mmol, 1.00 eq.) in dimethylformamide (5.00 mL). The reaction mixture was stirred at room temperature for 3 hours, then it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford 2-chloro-N-(4-fluoro-3-methoxy- phenyl)acetamide as a colorless oil. LC/MS (method A) retention time = 1.03 min; [M+H]+ = 218.1 Step 2: Preparation of N-(2-chloroethyl)-4-fluoro-3-methoxy-aniline
Figure imgf000171_0003
To a solution of 2-chloro-N-(4-fluoro-3-methoxy-phenyl)acetamide (10.0 g, 46.0 mmol) in THF (120 mL) at 0°C was added, dropwise, BH3-THF (1.00 mol/L, 68.9 mL, 68.9 mmol, 1.50 eq.). The reaction mixture was warmed to room temperature and stirred for an additional 3 hours, after which it was poured into ice water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford N-(2-chloroethyl)-4- fluoro-3-methoxy-aniline as a colorless liquid. LC/MS (method A) retention time = 1.23 min; [M+H]+ = 204.2 Step 3: Preparation of N-[2-(benzhydrylideneamino)oxyethyl]-4-fluoro-3-methoxy-aniline
Figure imgf000172_0001
To a stirred suspension of diphenylmethanone oxime (8.14 g, 41.2 mmol, 1.20 eq.) in DMSO (40.0 mL) at room temperature was added potassium hydroxide (9.64 g, 172 mmol, 5.00 eq.). The reaction mixture was stirred for 3 minutes, then a solution of N-(2-chloroethyl)-4-fluoro-3-methoxy-aniline (7.00 g, 34.4 mmol, 1.00 eq.) in DMSO (10.0 mL) was added dropwise. The reaction mixture was stirred at room temperature for 2 hours, then it was poured into ice water. The aqueous layer was extracted with dichloromethane, the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford N-[2- (benzhydrylideneamino)oxyethyl]-4-fluoro-3-methoxy-aniline as a viscous oil. LC/MS (method A) retention time = 1.63 min; [M+H]+ = 365.2 Step 4: Preparation of O-[2-(4-fluoro-3-methoxy-anilino)ethyl]hydroxylamine
Figure imgf000172_0002
A solution of N-[2-(benzhydrylideneamino)oxyethyl]-4-fluoro-3-methoxy-aniline (5.20 g, 15.6 mmol) in 6M HCl (25.9 mL, 156 mmol) and dioxane (10.0 mL) was refluxed under nitrogen for 8 hours. The resulting mixture was extracted with dichloromethane. The aqueous solution was then adjusted to pH 9 with solid NaHCO3 and extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford O-[2-(4-fluoro-3-methoxy-anilino)ethyl]hydroxylamine as a light yellow liquid. LC/MS (method A) retention time = 0.66 min; [M+H]+ = 201.1 Step 5: Preparation of ethyl 3-bromoimidazo[1,2-a]pyridine-6-carboximidate To a solution of 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile (3.00 g, 13.5 mmol) in ethanol/dichloromethane (v/v=1/4, 200 mL,) at 0 °C was added sodium ethanethiolate (0.568 g, 6.76 mmol). The reaction mixture was then warmed to room temperature and stirred for an additional 16 hours. The reaction mixture was concentrated to dryness under reduced pressure and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford ethyl 3- bromoimidazo[1,2-a]pyridine-6-carboximidate as white solid. LC/MS (method A) retention time = 0.75; [M+H]+ = 270.0 Step 6: Preparation of 3-(3-bromoimidazo[1,2-a]pyridin-6-yl)-4-(4-fluoro-3-methoxy-phenyl)-5,6- dihydro-1,2,4-oxadiazine
Figure imgf000173_0001
To a stirred solution of ethyl 3-bromoimidazo[1,2-a]pyridine-6-carboximidate (700 mg, 2.61 mmol) in acetic acid (25.0 mL) was added O-[2-(4-fluoro-3-methoxy-anilino)ethyl]hydroxylamine (549 mg, 2.74 mmol, 1.05 eq.) portion wise at 23 °C. The solution was stirred at room temperature for 4 hours, then stirred at 90 °C for another 10 hours. After completion, the resulting mixture was quenched with water (10.0 mL), concentrated and the residual was extracted with dichloromethane/MeOH (20.0 mL x 3, v/v=10:1). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, concentrated by reduced pressure and purified over silica gel cartridge (dichloromethane/methanol) to afford 3-(3-bromoimidazo[1,2-a]pyridin-6-yl)-4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4- oxadiazine as a brown solid. LC/MS (method A) retention time = 1.08 min; [M+H]+ = 407.0 Step 7: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4-oxadiazin-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 10) To a stirred mixture of 3-(3-bromoimidazo[1,2-a]pyridin-6-yl)-4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro- 1,2,4-oxadiazine (300 mg, 0.740 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 2-pyridyl]carbamate (216 mg, 0.777 mmol, 1.05 eq.) in pre-mixed solution of dioxane/water (v/v = 5:1, 6.00 mL) was added Pd(dppf)Cl2 (54.2 mg, 0.074 mmol, 0.100 eq.) and potassium carbonate (256 mg, 1.85 mmol, 2.50 eq.). The mixture was stirred at 45 °C for 1 hour under atmosphere of nitrogen, then it was concentrated under reduced pressure and the residue was diluted with brine (10.0 mL) and extracted with dichloromethane/MeOH (30.0 mL x 3, v/v = 10:1). The combined organic layers were concentrated under reduced pressure. The residual was purified by silica gel column chromatography (eluting with dichloromethane/MeOH) to obtain desired compound, which was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4- oxadiazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a white powder. LC/MS (method A) retention time = 0.95 min; [M+H]+ = 477.2 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.47 (s, 1H), 8.43 (d, J = 1.6 Hz, 2H), 8.01 (d, J = 8.6 Hz, 1H), 7.81 (dd, J = 8.6, 2.4 Hz, 1H), 7.78 (s, 1H), 7.51 (d, J = 9.4 Hz, 1H), 7.15 (dd, J = 9.4, 1.6 Hz, 1H), 7.10 (dd, J = 7.8, 2.4 Hz, 1H), 7.03 (dd, J = 11.4, 8.8Hz, 1H), 6.73 - 6.47 (m, 1H), 4.16 (t, J = 4.4 Hz, 2H), 3.82 (t, J = 4.4 Hz, 2H), 3.73 (s, 3H), 3.71 (s, 3H). Example 10: preparation of methyl N-[5-[6-[5-(4-fluorophenyl)-1-methyl-imidazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 23)
Figure imgf000174_0001
(Compound 23) Step 1: Preparation of 5-(4-fluorophenyl)-1-methyl-imidazole
Figure imgf000174_0002
To a solution of 1-bromo-4-fluoro-benzene (639 mg, 3.65 mmol, 1.50 eq.) and 1-methylimidazole (200 mg, 2.44 mmol, 1.00 eq.) in dry dimethylformamide (12.0 mL) was added tris(2-furyl)phosphane (57 mg, 0.24 mmol, 0.10 eq.), Pd(OAc)2 (27 mg, 0.12 mmol, 0.05 eq.) and potassium carbonate (673 mg, 4.87 mmol, 2.00 eq.). The reaction mixture was heated to 110 °C and stirred under a nitrogen atmosphere until full conversion. The reaction mixture was then cooled, diluted with ethyl acetate/dichloromethane (25.0 mL, 1:1), filtered, and the filtrate was concentrated under reduced pressure. The crude residue was purified by reverse phase chromatography (eluting with acetonitrile/water, from 10% to 90% containing 0.1% formic acid) to afford 5-(4-fluorophenyl)-1-methyl-imidazole as a white solid. LC/MS (method A) retention time = 0.55 min; [M+H]+ = 177.2 1H NMR (400 MHz, DMSO-d6, ppm) δ = 7.71 (s, 1H), 7.59 - 7.44 (m, 2H), 7.38 - 7.21 (m, 2H), 7.04 (d, J = 0.8 Hz, 1H), 3.66 (s, 3H). Step 2: Preparation of 4-bromo-5-(4-fluorophenyl)-1-methyl-imidazole To a stirred solution of 5-(4-fluorophenyl)-1-methyl-imidazole (320 mg, 1.82 mmol) in acetonitrile (4.00 mL) at 0 °C was added, portionwise, 1-bromopyrrolidine-2,5-dione (323 mg, 1.82 mmol, 1.00 eq.). The resulting solution was slowly warmed to room temperature and stirred for 16 hours. After the transformation was completed, the resulting mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure, and purified by purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 4-bromo-5-(4-fluorophenyl)-1-methyl-imidazole as a white solid. LC/MS (method A) retention time = 1.13 min; [M+H]+ = 257.1 1H NMR (400 MHz, DMSO-d6, ppm) δ = 7.77 (s, 1H), 7.53 (dd, J = 8.8, 5.4 Hz, 2H), 7.35 (t, J = 8.8 Hz, 2H), 3.56 (s, 3H). Step 3: Preparation of methyl N-[5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-pyridyl]carbamate
Figure imgf000175_0001
To a solution of 6-bromo-3-iodo-imidazo[1,2-a]pyridine (4.00 g, 12.4 mmol) in dioxane/water (5/1; 42.0 mL) was added methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (4.13 g, 14.9 mmol), sodium carbonate (2.63 g, 24.8 mmol) and palladium tetrakistriphenylphosphine (1.43 g, 1.24 mmol) under an atmosphere of nitrogen . The reaction mixture was heated at 80 °C and stirred for 16 hours. The The resulting mixture was then cooled and triturated in water, and filtered to provide methyl N-[5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-pyridyl]carbamate as a yellow solid. LCMS (method A) retention time = 0.64 min; [M+H]+ = 347 & 349 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 8.65 (s, 1H), 8.54 (d, J = 1.8 Hz, 1H), 8.12 (dd, J = 8.7, 2.5 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.82 (s, 1H), 7.65 (d, J = 9.4 Hz, 1H), 7.42 (dd, J = 9.6, 1.6 Hz, 1H), 3.72 (s, 3H). Step 4: Preparation of [3-[6-(methoxycarbonylamino)-3-pyridyl]imidazo[1,2-a]pyridin-6-yl]boronic acid To a solution of methyl N-[5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-pyridyl]carbamate (3.00 g, 8.64 mmol) in dioxane (45.0 mL) was added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-1,3,2-dioxaborolane (3.29 g, 13.0 mmol), potassium acetate (1.70 g, 17.3 mmol), and Pd(dppf)Cl2 (0.316 g, 0.432 mmol) under an atmosphere of nitrogen . The reaction mixture was heated to 80 °C and stirred for 16 hours. The mixture was then cooled, washed with water, and the precipitate was collected by filtration, washed with petroleum ether and lyophilized to afford [3-[6-(methoxycarbonylamino)-3- pyridyl]imidazo[1,2-a]pyridin-6-yl]boronic acid which was used directly in next step without further purification. LCMS (method A) retention time = 0.63 min; [M+H]+ = 313.2 Step 5: Preparation of methyl N-[5-[6-[5-(4-fluorophenyl)-1-methyl-imidazol-4-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 23) To a stirred solution of 4-bromo-5-(4-fluorophenyl)-1-methyl-imidazole (250 mg, 0.980 mmol) in a pre- mixed solution of dioxane/water (3.00 mL, v/v = 5/1) was added [3-[6-(methoxycarbonylamino)-3- pyridyl]imidazo[1,2-a]pyridin-6-yl]boronic acid (crude from previous step; 306 mg, 0.980 mmol, 1.00 eq.), potassium carbonate (339 mg, 2.45 mmol, 2.50 eq.) and Pd(dppf)Cl2 (72 mg, 0.098 mmol, 0.10 eq.) and the flask was put under an atmosphere of nitrogen. The mixture was heated to 80 °C and stirred for 6 hours. The reaction mixture was then cooled, diluted with water, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduce pressure, and purified by flash chromatography over silica gel (dichloromethane/MeOH) to obtain the desired target, which was triturated which acetonitrile to afford methyl N-[5-[6-[5-(4-fluorophenyl)-1-methyl-imidazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate as an off-white solid. LC/MS (method A) retention time = 0.89 min; [M+H]+ = 443.3 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.41 (s, 1H), 8.36 (d, J = 1.6 Hz, 1H), 8.15 (s, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.84 (s, 1H), 7.71 (s, 1H), 7.66 - 7.57 (m, 2H), 7.52 - 7.42 (m, 3H), 7.33 (t, J = 8.6 Hz, 2H), 3.74 (s, 3H), 3.46 (s, 3H). Example 11: preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)oxazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 21) (Compound 21) Step 1: Preparation of 5-(4-fluoro-3-methoxy-phenyl)oxazole
Figure imgf000177_0001
To a solution of 1-(isocyanomethylsulfonyl)-4-methyl-benzene (5.00 g, 25.6 mmol) in MeOH (50.0 mL) was added 4-fluoro-3-methoxy-benzaldehyde (5.92 g, 38.4 mmol, 1.50 eq.) and potassium carbonate (8.85 g, 64.0 mmol, 2.50 eq.). The mixture was heated at 75 °C for 3 hours, then it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 5-(4-fluoro-3-methoxy- phenyl)oxazole as a white solid. LC/MS (method A) retention time = 1.18 min; [M+H]+ = 194.2 Step 2: Preparation of 4-bromo-5-(4-fluoro-3-methoxy-phenyl)oxazole
Figure imgf000177_0002
To a solution of 5-(4-fluoro-3-methoxy-phenyl)oxazole (1.00 g, 5.18 mmol) in dry pre-mixed THF/N,N′- Dimethylpropyleneurea (v/v = 1/1, 10.0 mL) at -78 °C under a nitrogen atmosphere, was added, dropwise, n-BuLi (2.5 M in hexane, 8.30 mL, 8.28 mmol, 1.60 eq.). After addition was completed, the solution was stirred at -78 °C for 1 hour. Then 1-bromopyrrolidine-2,5-dione (1.11 g, 6.21 mmol, 1.20 eq.) was added dropwise and the resulting solution was slowly warmed to room temperature and stirred for an additional 2 hours. The final mixture was quenched with water and extracted with diethyl ether. The combined organic phases were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 4-bromo-5-(4-fluoro-3-methoxy-phenyl)oxazole as a white solid. LC/MS (method A) retention time = 1.33 min; [M+H]+ = 274.1 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.60 (s, 1H), 7.57 (m, 1H), 7.39 - 7.47 (m, 2H), 3.92 (s, 3H). Step 3: Preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)oxazol-4-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (Compound 21) To a solution of 4-bromo-5-(4-fluoro-3-methoxy-phenyl)oxazole (250 mg, 0.919 mmol) in dioxane/water (v/v= 5/1, 3.00 mL) was added [3-[6-(methoxycarbonylamino)-3-pyridyl]imidazo[1,2-a]pyridin-6- yl]boronic acid (287 mg, 0.919 mmol, 1.00 eq.), potassium carbonate (317 mg, 2.30 mmol, 2.50 eq.) and Pd(dppf)Cl2 (67.0 mg, 0.092 mmol, 0.100 eq.) and the mixture was put under an atmosphere of nitrogen. The reaction mixture was heated at 80 °C and stirred for 6 hours. The resulting mixture was diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure, purified by flash chromatography over silica gel (dichloromethane/methanol) to give a solid material that was further purified by trituration in acetonitrile to afford methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)oxazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid. LC/MS (method A) retention time = 1.03 min; [M+H]+ = 460.3 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.44 (s, 1H), 8.61 (d, J = 10.6 Hz, 2H), 8.50 (d, J = 1.2 Hz, 1H), 8.01 - 7.95 (m, 2H), 7.85 (s, 1H), 7.74 (d, J = 9.4 Hz, 1H), 7.46 (d, J = 9.4 Hz, 1H), 7.32 - 7.40 (m, 2H), 7.22 (ddd, J = 8.4, 4.2, 2.0 Hz, 1H), 3.79 (s, 3H), 3.72 (s, 3H). Example 12: preparation of methyl N-[5-[6-[5-(4-fluorophenyl)oxazol-4-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 63)
Figure imgf000178_0001
Figure imgf000178_0002
To a solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in MeOH (100 mL) was added 1- (isocyanomethylsulfonyl)-4-methylbenzene (23.6 g, 121 mmol, 1.50 eq.) and potassium carbonate (27.8 g, 201 mmol, 2.50 eq.). The reaction mixture was then heated at 75 °C and stirred for 16 hours, after which it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 5-(4-fluorophenyl)oxazole as a yellow solid. LC/MS (method A) retention time = 1.20 min; [M+H]+ = 164.0 Step 2: Preparation of 4-bromo-5-(4-fluorophenyl)oxazole
Figure imgf000179_0001
To a solution of 5-(4-fluorophenyl)oxazole (2.00 g, 12.3 mmol) in dry THF/ N,N′-Dimethylpropyleneurea (v/v = 1:1, 20.0 mL) at -78 °C under a nitrogen atmosphere was added, dropwise, n-BuLi (2.5 M in hexane, 7.84 mL, 19.61 mmol, 1.60 eq.). After addition, the solution was stirred at -78 °C for 1 hour. Then 1-bromopyrrolidine-2,5-dione (2.62 g, 14.7 mmol, 1.20 eq.) was added dropwise and the resulting solution was slowly warmed to room temperature and stirred for 2 hours. The final mixture was extracted with diethyl ether and sodium chloride/water (2:1) and the combined organic phases were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 4- bromo-5-(4-fluorophenyl)oxazole as a white solid. LC/MS (method A) retention time = 1.33 min; [M+H]+ = 242.1 Step 3: Preparation of methyl N-[5-[6-[5-(4-fluorophenyl)oxazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 63) To a solution of 4-bromo-5-(4-fluorophenyl)oxazole (387 mg, 1.60 mmol) in dioxane/water (v/v= 5/1, 4.80 mL) was added [3-[6-(methoxycarbonylamino)-3-pyridyl]imidazo[1,2-a]pyridin-6-yl]boronic acid (499 mg, 1.60 mmol, 1.00 eq.), potassium carbonate (552 mg, 4.00 mmol, 2.50 eq.) and Pd(dppf)Cl 2 (117.0 mg, 0.160 mmol, 0.100 eq.) under nitrogen. The mixture was heated at 80 °C and stirred for 6 hours. The resulting mixture was cooled to room temperature, diluted with water, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure, and purified by flash chromatography over silica gel (dichloromethane/methanol). The resulting solid was further purified by trituration in acetonitrile to afford methyl N-[5-[6-[5-(4-fluorophenyl)oxazol-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off- white solid. LC/MS (method A) retention time = 0.98 min; [M+H]+ = 430.2 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.43 (s, 1H), 8.59 (s, 1H), 8.56 (s, 1H), 8.49 (d, J = 1.2 Hz, 1H), 7.99 - 7.91 (m, 2H), 7.83 (s, 1H), 7.76 - 7.65 (m, 3H), 7.42 (dd, J = 9.4, 1.6 Hz, 1H), 7.36 (app t, J = 8.8 Hz, 2H), 3.72 (s, 3H). Example 13: preparation of methyl N-[5-[6-[4-(4-fluorophenyl)oxazol-5-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 62) (Compound 62) Step 1: Preparation of 4-(4-fluorophenyl)oxazole
Figure imgf000180_0001
To a solution of 2-bromo-1-(4-fluorophenyl)ethenone (10.0 g, 46.1 mmol) in formic acid (150 mL) at room temperature was added ammonium formate (11.0 g, 175 mmol, 3.80 eq.). The mixture was heated at 110 °C and stirred for 3 hours. Then it was cooled to room temperature and quenched with cold water and extracted with dichloromethane. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified over a C18 column (acetonitrile/water, containing 0.1% formic acid) to afford 4-(4-fluorophenyl)oxazole. LC/MS (method A) retention time = 1.18 min; [M+H]+ = 164.2 Step 2: Preparation of 5-bromo-4-(4-fluorophenyl)oxazole
Figure imgf000180_0002
To a stirred mixture of 4-(4-fluorophenyl)oxazole (1.00 g, 6.13 mmol) in acetonitrile (20.0 mL) at 0 °C was added, portionwise, 1-bromopyrrolidine-2,5-dione (1.36 g, 7.66 mmol, 1.25 eq.). The resulting mixture was stirred at room temperature for 12 hours, and then quenched with water. The mixture was concentrated under reduced pressure to remove the acetonitrile and the residue was extracted with dichloromethane. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/petroleum ether) to afford 5-bromo-4-(4- fluorophenyl)oxazole. LC/MS (method A) retention time = 1.39 min; [M+H]+ = 242.0 Step 3: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)oxazol-5-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 62) To a solution of 5-bromo-4-(4-fluorophenyl)oxazole (180 mg, 0.744 mmol) in dioxane/water (v/v= 5/1, 12.0 mL) was added [3-[6-(methoxycarbonylamino)-3-pyridyl]imidazo[1,2-a]pyridin-6-yl]boronic acid (232 mg, 0.744 mmol, 1.00 eq.), potassium carbonate (257 mg, 1.86 mmol, 2.50 eq.) and Pd(dppf)Cl 2 (54.5 mg, 0.0743 mmol, 0.100 eq.) and the reaction mixture was put under an atmosphere of nitrogen. The mixture was heated at 80 °C and then stirred for 2 hours. The resulting mixture was cooled to room temperature and then diluted with water, and extracted with dichloromethane/MeOH (v/v = 10:1). The combined organic layers were concentrated under reduced pressure and the crude residue was purified by flash chromatography over silica gel (dichloromethane/MeOH). After concentration the resulting material was further purified by trituration with acetonitrile to afford methyl N-[5-[6-[4-(4- fluorophenyl)oxazol-5-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white powder. LC/MS (method A) retention time = 1.05 min; [M+H]+ = 430.2 1 H NMR (400 MHz, DMSO-d6, ppm) δ = 10.56 (s, 1H), 8.78 (s, 1H), 8.66 (s, 1H), 8.53 (d, J = 1.8 Hz, 1H), 8.35 (s, 1H), 8.00 (m, 4H), 7.70 (dd, J = 8.7, 5.5 Hz, 2H), 7.28 (t, J = 8.8 Hz, 2H), 3.73 (s, 3H). Example 14: preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 31)
Figure imgf000181_0001
(Compound 31) Step 1: Preparation of 3-chloro-6-(1-methylpyrazol-3-yl)imidazo[1,2-a]pyridine
Figure imgf000181_0002
To a stirred solution of 6-bromo-3-chloro-imidazo[1,2-a]pyridine (5.00 g, 21.6 mmol) in dioxane/water (v/v = 5/1, 60.0 mL) was added 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (4.72 g, 22.7 mmol), potassium carbonate (7.46 g, 54.0 mmol) and Pd(dppf)Cl2 (1.58 g, 2.16 mmol) under an atmosphere of nitrogen. The reaction mixture was heated at 65 °C and stirred for 4 hours. The resulting mixture was then cooled to room temperature, diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduce pressure, and the crude residue was purified by flash chromatography over silica gel (eluting with MeOH/dichloromethane, 0% to 3%) to afford 3-chloro-6-(1-methylpyrazol-3- yl)imidazo[1,2-a]pyridine as a yellow oil. LCMS (method A) retention time = 0.86; [M+H]+ = 233.2. Step 2: Preparation of 6-(4-bromo-1-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine To a solution of 3-chloro-6-(1-methylpyrazol-3-yl)imidazo[1,2-a]pyridine (5.90 g, 25.4 mmol) in acetonitrile at 0 °C (140.0 mL) was added 1-bromopyrrolidine-2,5-dione (4.51 g, 25.4 mmol) by portions. The resulting solution was warmed to room temperature and stirred for an addition 16 hours. The resulting mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure, and the crude residue was purified by flash chromatography over silica gel (eluting with EtOAc/petroleum ether) to afford 6-(4-bromo-1-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine as an off-white solid. LCMS (method A) retention time = 1.07 min; [M+H]+ = 313.1. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.71 (d, J = 1.1 Hz, 1H), 8.15 (s, 1H), 7.80 - 7.75 (m, 3H), 3.93 (s, 3H). Step 3: Preparation of 3-chloro-6-[4-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-3-yl]imidazo[1,2- a]pyridine
Figure imgf000182_0001
To a stirred solution of 6-(4-bromo-1-methyl-pyrazol-3-yl)-3-chloro-imidazo[1,2-a]pyridine (800 mg, 2.57 mmol) in dioxane/water (9.60 mL, v/v = 5/1) was added (4-fluoro-3-methoxy-phenyl)boronic acid (436 mg, 2.57 mmol, 1.00 eq.), potassium carbonate (887 mg, 6.42 mmol, 2.50 eq.) and Pd(dppf)Cl2 (188 mg, 0.257 mmol, 0.100 eq.) under the mixture put under an atmosphere of nitrogen. The mixture was heated at 65 °C and stirred for 6 hours. The reaction mixture was then cooled, the resulting mixture was diluted with water, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure, and the crude residue was purified by flash chromatography over silica gel (dichloromethane/methanol) to afford 3- chloro-6-[4-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-3-yl]imidazo[1,2-a]pyridine as an off-white solid. LC/MS (method A) retention time = 1.18 min; [M+H]+ = 357.2 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.24 (s, 1H), 8.04 (s, 1H), 7.72 (s, 1H), 7.64 (d, J = 9.4 Hz, 1H), 7.34 (dd, J = 9.4, 1.4 Hz, 1H), 7.22 - 7.17 (m, 1H), 7.12 (dd, J = 8.4, 2.0 Hz, 1H), 6.84 (dd, J = 8.2, 4.2, 2.0 Hz, 1H), 3.95 (s, 3H), 3.74 (s, 3H). Step 4: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 31) To a stirred solution of 3-chloro-6-[4-(4-fluoro-3-methoxy-phenyl)-1-methyl-pyrazol-3-yl]imidazo[1,2- a]pyridine (200 mg, 0.561 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2- pyridyl]carbamate (234 mg, 0.841 mmol, 1.50 eq.) in dioxane/water (5.00 mL, v/v = 4/1) was added potassium carbonate (194 mg, 1.40 mmol, 2.50 mmol) and Bretthpos Pd G3 (CAS 1470372-59-8, 51 mg, 0.056 mmol, 0.10 eq.) and the reaction mixture was put under a nitrogen atmosphere. The mixture was then heated at 100 °C and stirred for 3 hours. The reaction mixture was then cooled, diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure, and the crude residue was purified by flash chromatography over silica gel (dichloromethane/methanol) to give a solid sample, which was triturated with acetonitrile to afford methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-1-methyl- pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid. LC/MS (method A) retention time = 1.00 min; [M+H]+ = 473.3 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.40 (s, 1H), 8.42 (d, J = 1.8 Hz, 1H), 8.27 (s, 1H), 7.97 (s, 1H), 7.91 (d, J = 8.6 Hz, 1H), 7.78 (s, 1H), 7.78 - 7.74 (m, 1H), 7.66 (d, J = 9.4 Hz, 1H), 7.41 (d, J = 10.8 Hz, 1H), 7.17 (dd, J = 11.4, 8.2 Hz, 1H), 7.07 (dd, J = 8.2, 2.0 Hz, 1H), 6.86 - 6.81 (m, 1H), 3.92 (s, 3H), 3.73 (s, 3H), 3.72 (s, 3H). Example 15: preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 25)
Figure imgf000183_0001
(Compound 25) Step 1: Preparation of methyl 8-methylimidazo[1,2-a]pyridine-6-carboxylate
Figure imgf000183_0002
To a stirred solution of methyl 8-bromoimidazo[1,2-a]pyridine-6-carboxylate (500 mg, 1.76 mmol) and methylboronic acid (216 mg, 3.53 mmol) in THF was added potassium carbonate (488 mg, 3.53 mmol) and Pd(dppf)Cl2 (129 mg, 0.176 mmol), and the reaction mixture was degassed with argon for 2 min. The reaction mixture was heated at 80 °C and stirred for 16 hours. The reaction mixture was then cooled to room temperature, filtered through a pad of celite, and the filtrate was washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford methyl 8- methylimidazo[1,2-a]pyridine-6-carboxylate as an off white solid. 1H NMR (400 MHz, CDCl3, ppm) δ = 2.64 (s, 3H), 3.94 (s, 3H), 7.53 (s, 1H), 7.63 - 7.67 (m, 1H), 7.67 - 7.71 (m, 1H), 8.80 (s, 1H). Step 2: Preparation of methyl 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxylate
Figure imgf000184_0001
To a mixture methyl 8-methylimidazo[1,2-a]pyridine-6-carboxylate (0.50 g, 2.6 mmol) in acetonitrile (13 mL) under an atmosphere of argon at room temperature was added N-bromosuccinimide (0.53 g, 2.9 mmol, 1.1 eq.) The reaction mixture was stirred for 45 min and then quenched with 1M sodium sulfite aqueous solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 3-bromo-8- methyl-imidazo[1,2-a]pyridine-6-carboxylate as a pale beige solid. 1H NMR (400 MHz, CDCl3, ppm) δ = 8.78 (d, J = 0.7 Hz, 1H), 7.69 (s, 1H), 7.58 - 7.65 (m, 1H), 3.99 (s, 3H), 2.65 (s, 3H) Step 3: Preparation of 3-bromo-8-methyl-imidazo[1,2-a]-6-carboxylic acid
Figure imgf000184_0002
To a solution of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxylate (0.10 g, 0.37 mmol, 1.0 eq.) in THF (2.2 mL) / water (0.74 mL) was added lithium hydroxide monohydrate (0.018 g, 0.74 mmol, 2.0 eq.) and the reaction mixture was stirred for 18 hours at room temperature. The reaction mixture was then diluted with ethyl acetate, acidified with aqueous 2 M HCl solution, and the aqueous layer was extracted with ethyl acetate. The water layer was concentrated in vacuo and dried by several azeotropic evaporations using toluene which afforded 3-bromo-8-methyl-imidazo[1,2-a]-6-carboxylic acid as light beige solid which was used for the next step without further purification. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.66 - 8.70 (m, 1H), 8.03 (s, 1H), 7.73 (s, 1H), 2.58 (s, 3H). Step 4: Preparation of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxamide
Figure imgf000184_0003
To a stirred solution of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxylic acid ( 1.1 g, 4.1 mmol) in THF (14 mL) was added dimethylformamide (0.1 mL), follow by the slow addition of oxalyl chloride ( 584 mg, 4.51 mmol, 1.10 eq.), after which the reaction mixture heated to 50 °C and stirred for 1 hour. The reaction mixture was then cooled to room temperature, and an ammonium hydroxide solution (25% in water), (2.30 g, 16.4 mmol) was added dropwise. The reaction mixture was then again heated to 50 °C and stirred for 30 min. After cooling down to room temperature the reaction mixture was added to cold water. The precipitate was filtered and dried under reduced pressure to afford 3-bromo-8-methyl- imidazo[1,2-a]pyridine-6-carboxamide as an off-white solid which was used for the next step without further purification. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.72 (s, 1H), 8.24 (br s, 1H), 7.79 (s, 1H), 7.63 (s, 1H), 7.56 (br s, 1H), 2.50 (s, 3H). Step 5: Preparation of (N)-3-bromo-N-(dimethylaminomethylene)-8-methyl-imidazo[1,2-a]pyridine-6- carboxamide
Figure imgf000185_0001
To a stirred solution of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxamide (2.40 g, 8.97 mmol) in N.N-dimethylformamide dimethyl acetal (18.4 mL) was added acetic acid (1.13 g, 17.9 mmol, 2.00 eq.) and the reaction mixture was heated at 95 °C and stirred for 3 hours. The reaction mixture was cooled and slowly poured onto water, the precipitate that formed was filtered, and dried under reduced pressure to afford (N)-3-bromo-N-(dimethylaminomethylene)-8-methyl-imidazo[1,2-a]pyridine-6-carboxamide as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.91 (s, 1H), 8.69 (s, 1H), 7.79 (app s, 2H), 3.18 (s, 3H), 3.23 (s, 3H), 2.52 (s, 3H). Step 6: Preparation of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridine
Figure imgf000185_0002
To a stirred solution of (N)-3-bromo-N-(dimethylaminomethylene)-8-methyl-imidazo[1,2-a]pyridine-6- carboxamide (300 mg, 0.922 mmol) in dimethylformamide (3.00 mL) was added (4-fluoro-3-methoxy- phenyl)hydrazine hydrochloride (199 mg, 1.01 mmol, 1.10 eq.). The reaction mixture was heated at 95 °C and stirred for 3 hours before being slowly poured onto water. The water phase extracted with ethyl acetate, the combined organic layers were washed with water and brine (20.0 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 3-bromo-6-[2-(4-fluoro-3-methoxy- phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridine as a yellow solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.32 (s, 1H), 8.16 (dd, J = 1.6, 0.8 Hz, 1H), 7.76 (s, 1H), 7.48 (dd, J = 7.6, 2.4 Hz, 1H), 7.40 - 7.35 (m, 1H), 7.29 (t, J = 1.2 Hz, 1H), 7.09 - 7.06 (m, 1H), 3.81 (s, 3H), 2.47 (s, 3H). Step 7: Preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 25) To a stirred solution of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridine (400 mg, 0.975 mmol), methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 2-pyridyl]carbamate (332 mg, 1.17 mmol, 1.20 eq.) in 1,4-dioxane/water (v/v = 3:1, 6.00 mL) was added cesium carbonate (646 mg, 1.95 mmol, 2.00 eq.). The mixture was degassed with argon for 2 minutes, then added Cataxium-A-Pd-G3 (36.2 mg, 0.0487 mmol, 0.050 eq.) was added and the reaction mixture kept under inert atmosphere. The resulting reaction mixture was heated at 110 ºC and stirred for 1 hour under microwave condition. The reaction mixture was filtered through a pad of celite, and the celite was further washed with ethyl acetate. The filtrate was washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (dichloromethane/MeOH) to afford a solid that was further washed with pentane and dried under reduced pressure to afford the desired pure product methyl N-[5-[6-[2-(4-fluoro- 3-methoxy-phenyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid. LC/MS (Method F) retention time = 1.59 min; [M+H]+ = 474 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 8.37 (d, J = 2.0 Hz, 1H), 8.28 (s, 1H), 8.13 (s, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.62 (dd, J = 11.2, 2.4 Hz, 1H), 7.40 (dd, J = 10.0, 2.4 Hz, 1H), 7.37 (s, 1H), 7.33-7.28 (m, 1H), 7.04-7.00 (m, 1H), 3.77 (s, 3H), 3.74 (s, 3H), 2.52 (s, 3H). Example 16: preparation of ethyl 3-(4-fluorophenyl)-2-[3-[6-(methoxycarbonylamino)-3- pyridyl]imidazo[1,2-a]pyridin-6-yl]imidazole-4-carboxylate (compound 67)
Figure imgf000186_0001
(Compound 67) Step 1: Preparation of ethyl 3-(4-fluorophenyl)-2-iodo-imidazole-4-carboxylate To a stirred solution of ethyl 3-(4-fluorophenyl)imidazole-4-carboxylate (CAS 689250, commercially available and synthesis already described in ChemMedChem 2021, 16, 2195; 5.00 g, 21.3 mmol) in acetonitrile (80.0 mL) was added 1-iodopyrrolidine-2,5-dione (48.0 g, 213 mmol, 10.0 eq.) The reaction mixture was heated at 100 °C and stirred for 48 hours in a sealed tube. The reaction mixture then cooled, concentrated under reduced pressure, and the crude residue purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford ethyl 3-(4-fluorophenyl)-2-iodo-imidazole-4-carboxylate. 1H NMR (400 MHz, CDCl3, ppm) δ = 7.83 (s, 1H), 7.22 (s, 2H), 7.21 (d, J = 1.2 Hz, 2H), 4.17 (q, J = 7.0 Hz, 2H), 1.21 (t, J = 7.0 Hz, 3H). Step 2: Preparation of ethyl 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carboxylate
Figure imgf000187_0001
To a stirred solution of ethyl 3-(4-fluorophenyl)-2-iodo-imidazole-4-carboxylate (200 mg, 0.544 mmol) in dioxane/water (v/v = 4:1, 10.0 mL) was added imidazo[1,2-a]pyridin-6-ylboronic acid (176 mg, 1.09 mmol, 2.00 eq.) and cesium carbonate (531 mg, 1.63 mmol, 3.00 eq.). The reaction mixture was purged with argon for 10 minutes, then PdCl2(PPh3)2 (191 mg, 0.272 mmol, 0.500 eq.) was added and the resulting mixture heated at 100 °C and stirred for 2 hours under microwave irradiation microwave. The reaction mixture was cooled, filtered through a pad of celite, the filtrate was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the crude product ethyl 3-(4- fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carboxylate which was used in the following step without further purification. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.67 (s, 1H), 7.97 (s, 1H), 7.93 (s, 1H), 7.59 (d, J = 1.2 Hz, 1H), 7.52-7.49 (m, 2H), 7.45 (d, J = 9.2 Hz, 1H), 7.31 (t, J = 8.8 Hz, 2H), 6.95 (dd, J = 8.6, 2.0 Hz, 1H), 4.12 (q, J = 7.2 Hz, 2H), 1.13 (t, J = 7.2 Hz, 3H). Step 3: Preparation of ethyl 3-(4-fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4- carboxylate To ethyl 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carboxylate (430 mg, 1.17 mmol) in dimethylformamide (30.0 mL) was added 1-iodopyrrolidine-2,5-dione (289 mg, 1.28 mmol, 1.10 eq.) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture then was diluted with ice cold water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford ethyl 3-(4- fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4-carboxylate. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.00 (s, 1H), 7.97 (s, 1H), 7.72 (s, 1H), 7.62-7.57 (m, 3H), 7.42 - 7.32 (m, 3H), 4.13 (q, J = 7.2 Hz, 2H), 1.14 (t, J = 7.20 Hz, 3H). Step 4: Preparation of ethyl 3-(4-fluorophenyl)-2-[3-[6-(methoxycarbonylamino)-3-pyridyl]imidazo[1,2- a]pyridin-6-yl]imidazole-4-carboxylate (Compound 67) To a stirred solution of ethyl 3-(4-fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4- carboxylate (200 mg, 0.395 mmol) in 1,4-dioxane/water (v/v = 5:1, 20.0 mL) was added methyl N-[5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (132 mg, 0.474 mmol, 1.20 eq.) and cesium carbonate (257 mg, 0.790 mmol, 2.00 eq.). The reaction mixture was purged with argon for 10 minutes, then cataCXium® A (7 mg, 0.02 mmol, 0.05 eq.) was added and the resulting reaction mixture was heated at 100 °C and stirred for 1 hour under microwave irradiation. The rection mixture was cooled, filtered through a pad of celite, the filtrate was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash column chromatography over silica gel (ethyl acetate/hexane) to afford ethyl 3-(4-fluorophenyl)-2-[3-[6-(methoxycarbonylamino)-3- pyridyl]imidazo[1,2-a]pyridin-6-yl]imidazole-4-carboxylate. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.47 (s, 1H), 8.33 (d, J = 2.4 Hz, 1H), 8.02 - 7.94 (m, 3H), 7.78 (s, 1H), 7.68 - 7.67 (m, 2H), 7.53 - 7.52 (m, 3H), 7.24 (t, J = 8.8 Hz, 2H), 4.10 (q, J = 7.2 Hz, 2H), 3.75 (s, 3H), 1.12 (t, J = 7.2 Hz, 3H). Example 17: preparation of methyl N-[5-[6-[5-cyano-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 71) (Compound 71) Step 1: Preparation of 3-(4-fluorophenyl)imidazole-4-carboxamide
Figure imgf000189_0001
A solution of ethyl 3-(4-fluorophenyl)imidazole-4-carboxylate (90.0 % purity, 100 mg, 0.384 mmol) in aqueous ammonia (67.3 mg, 1.92 mmol) in seal tube was heated at 120 °C and stirred for 24 hours. The reaction mixture was then cooled, diluted with water, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-(4-fluorophenyl)imidazole-4-carboxamide which was used without further purification. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 7.92 (s, 1H), 7.81 (br s, 1H), 7.67 (s, 1H), 7.36 - 7.44 (m, 2H), 7.34 - 7.26 (m, 2H), 7.23 (br s, 1H). Step 2: Preparation of 3-(4-fluorophenyl)imidazole-4-carbonitrile
Figure imgf000189_0002
To a solution of 3-(4-fluorophenyl)imidazole-4-carboxamide (70.0 % purity, 1.50 g, 5.12 mmol) in THF (5.00 mL) and pyridine (1.21 g, 15.4 mmo, 3.00 eq.) at 0 °C, was added trifluoro acetic anhydride (1.61 g, 7.68 mmol, 1.50 eq.). The resulting reaction mixture was warmed to room temperature and stirred for an additional 4 hours. The reaction mixture was concentrated under reduced pressure and the crude residue diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 3-(4- fluorophenyl)imidazole-4-carbonitrile. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.39 (d, J = 0.8 Hz, 1H), 8.08 (d, J = 0.8 Hz, 1H), 7.73-7.68 (m, 2H), 7.49 (t, J = 8.8 Hz, 2H). Step 3: Preparation of 2-bromo-3-(4-fluorophenyl)imidazole-4-carbonitrile To a stirred solution of 3-(4-fluorophenyl)imidazole-4-carbonitrile (310 mg, 1.62 mmol) in chloroform (10.0 mL) was added 1-bromopyrrolidine-2,5-dione (1333 mg, 8.12 mmol). The resulting reaction mixture was heated at 120 °C and stirred for 6 hours in a seal tube. The reaction mixture was then cooled and concentrated under reduced pressure, the crude residue was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 2-bromo-3-(4-fluorophenyl)imidazole-4- carbonitrile. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 7.74 (s, 1H), 7.42-7.41 (m, 2H), 7.32-7.30 (m, 2H). Step 4: Preparation of 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carbonitrile
Figure imgf000190_0001
To a stirred solution of 2-bromo-3-(4-fluorophenyl)imidazole-4-carbonitrile (60.0 mg, 0.223 mmol) in dioxane/water (v/v = 4:1, 5.00 mL) was added imidazo[1,2-a]pyridin-6-ylboronic acid (54 mg, 0.34 mmol, 1.5 eq.) and cesium carbonate (145 mg, 0.447 mmol, 2.00 eq.). The reaction mixture was purged with argon for 10 minutes, and then [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (18 mg, 0.23 mmol, 0.10 eq.) was added and the reaction was heated at 100 °C and stirred for 2 hours under microwave irradiation. The reaction mixture was then cooled, filtered through at pad of celite, the filtrate was diluted with water and the aqueous layer extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4- carbonitrile. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.78 (s, 1H), 8.20 (s, 1H), 8.03 (s, 1H), 7.67 (m, 2H), 7.61 (d, J = 1.2 Hz, 1H), 7.51-7.48 (m, 3H), 6.95 (dd, J = 9.4, 1.6 Hz, 1H). Step 5: Preparation of 3-(4-fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4-carbonitrile To a solution of 3-(4-fluorophenyl)-2-imidazo[1,2-a]pyridin-6-yl-imidazole-4-carbonitrile (180 mg, 0.588 mmol) in dimethylformamide (10.0 mL) was added 1-iodopyrrolidine-2,5-dione (145 mg, 0.646 mmol, 1.10 eq.) and the resulting reaction mixture was stirred at room temperature for 12 hours. After completion it was diluted with ice water and extracted with ethyl acetate . The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 3-(4-fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4-carbonitrile. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.23 (s, 1H), 8.11 (q, J = 0.80 Hz, 1H), 7.76-7.72 (m, 3H), 7.62 (dd, J = 9.6, 0.8 Hz, 1H), 7.49 (t, J = 6.8 Hz, 2H), 7.37 (dd, J = 9.6, 1.6 Hz, 1H). Step 6: Preparation of methyl N-[5-[6-[5-cyano-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 71) To a stirred solution of 3-(4-fluorophenyl)-2-(3-iodoimidazo[1,2-a]pyridin-6-yl)imidazole-4-carbonitrile (150 mg, 0.343 mmol) in dioxane/water(v/v = 5:1, 10.0 mL) was added methyl N-[5-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (114 mg, 0.411 mmol, 1.20 eq.) and cesium carbonate (223 mg, 0.685 mmol, 2.00 eq.). The reaction mixture was purged with argon for 10 minutes and then cataCXium® A (6 mg, 0.017mmol, 0.050 eq.) was added and the resulting reaction mixture heated at 100 °C and stirred for 1 hour under microwave irradiation. The reaction mixture was cooled to room temperature, filtered through a pad of celite, the filtrate was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford methyl N-[5-[6-[5-cyano-1-(4-fluorophenyl)imidazol-2- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.44 (s, 1H), 8.34 (dd, J = 0.4 Hz, 1H), 8.20 (s, 1H), 8.14 (m, 1H), 7.96 (dd, J = 8.8, 0.4 Hz, 1H), 7.81 (s, 1H), 7.71-7.62 (m, 4H), 7.48-7.38 (m, 3H), 3.74 (s, 3H). Example 18: preparation of methyl N-[5-[6-[3-(4-fluorophenyl)-5-methyl-imidazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 41) (Compound 41) Step 1: Preparation of 1-(4-fluorophenyl)-5-iodo-4-methyl-imidazole
Figure imgf000192_0001
A solution of 1-(4-fluorophenyl)-4-methyl-imidazole (CAS 924709-34-2; synthesized as described in J. Org. Chem.2007, 72, 6219; 50.0 mg, 0.270 mmol) in dimethylformamide (2.00 mL) was charged with 1-iodopyrrolidine-2,5-dione (152 mg, 0.674 mmol, 2.50 eq.) and stirred at room temperature for 16 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude to afford 1-(4-fluorophenyl)-5-iodo-4-methyl-imidazole. 1H NMR (400 MHz, CDCl3, ppm) δ = 7.73 (s, 1H), 7.31 - 7.28 (m, 2H), 7.21 - 7.17 (m, 2H), 2.31 (s, 3H). Step 2: Preparation of 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]imidazo[1,2-a]pyridine
Figure imgf000192_0002
To a solution of 1-(4-fluorophenyl)-5-iodo-4-methyl-imidazole (250 mg, 0.786 mmol) and imidazo[1,2- a]pyridin-6-ylboronic acid (153 mg, 0.943 mmol, 1.20 eq.) in dioxane/water (v/v = 3:1, 10.0 mL) was added cesium carbonate (512 mg, 1.57 mmol, 2.00 eq.) and the reaction mixture was degassed with argon for 10 minutes. To this mixture Pd(PPh3)4 (91 mg, 0.079 mmol, 0.10 eq.) was added and it was heated at 100 °C under microwave irradiation for 1 hour. The reaction mixture was cooled to room temperature, concentrated under reduced pressure and purified by flash chromatography over silica gel (dichloromethane/MeOH) to afford 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]imidazo[1,2-a]pyridine as an off-white solid. 1H NMR (400 MHz, CDCl3, ppm) δ = 8.00 (s, 1H), 7.66-7.65 (m, 2H), 7.57 (s, 1H), 7.50-7.48 (d, J = 9.2 Hz, 1H), 7.15-7.11 (m, 2H), 7.08-7.03 (t, J = 7.6 Hz, 2H), 6.76-6.73 (dd, J = 9.2, 1.6 Hz, 1H), 2.34 (s, 3H). Step 3: Preparation of 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]-3-iodo-imidazo[1,2-a]pyridine
Figure imgf000193_0001
A solution of 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]imidazo[1,2-a]pyridine (100 mg, 0.325 mmol) in dimethylformamide (5.00 mL) was charged with N-iodosuccinimide (80.4 mg, 0.357 mmol, 1.10 eq.) and the reaction mixture was stirred at room temperature for 16 hours. Afterwards it was diluted with water (20.0 mL) and extracted with ethyl acetate. The combined organic layers were washed with water (20.0 mL) and brine (20.0 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel cartridge (ethyl acetate/hexane) to afford 6-[3-(4- fluorophenyl)-5-methyl-imidazol-4-yl]-3-iodo-imidazo[1,2-a]pyridine. 1H NMR (400 MHz, CDCl3, ppm) δ = 7.96 - 7.94 (dd, J = 1.5 Hz, J = 0.88 Hz, 1H), 7.71 (s, 2H), 7.50 - 7.48 (d, J = 9.2 Hz, 1H), 7.17 - 7.14 (m, 2H), 7.10 - 7.06 (m, 2H), 6.85 - 6.82 (dd, J = 9.3 Hz, J = 1.6 Hz, 1H), 2.39 (s, 3H). Step 4: Preparation of methyl N-[5-[6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 41) To a solution of 6-[3-(4-fluorophenyl)-5-methyl-imidazol-4-yl]-3-iodo-imidazo[1,2-a]pyridine (80.0 mg, 0.182 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (64.5 mg, 0.227 mmol, 1.25 eq.) in 1,4-dioxane/water (v/v = 3:1, 10.0 mL) was added cesium carbonate (118 mg, 0.363 mmol, 2.00 eq.). It was degassed with argon for 10 minutes, then [2-(2-aminophenyl)phenyl]- chloro-palladium;dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane (7.15 mg, 0.009 mmol, 0.05 eq.) was added and it was irradiated under microwave conditions at 100 °C for 1 hour. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (ethyl acetate/hexane) to afford the title compound, which was further purified by C-18 column chromatography (water/acetonitrile) to afford methyl N-[5-[6-[3-(4-fluorophenyl)-5-methyl-imidazol-4- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 8.47 - 8.46 (dd, J = 2.4 Hz, J = 0.6 Hz, 1H), 8.24 (s, 1H), 7.97 - 7.95 (d, J = 8.8 Hz, 1H), 7.90 (s, 1H), 7.87 - 7.84 (dd, J = 11.2 Hz, J = 2.4 Hz, 1H), 7.80 (s, 1H), 7.59 - 7.56 (dd, J = 10 Hz, J = 0.8 Hz, 1H), 7.38 - 7.35 (m, 2H), 7.29 - 7.24 (m, 2H), 6.93 - 6.90 (dd, J = 11.2 Hz, J = 1.6 Hz, 1H), 3.72 (s, 3H), 2.22 (s, 3H). Example 19: preparation of methyl N-[5-[6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 72) (Compound 72) Step 1: Preparation of 2-bromo-5-chloro-1-(4-fluorophenyl)imidazole
Figure imgf000194_0001
To a solution of 5-chloro-1-(4-fluorophenyl)imidazole (synthesized as described in Science of Synthesis 2002, 12, 325-528; 250 mg, 1.08 mmol) in chloroform (5.00 mL) was added N-bromosuccinimide (226 mg, 1.24 mmol, 1.15 eq.), followed by 2-[(E)-(1-cyano-1-methyl-ethyl)azo]-2-methyl-propanenitrile (17.7 mg, 0.108 mmol, 0.100 eq.) at room temperature. The reaction mixture was heated at 50 °C and stirred for 5 hours. The mixture was then cooled to room temperature, concentrated under reduced pressure crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 2- bromo-5-chloro-1-(4-fluorophenyl)imidazole as a brown solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 7.34 (m, 2 H), 7.21 (m, 2 H), 5.70 (s, 1 H). Step 2: Preparation of 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridine
Figure imgf000194_0002
To a stirred solution of 2-bromo-5-chloro-1-(4-fluorophenyl)imidazole (50.0 mg, 0.163 mmol) and imidazo[1,2-a]pyridin-6-ylboronic acid (30 mg, 0.19 mmol, 1.15 eq.) in dioxane/water (v/v = 3:1, 5.00 mL) was added potassium carbonate (45.1 mg, 0.327 mmol, 2.00 eq.). The reaction mixture was degassed with argon for 2 minutes, then Pd(dppf)Cl2 (12 mg, 0.016 mmol, 0.10 eq.) was added. The mixture was then heated to 100 °C under microwave irradiation for 45 min. After cooling to room temperature, the reaction mixture was filtered and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2- a]pyridine as a brown solid. 1H NMR (400 MHz, CDCl3, ppm) δ = 8.80 (dd, J = 1.6, 0.8 Hz, 1H), 7.88 (dd, J = 9.6, 2.0 Hz, 1H), 7.71 - 7.64 (m, 4H), 7.42 - 7.39 (m, 2H), 7.28 - 7.23 (m, 2H). Step 3: Preparation of 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]-3-iodo-imidazo[1,2-a]pyridine
Figure imgf000195_0001
To a solution of 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridine (160 mg, 0.435 mmol) in dimethylformamide (5.00 mL) was added N-iodosuccinimide (108 mg, 0.478 mmol, 1.10 eq.) and the resulting reaction mixture was stirred at room temperature for 16 hours. Afterwards, it was poured into water and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure, and crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[5-chloro-1-(4-fluorophenyl)imidazol- 2-yl]-3-iodo-imidazo[1,2-a]pyridine as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.77 (dd, J = 1.6, 1.2 Hz, 1H), 8.21 (s, 1H), 7.93 - 7.90 (dd, J = 9.2, 1.6 Hz, 1H), 7.78 (s, 1H), 7.75 - 7.73 (dd, J = 9.6, 0.8 Hz, 1H), 7.70 - 7.66 (dd, J = 8.8, 4.8 Hz, 2H), 7.50 - 7.46 (t, J = 8.8 Hz, 2H). Step 4: Preparation of methyl N-[5-[6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 72) To a solution of 6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]-3-iodo-imidazo[1,2-a]pyridine (100 mg, 0.205 mmol), methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (65.6 mg, 0.236 mmol, 1.15 eq.) in 1,4-dioxane/water (v/v = 3:1, 5.00 mL) was added potassium carbonate (57 mg, 0.41 mmol, 2.0 eq.) and the reaction mixture was degassed with argon for 2 minutes. [1,1'-Bis (diphenylphosphino)ferrocene]dichloropalladium(II) (150 mg, 0.205 mmol, 1.00 eq.) was added to the and the resulting reaction mixture was heated at 100 ºC under microwave irradiation for 1 hour. The reaction mixture wat then cooled to room temperature, filtered, and washed with ethyl acetate. The filtrate was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude mixture was purified by silica gel column chromatography (ethyl acetate/n-hexane) to afford methyl N- [5-[6-[5-chloro-1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off- white solid. 1H NMR (400 MHz, DMSO-d6, ,ppm) δ = 10.43 (s, 1H), 8.87 (s, 1H), 8.59 (s, 1H), 8.17 (s, 1H), 8.14 (d, J = 8.8 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.90 -7.78 (m, 3H), 7.64 (s, 2H), 7.46 (t, J = 8.4 Hz, 2H), 3.71 (s, 3H). Example 20: preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol- 3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 26) (Compound 26) Step 1: Preparation of 3-bromoimidazo[1,2-a]pyridine-6-carbohydrazide
Figure imgf000196_0001
To a solution of methyl 3-bromoimidazo[1,2-a]pyridine-6-carboxylate (1.00 g, 3.80 mmol) in methanol (5.43 mL) was added hydrazine hydrate (0.226 mL, 4.56 mmol, 1.20 eq.). The reaction mixture was stirred overnight at 70 °C, then it was cooled down to room temperature, water was added and the precipitate was filtered and washed with water to afford 3-bromoimidazo[1,2-a]pyridine-6- carbohydrazide as a white solid. LC/MS (method A) retention time = 0.19 min; [M+H]+ = 255 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.07 (br s, 1H), 8.79 (s, 1H), 7.82 (s, 1H), 7.72 - 7.77 (m, 1H), 7.67 - 7.72 (m, 1H), 4.58 (br s, 2H). Step 2: Preparation of 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole
Figure imgf000196_0002
To 3-bromoimidazo[1,2-a]pyridine-6-carbohydrazide (500 mg, 1.96 mmol) was added triethyl orthoacetate (3.67 mL, 19.6 mmol, 10.0 eq.) and the reaction mixture was heated at 130 °C and stirred for 90 min. The reaction mixture was cooled and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.359 mL, 2.35 mmol, 1.20 eq.) was added. The reaction mixture was heated again at 130 °C and stirred for an additional 20 min. After completion the mixture was cooled down to room temperature, water was added, and the precipitate that formed was filtered and washed with water to afford 2-(3-bromoimidazo[1,2- a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole as a beige solid. LC/MS (method A) retention time = 0.63 min; [M+H]+ = 279 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.71 - 8.81 (m, 1H), 7.88 - 7.92 (m, 1H), 7.84 - 7.87 (m, 2H), 2.60 - 2.66 (s, 3H). Step 3: Preparation of 3-bromo-6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine To a solution of 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole (200 mg, 0.717 mmol) in acetic acid (2.39 mL) was added 4-fluoro-3-methoxyaniline (532 mg, 3.58 mmol, 5.00 eq.). The reaction mixture was heated at 130 °C and stirred for 45 minutes. The reaction mixture was then cooled down to room temperature and slowly quenched with a saturated NaHCO3 solution. The aqueous phase was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethylacetate/EtOH/cyclohexane) to afford 3-bromo-6-[4-(4-fluoro- 3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine as a beige solid. LC/MS (method A) retention time = 0.76 min; [M+H]+ = 402 1H NMR (400 MHz, CDCl3, ppm) δ = 8.24 (dd, J = 1.6, 0.9 Hz, 1H), 7.63 (s, 1H), 7.54 (dd, J = 9.4, 1.1 Hz, 1H), 7.36 (dd, J = 9.4, 1.8 Hz, 1H), 7.30 (d, J = 9.1 Hz, 1H), 6.81 - 6.92 (m, 2H), 3.89 (s, 3H), 2.41 (s, 3H). Step 4: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 26) In a microwave test tube was added 3-bromo-6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine (260 mg, 0.646 mmol), 2-methoxycarbonylaminopyridine-5-boronic acid pinacol ester (265 mg, 0.905 mmol, 1.40 eq.), cesium carbonate (319 mg, 0.970 mmol, 1.50 eq.), 2- methyltetrahydrofuran (8.40 mL), water (2.80 mL) and tetrakis(triphenylphosphine)palladium(0) (7.70 mg, 0.0323 mmol, 0.05 eq.). The reaction mixture was purged with argon and heated at 100 °C for 30 min under microwave irradiation. The suspension was cooled to room temperature, petroleum ether was added, the suspension was filtered and successively washed with water and petroleum ether. The precipitate was dissolved in chloroform at 50 °C and filtered. The filtrate was concentrated to give methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate as a white solid. LC/MS (method A) retention time = 0.65 min; [M+H]+ = 474 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.39 (s, 1H), 8.33 - 8.40 (m, 1H), 8.10 (dd, J = 1.6, 0.9 Hz, 1H), 7.96 (dd, J = 8.7, 0.7 Hz, 1H), 7.79 (s, 1H), 7.70 (dd, J = 9.4, 0.7 Hz, 1H), 7.66 (dd, J = 8.5, 2.4 Hz, 1H), 7.53 (dd, J = 9.4, 1.8 Hz, 1H), 7.44 (dd, J = 7.6, 2.5 Hz, 1H), 7.30 (dd, J = 11.1, 8.5 Hz, 1H), 6.99 - 7.06 (m, 1H), 3.77 (s, 3H), 3.74 (s, 3H), 2.25 (s, 3H). Example 21: Preparation of methyl N-[5-[6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 69) (Compound 69) Step 1: Preparation of 5-(4-fluorophenyl)pyrimidin-4-ol
Figure imgf000198_0001
To a stirred solution of 5-bromopyrimidin-4-ol (500 mg, 2.86 mmol) and (4-fluorophenyl)boronic acid (460 mg, 3.29 mmol, 1.15 eq.) in dioxane/water (v/v = 5:1, 10.0 mL) was added sodium carbonate (909 mg, 8.57 mmol, 3.00 eq.). The reaction mixture was degassed with argon for 5 minutes, then Pd(PPh3)4 (330 mg, 0.286 mmol, 0.100 eq.) was added and it was stirred under nitrogen at 100 °C for 16 hours. The reaction mixture was then cooled down to room temperature, NaOH (2N, 5.00 mL) was added and stirring continued for 10 minutes. The reaction mixture was extracted with ethyl acetate, the aqueous layer was acidified with aqueous HCl 1N and extracted again with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 5-(4-fluorophenyl)pyrimidin-4-ol as a yellow solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.10 - 8.22 (m, 1 H), 7.88 - 7.92 (m, 1 H), 7.80 - 7.85 (m, 1 H), 7.75 - 7.80 (m, 1 H), 7.20 - 7.26 (m, 1 H), 7.10 - 7.20 (m, 2 H). Step 2: Preparation of 4-chloro-5-(4-fluorophenyl)pyrimidine
Figure imgf000198_0002
A mixture of 5-(4-fluorophenyl)pyrimidin-4-ol (500 mg, 2.23 mmol) and phosphoryl trichloride (2.05 mL, 22.3 mmol, 10.0 eq.) was heated at 110 °C and stirred for 3 hours. The mixture was then cooled and concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with saturated NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 4-chloro-5-(4-fluorophenyl)pyrimidine as an off-white solid. 1H NMR (400 MHz, CDCl3, ppm) δ = 8.98 (s, 1H), 8.64 (s, 1H), 7.48 - 7.43 (m, 2H), 7.23 - 7.19 (m, 2H). Step 3: Preparation of 6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridine
Figure imgf000199_0001
To a stirred solution of 4-chloro-5-(4-fluorophenyl)pyrimidine (350 mg, 1.51 mmol) and imidazo[1,2- a]pyridin-6-ylboronic acid (293 mg, 1.81 mmol, 1.20 eq.) in dioxane/water (v/v = 3:1, 10.0 mL) was added cesium carbonate (984 mg, 3.02 mmol, 2.00 eq.). The reaction mixture was degassed with argon for 2 minutes, then Pd(dppf)Cl2 (110 mg, 0.151 mmol, 0.100 eq.) was added and the reaction mixture was heated at 100 °C and stirred 1 hour under microwave irradiation. After cooling down to room temperature, the reaction mixture was filtered through a pad of celite which was further washed with ethyl acetate. The filtrate was washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridine as yellow solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 9.27 (s, 1H), 8.86 (s, 2H), 8.03 (s, 1H), 7.60 (d, J = 1.2 Hz, 1H), 7.45 - 7.41 (m, 3H), 7.29 - 7.24 (m, 2H), 6.94- 6.91 (dd, J = 9.6 Hz, J = 1.6 Hz, 1H). Step 4: Preparation of 6-[5-(4-fluorophenyl)pyrimidin-4-yl]-3-iodo-imidazo[1,2-a]pyridine
Figure imgf000199_0002
To a stirred solution of 6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridine (100 mg, 0.310 mmol) in dimethylformamide (2.00 mL) was added N-iodosuccinimide (76.7 mg, 0.341 mmol, 1.10 eq.) and the reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was then cooled to room temperature and poured into water and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 6-[5-(4- fluorophenyl)pyrimidin-4-yl]-3-iodo-imidazo[1,2-a]pyridine as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 9.32 (s, 1H), 8.88 (s, 1H), 8.33 - 8.32 (dd, J =1.6 Hz, J = 0.8 Hz, 1H), 7.74 (s, 1H), 7.56 - 7.54 (dd, J = 9.4 Hz, J = 0.8 Hz, 1H), 7.48 - 7.45 (m, 2H), 7.30 - 7.25 (m, 3H). Step 5: Preparation of methyl N-[5-[6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 69) To a solution of 6-[5-(4-fluorophenyl)pyrimidin-4-yl]-3-iodo-imidazo[1,2-a]pyridine (200 mg, 0.432 mmol), methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (153 mg, 0.541 mmol, 1.25 eq.) in 1,4-dioxane/water (v/v = 3:1, 5.00 mL) was added cesium carbonate (282 mg, 0.865 mmol, 2.00 eq.). The reaction mixture was degassed with argon for 2 minutes, then [2-(2- aminophenyl)phenyl]-chloro-palladium;dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane (XPhosPdG2; 17.0 mg, 0.0216 mmol, 0.05 eq.) was added and the resulting reaction mixture was heated at 100 ºC under microwave irradiation for 1 hour. The reaction mixture was then cooled to room temperature, filtered through a pad of celite which was further washed using ethyl acetate. The filtrate was extracted with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford N-[5-[6-[5-(4-fluorophenyl)pyrimidin-4-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 9.27 (s, 1H), 8.82 (s, 1H), 8.40 - 8.37 (m, 2H), 7.95 - 7.93 (d, J = 8.6 Hz, 1H), 7.81 (s, 1H), 7.65 - 7.62 (m, 2H), 7.47 - 7.43 (m, 2H), 7.37 - 7.34 (dd, J = 9.4 Hz, J= 1.6 Hz, 1H), 7.27 - 7.23 (m, 2H), 3.73 (s, 1H). Example 22: preparation of methyl N-[5-[6-[4-(4-fluorophenyl)pyridazin-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 70)
Figure imgf000200_0001
(Compound 70) Step 1: Preparation of 4-(4-fluorophenyl)pyridazin-3-ol
Figure imgf000200_0002
To a solution of 4-bromopyridazin-3-ol (200 mg, 1.14 mmol) and (4-fluorophenyl)boronic acid (184 mg, 1.31 mmol, 1.15 eq.) in dioxane/water (v/v = 3:1, 5.00 mL) was added sodium carbonate (363 mg, 3.43 mmol, 3.00 eq.). The reaction mixture was degassed with argon for 2 minutes, then Pd(PPh3)4 (132 mg, 0.114 mmol, 0.100 eq.) was added and it was heated at 100 °C and stirred for 16 hours. The reaction mixture was then cooled to room temperature, NaOH (2N, 2.00 mL) was added and stirring continued for 10 minutes. The reaction mixture was diluted with ethyl acetate, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The aqueous layer was acidified with 1N HCl and again extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 4-(4-fluorophenyl)pyridazin-3-ol as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 13.24 (br s, 1H), 7.98 - 7.95 (m, 3H), 7.60 (d, J = 4.0 Hz, 1H), 7.32 - 7.27 (m, 2H). Step 2: Preparation of 3-chloro-4-(4-fluorophenyl)pyridazine
Figure imgf000201_0001
A suspension of 4-(4-fluorophenyl)pyridazin-3-ol (230 mg, 1.09 mmol) in phosphoryl trichloride (0.996 mL, 10.9 mmol, 10.0 eq.) was heated at 110 °C for 6 hours. The reaction mixture was then cooled to room temperature, concentrated under reduced pressure and the residue obtained was diluted with ethyl acetate. The solution was washed with saturated aqueous NaHCO3 and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 3-chloro-4-(4-fluorophenyl)pyridazine as a fluffy off-white solid. 1H NMR (400 MHz, CDCl3, ppm) δ = 9.17 (d, J = 5.2 Hz, 1H), 7.53 - 7.49 (m, 2H), 7.47 (d, J = 5.2 Hz, 1H), 7.24 - 7.20 (m, 2H). Step 3: Preparation of 6-[4-(4-fluorophenyl)pyridazin-3-yl]imidazo[1,2-a]pyridine
Figure imgf000201_0002
To a solution of 3-chloro-4-(4-fluorophenyl)pyridazine (2.25 g, 9.71 mmol) and imidazo[1,2-a]pyridin-6- ylboronic acid (1.89 g, 11.6 mmol, 1.20 eq.) in dioxane/water (v/v = 3:1, 20.0 mL) was added cesium carbonate (6.33 g, 19.4 mmol, 2.00 eq.). The reaction mixture was degassed with argon for 5 minutes, then Pd(dppf)Cl2 (710 mg, 0.971 mmol, 0.100 eq.) was added and the mixture was heated at 100 °C and stirred for 1 hour under microwave irradiation. The reaction mixture was filtered through a pad of celite which was further washed with ethyl acetate. The filtrate was washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[4-(4-fluorophenyl)pyridazin-3- yl]imidazo[1,2-a]pyridine as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 9.34 - 9.32 (d, J = 5.2 Hz, 1H), 8.88 - 8.87 (dd, J = 1.7 Hz, J = 0.9 Hz, 1H), 8.03 (s, 1H), 7.82 - 7.81 (d, J = 5.2 Hz, 1H), 7.61 (d, J = 1.2 Hz, 1H), 7.45 - 7.40 (m, 3H), 7.27 - 7.23 (m, 2H), 6.91 - 6.88 (dd, J = 9.3 Hz, J = 0.9 Hz, 1H). Step 4: Preparation of 6-[4-(4-fluorophenyl)pyridazin-3-yl]-3-iodo-imidazo[1,2-a]pyridine To a solution of 6-[4-(4-fluorophenyl)pyridazin-3-yl]imidazo[1,2-a]pyridine (500 mg, 1.60 mmol) in dimethylformamide (5.00 mL) was added 1-iodopyrrolidine-2,5-dione (432 mg, 1.92 mmol, 1.20 eq.). The resulting mixture was stirred for 16 hours at room temperature and then poured into water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[4-(4- fluorophenyl)pyridazin-3-yl]-3-iodo-imidazo[1,2-a]pyridine as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 9.35 (d, J = 5.2 Hz, 1H), 8.38 (q, J = 0.8 Hz, 1H), 7.84 - 7.82 (d, J = 5.2 Hz, 1H), 7.75 (s, 1H), 7.54 (dd, 1H), 7.47 - 7.43 (m, 2H), 7.28 - 7.23 (m, 2H), 7.17 (dd, 1H). Step 5: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 70) To a solution of 6-[4-(4-fluorophenyl)pyridazin-3-yl]-3-iodo-imidazo[1,2-a]pyridine (150 mg, 0.324 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (115 mg, 0.405 mmol, 1.25 eq.) in 1,4-dioxane/water (v/v = 3:1, 5.00 mL) was added cesium carbonate (211 mg, 0.649 mmol, 2.00 eq.) and the reaction mixture was degassed with argon for 2 minutes. CataCXium® A Pd G3 (24 mg, 0.032 mmol, 0.10 eq.) was added to the reaction mixture and it was heated at 100 ºC and stirred for 1 hour under microwave irradiation. The reaction mixture was cooled and then filtered through a pad of celite which was further washed with ethyl acetate. The filtrate was extracted with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude was purified by silica gel column chromatography (ethyl acetate/n-hexane) to afford methyl N-[5-[6-[4-(4- fluorophenyl)pyridazin-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 9.32 - 9.30 (d, J = 5.2 Hz, 1H), 8.49- 8.48 (dd, J = 1.6 Hz, 0.9 Hz, 1H), 8.43 - 8.42 (dd, J = 2.4 Hz, 0.7 Hz, 1H), 7.95 (d, J = 8 Hz, 1H), 7.82 (s, 1H), 7.79 (d, J = 5.6 Hz, 1H), 7.75 (dd, J = 8.6 Hz, 0.7 Hz, 1H), 7.62 (dd, J = 9.3 Hz, 0.8 Hz, 1H), 7.48 - 7.45 (m, 2H), 7.28 - 7.23 (m, 3H), 3.73 (s, 3H). Example 23: preparation of methyl N-[5-[6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 28) A solution of 2,3-dibromopyrazine (5.00 g, 21.0 mmol) in dioxane/water (v/v = 4:1, 80.0 mL) was purged with argon for 5 minutes, then (4-fluorophenyl)boronic acid (3.24 g, 23.1 mmol, 1.10 eq.), sodium carbonate (6.68 g, 63.1 mmol, 3.00 eq.) and Pd(PPh3)4 (2.43 g, 2.10 mmol), 0.100 eq.) were added and the reaction mixture was heated at 100 °C and stirred for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 2-bromo-3-(4- fluorophenyl)pyrazine. 1H NMR (400 MHz, CDCl3, ppm) δ = 8.60 (d, J = 2.4 Hz, 1H), 8.33 (d, J = 2.4 Hz, 1H), 7.78 (m, 2H), 7.19 (m, 2H). Step 2: Preparation of 6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridine
Figure imgf000203_0001
A solution of 2-bromo-3-(4-fluorophenyl)pyrazine (1.00 g, 3.79 mmol) in dioxane/water (v/v = 4:1, 60.0 mL) was purged with argon for 5 minutes, then imidazo[1,2-a]pyridin-6-ylboronic acid (737 mg, 4.55 mmol, 1.20 eq.), cesium carbonate (2.47 g, 7.59 mmol, 2.00 eq.) and Pd(PPh3)4 (438 mg, 0.379 mmol, 0.100 eq.) were added and the mixture was heated at 100 °C and stirred for 1 hour under microwave irradiation. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridine. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.83 (s, 1H), 8.75 (q, J = 2.0 Hz, 2H), 8.02 (s, 1H), 7.60-7.55 (m, 3H), 7.46 (d, J = 9.6 Hz, 1H), 7.23 (t, J = 8.8 Hz, 2H), 6.99 (d, J = 1.6 Hz, 1H). Step 3: Preparation of 6-[3-(4-fluorophenyl)pyrazin-2-yl]-3-iodo-imidazo[1,2-a]pyridine
Figure imgf000204_0001
To a solution of 6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridine (60.0 mg, 0.134 mmol) in dimethylformamide (5.00 mL) was added 1-iodopyrrolidine-2,5-dione (30 mg, 0.13 mmol, 1.0 eq.) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was then poured into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel to afford 6-[3-(4-fluorophenyl)pyrazin-2-yl]-3-iodo-imidazo[1,2- a]pyridine. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.78 (q, J = 2.8 Hz, 2H), 8.37 (t, J = 0.8 Hz, 1H), 7.75 (s, 1H), 7.59-7.53 (m, 3H), 7.26-7.18 (m, 3H). Step 4: Preparation of methyl N-[5-[6-[3-(4-fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 28) A solution of 6-[3-(4-fluorophenyl)pyrazin-2-yl]-3-iodo-imidazo[1,2-a]pyridine (200 mg, 0.471 mmol) in 1,4-dioxane/water (v/v = 5:1, 30.0 mL) was purge with argon for 5 minutes and then methyl N-[5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate (157 mg, 0.565 mmol, 1.20 eq.), cesium carbonate (307 mg, 0.942 mmol, 2.00 eq.) and cataCXium® A (8.44 mg, 0.0235 mmol, 0.05 eq.) were added. The reaction mixture was heated at 100 °C and stirred for 1 hour under microwave irradiation. The reaction mixture was then cooled to room temperature, diluted with water and extracted with ethyl acetate The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/n-hexane) to afford methyl N-[5-[6-[3-(4- fluorophenyl)pyrazin-2-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid. 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.45 (s, 1H), 8.73 (s, 2H), 8.48 (s, 1H), 8.42 (d, J = 2.40 Hz, 1H), 7.94 (d, J = 8.40 Hz, 1H), 7.82 (s, 1H), 7.71 (dd, J = 2.40, 8.80 Hz, 1H), 7.63-7.61 (m, 3H), 7.29- 7.26 (m, 3H), 3.73 (s, 3H). Example 24: preparation of methyl N-[5-[6-[2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 49) (Compound 49) Step 1: Preparation of 5-(4-fluorophenyl)-1-imidazo[1,2-a]pyridin-6-yl-pyrrolidin-2-one
Figure imgf000205_0001
To a stirred solution of 5-(4-fluorophenyl)pyrrolidin-2-one (commercially available CAS 90432-58-9; 259 mg, 1.44 mmol, 1.20 eq.) and 6-bromoimidazo[1,2-a]pyridine (237 mg, 1.20 mmol) in dioxane (4.00 mL) was added copper(I) iodide (23 mg, 0.12 mmol, 0.10 eq.), potassium carbonate (333 mg, 2.41 mmol, 2.00 eq.) and N,N’-dimethylethylenediamine (0.013 mL, 0.12 mmol, 0.10 eq.). The reaction mixture was stirred overnight at 100 °C, then it was cooled down to room temperature, diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water twice and once with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/hexane) to afford 5-(4-fluorophenyl)- 1-imidazo[1,2-a]pyridin-6-yl-pyrrolidin-2-one. LC/MS (method A) retention time = 0.60 min; [M+H]+ = 296 1H NMR (400 MHz, CDCl3, ppm) δ = 8.57 (d, J = 1.5 Hz, 1H), 7.54 (s, 1H), 7.49 (s, 1H), 7.42 (d, J = 9.8 Hz, 1H), 7.12 - 7.21 (m, 2H), 6.92 - 7.04 (m, 3H), 5.19 (t, J = 6.2 Hz, 1H), 2.55 - 2.83 (m, 3H), 1.93 - 2.08 (m, 1H). Step 2: Preparation of 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5-(4-fluorophenyl)pyrrolidin-2-one
Figure imgf000205_0002
To a suspension of 5-(4-fluorophenyl)-1-imidazo[1,2-a]pyridin-6-yl-pyrrolidin-2-one (210 mg, 0.711 mmol) in ethanol (10.0 mL) at 0 °C was added N-bromosuccinimide (153 mg, 0.853 mmol, 1.20 eq.) portion wise over 2 minutes. The resulting mixture was stirred at this temperature for 15 minutes, then it was concentrated under reduced pressure. The residue was portioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed three times with saturated aqueous NaHCO3 solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel to afford 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5-(4-fluorophenyl)pyrrolidin-2-one. LC/MS (method A) retention time = 0.80 min; [M+H]+ = 374 1H NMR (400 MHz, CDCl3, ppm) δ = 8.39 - 8.46 (m, 1H), 7.56 (s, 1H), 7.48 (dd, J = 9.8, 0.7 Hz, 1H), 7.19 - 7.25 (m, 2H), 7.17 (dd, J = 9.8, 2.2 Hz, 1H), 6.97 - 7.07 (m, 2H), 5.23 (dd, J = 7.1, 5.6 Hz, 1H), 2.61 - 2.90 (m, 3H), 2.03 - 2.12 (m, 1.H). Step 3: Preparation of methyl N-[5-[6-[2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate (Compound 49) To a 25 mL vial containing methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2- pyridyl]carbamate (162 mg, 0.582 mmol, 1.10 eq.), was added 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-5- (4-fluorophenyl)pyrrolidin-2-one (198 mg, 0.5291 mmol), potassium carbonate 1 M in water (2.00 mL, 2.00 mmol, 3.78 eq.), 2-methyltetrahydrofuran (4.00 mL), and tetrakis(triphenylphosphine)palladium(0) (31 mg, 0.027 mmol, 0.05 eq.). The reaction mixture was degassed with argon and left to stir in a sealed tube heated at 80 °C for 2 hours. The reaction mixture was then cooled and diethyl ether was added to the reaction mixture. The resulting solid that formed was filtered, and further washed with diethyl ether to afford methyl N-[5-[6-[2-(4-fluorophenyl)-5-oxo-pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate. LC/MS (method A) retention time = 0.68 min; [M+H]+ = 446 1H NMR (400 MHz, CDCl3, ppm) δ = 9.05 (br s, 1H), 8.40 (dt, J = 9.0, 1.1 Hz, 2H), 8.17 (d, J = 8.7 Hz, 1H), 7.70 (dd, J = 8.5, 2.4 Hz, 1H), 7.67 (s, 1H), 7.59 (d, J = 9.8 Hz, 1H), 7.25 (dd, J = 9.6, 2.0 Hz, 1H), 7.17 - 7.23 (m, 2H), 7.04 (t, J = 8.5 Hz, 2H), 5.17 (t, J = 6.2 Hz, 1H), 3.86 (s, 3H), 2.59 - 2.86 (m, 3H), 2.00 - 2.10 (m, 1H). Example 25: preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol- 3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 33)
Figure imgf000206_0001
(Compound 33) Step 1: Preparation of 3-bromoimidazo[1,2-a]pyridine-6-carboxamide
Figure imgf000206_0002
To a solution of 3-bromoimidazo[1,2-a]pyridine-6-carboxylic acid (430 mg, 1.69 mmol) in THF (5.65 mL) was added a drop of dimethylformamide followed by a slow addition of oxalyl chloride (0.159 mL, 1.78 mmol, 1.05 eq.). The reaction mixture was stirred for 40 minutes at 50 °C, and then ammonium hydroxide solution (28% in water, 0.848 mL, 6.78 mmol, 4.00 eq.) was added slowly and stirring continued for 30 minutes at 50 °C. The reaction mixture was cooled to room temperature, ice was added, the precipitate that formed was filtered, and washed with water to afford 3-bromoimidazo[1,2-a]pyridine-6-carboxamide as a white solid. LC/MS (method A) retention time = 0.24 min; [M+H]+ = 240 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.85 (s, 1H), 8.30 (br s, 1H), 7.82 (s, 1H), 7.78 (dd, J = 9.4, 1.8 Hz, 1H), 7.69 (dd, J = 9.4, 0.7 Hz, 1H), 7.61 (br s, 1H). Step 2: Preparation of (NE)-3-bromo-N-[1-(dimethylamino)ethylidene]imidazo[1,2-a]pyridine-6- carboxamide
Figure imgf000207_0001
To a suspension of 3-bromoimidazo[1,2-a]pyridine-6-carboxamide (300 mg, 1.25 mmol) in N,N- dimethylacetamide dimethyl acetal (0.280 mL, 1.87 mmol, 1.50 eq.) was added acetic acid (0.014 mL, 0.25 mmol, 0.20 eq.). The reaction mixture was heated at 95°C and stirred for 5 minutes. The reaction mixture was then cooled down to room temperature and water was added. The precipitate that thus formed was filtered to afford (NE)-3-bromo-N-[1-(dimethylamino)ethylidene]imidazo[1,2-a]pyridine-6- carboxamide as a white solid. LC/MS (method A) retention time = 0.59 min; [M+H]+ = 309 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.87 (s, 1H), 7.88 (dd, J = 9.4, 1.5 Hz, 1H), 7.81 (s, 1H), 7.64 (dd, J = 9.4, 0.7 Hz, 1H), 3.21 (s, 3H), 3.18 (s, 3H), 2.34 (s, 3H). Step 3: Preparation of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine
Figure imgf000207_0002
To a solution of (NE)-3-bromo-N-[1-(dimethylamino)ethylidene]imidazo[1,2-a]pyridine-6-carboxamide (150 mg, 0.485 mmol) in dimethylformamide (0.970 mL) was added 1-(4-fluoro-3- methoxyphenyl)hydrazine hydrochloride (118 mg, 0.582 mmol, 1.20 eq.). The reaction mixture was heated at 90 °C and stirred for 30 minutes, and then heated to 95 °C and stirred for an additional 3 hours. The reaction mixture was cooled and then water was added and the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl- 1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine as a brown solid. The product was used without further purification. LC/MS (method A) retention time = 0.85 min; [M+H]+ = 402 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.39 (dd, J = 1.6, 0.9 Hz, 1H), 7.81 (s, 1H), 7.63 - 7.68 (m, 1H), 7.44 (dd, J = 7.8, 2.4 Hz, 1H), 7.35 (dd, J = 11.1, 8.5 Hz, 1H), 7.26 (dd, J = 9.4, 1.5 Hz, 1H), 7.00 - 7.09 (m, 1H), 3.81 (s, 3H), 2.42 (s, 3H). Step 4: Preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 33) In a microwave test tube was added 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine (140 mg, 0.348 mmol) followed by 2-methoxycarbonylaminopyridine-5-boronic acid pinacol ester (143 mg, 0.487 mmol, 1.43 eq.), cesium carbonate (172 mg, 0.522 mmol, 1.50 eq.), 2-methyltetrahydrofuran (4.5 mL), water (1.5 mL) and tetrakis(triphenylphosphine)palladium(0) (20 mg, 0.017 mmol, 0.05 eq.). The reaction mixture was purged with argon and heated at 100 °C for 30 min under microwave irradiation. The solution was cooled to room temperature, water was added, and the solution was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, concentrated, and purified by silica gel column chromatography (dichloromethane/methanol) to afford methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-5-methyl-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a brown solid. LC/MS (method A) retention time = 0.72 min; [M+H]+ = 474 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.40 (s, 1H), 8.41 - 8.45 (m, 1H), 8.35 - 8.39 (m, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.84 (s, 1H), 7.76 (dd, J = 8.7, 2.2 Hz, 1H), 7.69 (dd, J = 9.4, 1.1 Hz, 1H), 7.39 (dd, J = 7.6, 2.5 Hz, 1H), 7.35 (dd, J = 9.4, 1.8 Hz, 1H), 7.29 (dd, J = 11.1, 8.5 Hz, 1H), 6.97 - 7.02 (m, 1H), 3.78 (s, 3H), 3.74 (s, 3H), 2.38 (s, 3H). Example 26: preparation of methyl N-[5-[6-[1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 43)
Figure imgf000208_0001
In a microwave vial charged with copper(I) chloride (113 mg, 1.12 mmol, 0.100 eq.), potassium carbonate (1.64 g, 11.8 mmol, 1.05 eq.), acetylacetone (0.290 mL, 2.80 mmol, 0.250 eq.) and NMP (2.24 mL) was added under argon imidazole (924 mg, 13.4 mmol, 1.20 eq.) and 1-bromo-4- fluorobenzene (1.26 mL, 11.2 mmol). The reaction mixture was heated at 120 °C and stirred. The reaction mixture was then cooled down to room temperature, mixed with saturated aqueous NaHCO3 solution and dichloromethane and stirred for 15 minutes at room temperature. The suspension was filtered through a pad of celite, and the filtrate was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/ethanol) to afford 1-(4-fluorophenyl)imidazole as a yellow liquid. LC/MS (method A) retention time = 0.22 min; [M+H]+ = 163 1H NMR (400 MHz, CDCl3, ppm) δ = ppm 7.78 (s, 1H), 7.33 - 7.44 (m, 2H), 7.12 - 7.27 (m, 4H). Step 2: Preparation of 3-bromo-6-[1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridine
Figure imgf000209_0001
To a solution of 1-(4-fluorophenyl)imidazole (300 mg, 1.85 mmol) in THF (2.50 mL) at 0°C under argon was added, dropwise, n-buthyllithium in hexane (2.50 mol/L, 0.890 mL, 2.22 mmol, 1.20 eq.). The reaction mixture was stirred for 30 minutes at 0 °C, then zinc chloride in methyl tetrahydrofuran (1.90 mol/L, 1.60 mL, 2.96 mmol, 1.60 eq.) was added and stirring continued for 30 minutes at room temperature. The reaction mixture was then concentrated to remove half of the solvent, and to that mixture was added dry toluene (1.85 mL), 3-bromo-6-iodoimidazo[1,2-a]pyridine (677 mg, 2.04 mmol, 1.10 eq.) and Pd(PPh3)4 (108 mg, 0.093 mmol, 0.05 eq.). The reaction mixture was heated at 100 °C and stirred overnight, then it was cooled to room temperature and stirred in a mixture of saturated aqueous NaHCO3 solution and ethyl acetate for 20 minutes. The mixture was then extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (cyclohexane/ethyl acetate/ethanol) to afford 3-bromo-6-[1-(4-fluorophenyl)imidazol-2- yl]imidazo[1,2-a]pyridine as a yellow solid. LC/MS (method A) retention time = 0.72 min; [M+H]+ = 357 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.07 (dd, J = 1.8, 1.1 Hz, 1H), 7.74 (s, 1H), 7.60 (dd, J = 9.4, 1.1 Hz, 1H), 7.58 (d, J = 1.1 Hz, 1H), 7.48 - 7.55 (m, 2H), 7.37 (t, J = 8.7 Hz, 2H), 7.29 (dd, J = 9.4, 1.8 Hz, 1H), 7.25 (d, J = 1.5 Hz, 1H). Step 3: Preparation of methyl N-[5-[6-[1-(4-fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 43) In a microwave test tube was added 3-bromo-6-[1-(4-fluorophenyl) imidazol-2-yl]imidazo[1,2-a]pyridine (80.0 mg, 0.220 mmol) followed by 2-methoxycarbonylaminopyridine-5-boronic acid, pinacol ester (92.0 mg, 0.310 mmol.1.40 eq.), cesium carbonate (110 mg, 0.340 mmol, 1.50 eq.), 2-methyltetrahydrofuran (2.90 mL), water (0.970 mL) and tetrakis(triphenylphosphine) palladium(0) (13.0 mg, 0.011 mmol, 0.0500 eq.). The reaction mixture was purged with argon and heated at 100 °C for 30 minutes under microwave irradiation. The solution was cooled to room temperature, water was added, and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/methanol) to afford methyl N-[5-[6-[1-(4- fluorophenyl)imidazol-2-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a white solid. LC/MS (method A) retention time = 0.67 min; [M+H]+ = 429 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.40 (s, 1H), 8.31 - 8.40 (m, 1H), 8.05 (d, J = 1.8 Hz, 1H), 7.91 - 7.96 (m, 1H), 7.77 (s, 1H), 7.61 - 7.69 (m, 2H), 7.51 (d, J = 1.1 Hz, 1H), 7.45 - 7.49 (m, 2H), 7.42 (dd, J = 9.3, 1.6 Hz, 1H), 7.27 - 7.34 (m, 2H), 7.21 (d, J = 1.5 Hz, 1H), 3.74 (s, 3H), 3.31 (s, 2H). Example 27: preparation of methyl N-[5-[6-[5-cyano-2-(4-fluorophenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 74)
Figure imgf000210_0001
(Compound 74) Step 1: Preparation of dimethyl 2-[(3-bromoimidazo[1,2-a]pyridine-6-carbonyl)amino]propanedioate
Figure imgf000210_0002
To a solution of 3-bromoimidazo[1,2-a]pyridine-6-carboxylic acid (500 mg, 2.03 mmol) in ethyl acetate (8.13 mL) was added dimethyl aminomalonate hydrochloride (500 mg, 2.64 mmol, 1.30 eq.) followed by N,N-diisopropylethylamine (1.79 mL, 10.2 mmol, 5.00 eq.) and propylphosphonic anhydride in ethyl acetate (50%, 2.42 mL, 4.07 mmol, 2.00 eq.). The reaction mixture was stirred for 2 hours at room temperature, then water was added, and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford dimethyl 2-[(3-bromoimidazo[1,2-a]pyridine-6- carbonyl)amino]propanedioate as a yellow solid. LC/MS (method A) retention time = 0.64 min; [M+H]+ = 370 1H NMR (400 MHz, DMSO-d6, ppm) δ = 9.80 (d, J = 7.6 Hz, 1H), 8.96 (dd, J = 1.8, 1.1 Hz, 1H), 7.85 (s, 1H), 7.75 - 7.80 (m, 1H), 7.70 - 7.75 (m, 2H), 5.45 (d, J = 7.6 Hz, 1H), 3.76 (s, 6H). Step 2: Preparation of methyl 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4-triazole-3- carboxylate
Figure imgf000211_0001
A solution of sodium nitrite (112 mg, 1.62 mmol, 1.20 eq.) in water (0.794 mL) was added dropwise to a mixture of 4-fluoroaniline (182 mg, 1.62 mmol, 1.20 eq.) and conc. HCl (0.397 mL) in acetic acid (1.17 mL) at 0 °C. The mixture was stirred for 15 minutes at 0 °C, then a solution of dimethyl 2-[(3- bromoimidazo[1,2-a]pyridine-6-carbonyl)amino]propanedioate (500 mg, 1.35 mmol) in acetone (4.50 mL) and a solution of potassium carbonate (1.88 g, 13.5 mmol, 10.0 eq.) in water (3.20 mL) were successively added at -10 °C. The resulting red mixture was stirred for 1 hour at 0 °C, then it was extracted with ethyl acetate. The combined organic layers were washed with a saturated aqueous NaHCO3 solution and water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in methanol (7.94 mL) and sodium methylate in methanol (5.40 mol/L, 0.0500 mL, 0.270 mmol, 0.200 eq.) was added. The reaction mixture was stirred for 1 hour at room temperature, the solid was filtered at 0 °C and washed with cold methanol to give the crude product methyl 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4-triazole-3-carboxylate as a yellow solid. The product was used in the next step without further purification. LC/MS (method A) retention time = 0.84 min; [M+H]+ = 416 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.41 (dd, J = 1.6, 0.9 Hz, 1H), 7.83 (s, 1H), 7.64 - 7.73 (m, 3H), 7.43 (t, J = 8.7 Hz, 2H), 7.29 (dd, J = 9.4, 1.8 Hz, 1H), 3.94 (s, 3H). Step 3: Preparation of 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4-triazole-3-
Figure imgf000211_0002
In a microwave vial was added methyl 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4- triazole-3-carboxylate (100 mg, 0.240 mmol) followed by ammonia in methanol (6.90 mL). The reaction mixture was stirred for 5 minutes at 80 °C and then 1 additional hour at room temperature. The volatiles were removed under reduced pressure and the residue was solubilized in dichloromethane (1.60 mL). Triethylamine (0.101 mL, 0.721 mmol, 3.00 eq.) was added to the solution, followed by a slow addition of trifluoro acetic anhydride (0.0675 mL, 0.481 mmol, 2.00 eq.). The reaction mixture was stirred for 30 minutes at room temperature, then it was quenched with a saturated aqueous NaHCO3 solution and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (cyclohexane/ethyl acetate) to afford 5-(3-bromoimidazo[1,2- a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4-triazole-3-carbonitrile as a white solid. LC/MS (method A) retention time = 0.96 min; [M+H]+ = 383 1H NMR (400 MHz, DMS-d6, ppm) δ = 8.41 (dd, J = 1.8, 1.1 Hz, 1H), 7.85 (s, 1H), 7.67 - 7.77 (m, 3H), 7.45 (t, J = 8.9 Hz, 2H), 7.29 (dd, J = 9.4, 1.5 Hz, 1H). Step 4: Preparation of methyl N-[5-[6-[5-cyano-2-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 74) In a microwave test tube was added 5-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1-(4-fluorophenyl)-1,2,4- triazole-3-carbonitrile (65.0 mg, 0.170 mmol) followed by 2-methoxycarbonylaminopyridine-5-boronic acid, pinacol ester (70.0 mg, 0.240 mmol, 1.40 eq.), cesium carbonate (84.0 mg, 0.250 mmol, 1.50 eq.), 2-methyltetrahydrofuran (2.20 mL), water (0.730 mL) and tetrakis(triphenylphosphine) palladium(0) (10 mg, 0.009 mmol, 0.05 eq.). The reaction mixture was purged with argon and heated at 100 °C for 30 minutes under microwave irradiation. The solution was cooled to room temperature, water was added, and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (cyclohexane/[ethyl acetate/ethanol; 3/1]) first and then via a second flash chromatography over silica gel (dichloromethane/methanol) to afford methyl N-[5-[6- [5-cyano-2-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a yellow solid. LC/MS (method A) retention time = 0.84 min; [M+H]+ = 455 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.44 (s, 1H), 8.40 - 8.42 (m, 1H), 8.38 - 8.40 (m, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.88 (s, 1H), 7.66 - 7.77 (m, 4H), 7.36 - 7.44 (m, 3H), 3.74 (s, 3H). Example 28: preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 4) (Compound 4) Step 1: Preparation of (NE)-3-bromo-N-(dimethylaminomethylene)imidazo[1,2-a]pyridine-6- carboxamide
Figure imgf000213_0001
To a suspension of 3-bromoimidazo[1,2-a]pyridine-6-carboxamide (see synthetic example 25, step 1; 0.82 g, 3.41 mmol) in N,N-dimethylformamide dimethyl acetal (0.623 g, 0.695 mL, 5.12 mmol) was added acetic acid (0.041 g, 0.039 mL, 0.683 mmol). The reaction mixture was heated to 95 °C and stirred for 10 min. The reaction mixture was then cooled to room temperature, water was added and the precipitate was filtered to give (NE)-3-bromo-N-(dimethylaminomethylene)imidazo[1,2-a]pyridine-6- carboxamide as a white solid. The product was used for the next step without further purification. LC/MS (method A) retention time = 0.59 min; [M+H]+ = 295 1H NMR (400 MHz, DMSO-d6, ppm) δ = 9.00 - 9.04 (m, 1H), 8.69 (s, 1H), 7.95 (dd, J = 9.4, 1.8 Hz, 1H), 7.82 (s, 1H), 7.66 (dd, J = 9.3, 0.9 Hz, 1H), 3.24 (s, 3H), 3.19 (s, 3H). Step 2: Preparation of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridine (Intermediate I-1)
Figure imgf000213_0002
(Intermediate I-1) To a solution of (NE)-3-bromo-N-(dimethylaminomethylene)imidazo[1,2-a]pyridine-6-carboxamide (750 mg, 2.54 mmol) in dimethylformamide (25.4 mL) was added 1-(4-fluoro-3-methoxyphenyl)hydrazine hydrochloride (618 mg, 3.05 mmol, 1.20 eq.). The reaction mixture was heated at 90 °C and stirred overnight. After cooling down to room temperature, water was added, and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (cyclohexane/ethyl acetate) to afford 3-bromo-6-[2-(4-fluoro-3-methoxy- phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine. LC/MS (method A) retention time = 0.82 min; [M+H]+ = 388 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.38 - 8.42 (m, 1H), 8.33 (s, 1H), 7.82 (s, 1H), 7.69 (d, J = 9.4 Hz, 1H), 7.47 (dd, J = 7.8, 2.4 Hz, 1H), 7.38 (dd, J = 11.1, 8.5 Hz, 1H), 7.32 (dd, J = 9.4, 1.8 Hz, 1H), 7.05 - 7.11 (m, 1H), 3.81 (s, 3H). Step 3: Preparation of methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 4) In a microwave test tube 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridine (Intermediate I-1, 785 mg, 1.92 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-2-pyridyl]carbamate (748 mg, 2.69 mmol, 1.40 eq.) were dissolved in 2- methyltetrahydrofuran (11.5 mL) and water (3.84 mL). Then cesium carbonate (939 mg, 2.88 mmol, 1.50 eq.) was added and the mixture was purged with a stream of argon for 5 minutes before tetrakis(triphenylphosphine) palladium(0) (114 mg, 0.096 mmol, 0.05 eq.) was added. The mixture heated under microwave irradiation at 100 °C for 30 minutes, then it was cooled to room temperature, water was added, and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (ethyl acetate/ethanol in cyclohexane) to afford methyl N-[5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate. LC/MS (method A) retention time = 0.71 min; [M+H]+ = 460 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.40 (s, 1H), 8.41 (dd, J=2.5, 0.7 Hz, 1 H), 8.36 - 8.39 (m, 1 H), 8.28 (s, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.84 (s, 1H), 7.70 - 7.77 (m, 2H), 7.39 - 7.45 (m, 2H), 7.31 (dd, J = 11.3, 8.7 Hz, 1H), 6.99 - 7.09 (m, 1H), 3.78 (s, 3H), 3.74 (s, 3H). Example 29: preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (compound 75)
Figure imgf000214_0001
(Compound 75) Step 1: Preparation of 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole N
Figure imgf000215_0001
To 3-bromoimidazo[1,2-a]pyridine-6-carbohydrazide (see synthetic example 20, step 1; 360 mg, 1.41 mmol) was added triethyl orthoformate (2.40 mL, 14.1 mmol, 10.0 eq.) and the reaction mixture was stirred overnight at 140 °C. The reaction mixture was cooled and then 1,8-diazabicyclo[5.4.0]undec-7- ene (0.258 mL, 1.69 mmol, 1.20 eq.) was added and stirring continued at 140 °C for 15 minutes. The reaction mixture was cooled down to room temperature, the precipitate was filtered and washed with ethanol to give the desired compound 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole. The filtrate was concentrated and purified by flash chromatography over silica gel (cyclohexane/[ethyl acetate/ethanol; 3/1]) to afford more of the desired compound 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)- 1,3,4-oxadiazole as beige solid. LC/MS (method A) retention time = 0.56 min; [M+H]+ = 265 1H NMR (400 MHz, DMSO-d6, ppm) δ = 9.44 (s, 1H), 8.84 (s, 1H), 7.90 (s, 1H), 7.87 (app br s, 2H). Step 2: Preparation of 3-bromo-6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine
Figure imgf000215_0002
To a solution of 2-(3-bromoimidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole (160 mg, 0.604 mmol) in acetic acid (2.01 mL) was added 4-fluoroaniline (0.289 mL, 3.02 mmol, 5.00 eq.). The reaction mixture was heated at 120 °C and stirred for 4 hours, then it was cooled down to room temperature, saturated aqueous aq. NaHCO3 solution was slowly added, and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel (cyclohexane/ethyl acetate/ethanol) to afford 3-bromo-6-[4-(4-fluorophenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridine as a brown solid. LC/MS (method A) retention time = 0.70 min; [M+H]+ = 358 1H NMR (400 MHz, CDCl3, ppm) δ = 8.45 (br s, 1H), 8.40 (s, 1H), 7.65 - 7.73 (m, 2H), 7.32 - 7.39 (m, 2H), 7.24 - 7.31 (m, 3H). Step 3: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 75) In a microwave test tube 3-bromo-6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine (90.0 mg, 0.251 mmol) and 2-methoxycarbonylaminopyridine-5-boronic acid pinacol ester (101 mg, 0.352 mmol, 1.40 eq.) were dissolved in 1,4-dioxane (7.5 mL) and water (2.5 mL). Cesium carbonate (124 mg, 0.377 mmol, 1.50 eq.) was added and the mixture was purged with a stream of argon for 5 minutes before tetrakis(triphenylphosphine) palladium(0) (15 mg, 0.013 mmol, 0.05 eq.) was added. The reaction mixture was heated under microwave irradiation at 100 °C for 30 minutes, then it was cooled at room temperature, diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (cyclohexane/[ethyl acetate/EtOH; 3/1]) to afford methyl N-[5-[6-[4-(4-fluorophenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate as a brown solid. LC/MS (method A) retention time = 0.62 min; [M+H]+ = 430 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.42 (s, 1H), 8.89 (s, 1H), 8.33 - 8.45 (m, 1H), 8.19 - 8.28 (m, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.83 (s, 1H), 7.68 - 7.74 (m, 2H), 7.54 - 7.62 (m, 2H), 7.42 (dd, J = 9.3, 1.6 Hz, 1H), 7.35 (t, J = 8.7 Hz, 2H), 3.74 (s, 3H), 3.31 (s, 3H). Example 30: preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridin- 3-yl]-2-pyridyl]carbamate (compound 76)
Figure imgf000216_0001
To a solution of methyl 3-bromoimidazo[1,2-a]pyridine-6-carboxylate (1.00 g, 3.84 mmol) and N,O- dimethylhydroxylamine hydrochloride (574 mg, 5.76 mmol, 1.50 eq.) in THF (12.8 mL) at 0 °C under argon was added methyl magnesium bromide in methyltetrahydrofuran (5.40 mL, 17.3 mmol). The reaction mixture was stirred for 5 minutes at 0 °C, then saturated aqueous NH3Cl solution was slowly added, and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel (cyclohexane/ethyl acetate) to afford 1-(3- bromoimidazo[1,2-a]pyridin-6-yl)ethanone as beige solid. LC/MS (method A) retention time = 0.60 min; [M+H]+ = 239 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.83 - 8.93 (m, 1H), 7.87 (s, 1H), 7.77 (dd, J = 9.4, 1.8 Hz, 1H), 7.71 (d, J = 9.4 Hz, 1H), 2.69 (s,3 H). Step 2: Preparation of 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-3-(dimethylamino)prop-2-en-1-one To a solution of 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)ethenone (110 mg, 0.460 mmol) in N,N- dimethylformamide dimethyl acetal (0.094 mL, 0.69 mmol, 1.5 eq.) was added acetic acid (0.0053 mL, 0.092 mmol, 0.2 eq.). The reaction mixture was heated at 95 °C and stirred for 1 hour, then water was added, and the solution was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 1-(3- bromoimidazo[1,2-a]pyridin-6-yl)-3-(dimethylamino)prop-2-en-1-one as a brown solid. The compound was used for the next step without further purification. LC/MS (method A) retention time = 0.55 min; [M+H]+ = 294 1H NMR (400 MHz, CDCl3, ppm) δ = 8.75 - 8.78 (m, 1H), 7.91 (d, J = 12.4 Hz, 1H), 7.78 (dd, J = 9.4, 1.8 Hz, 1H), 7.67 (s, 1H), 7.64 (dd, J = 9.4, 0.7 Hz, 1H), 5.68 (d, J = 12.4 Hz, 1H), 3.22 (br s, 3H), 3.00 (br s, 3H). Step 3: Preparation of 3-bromo-6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridine
Figure imgf000217_0001
To a solution of 1-(3-bromoimidazo[1,2-a]pyridin-6-yl)-3-(dimethylamino)prop-2-en-1-one (130 mg, 0.442 mmol) in dimethylformamide (0.88 mL) was added 4-fluorophenylhydrazine hydrochloride (89 mg, 0.53 mmol, 1.2 eq.). The reaction mixture was heated at 90 °C and stirred for 90 minutes, it was then cooled down to room temperature, water was added, and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel (cyclohexane/[ethyl acetate/ethanol; 3/1]) to afford 3-bromo-6-[2-(4-fluorophenyl)pyrazol-3- yl]imidazo[1,2-a]pyridine. LC/MS (method A) retention time = 0.85 min; [M+H]+ = 357 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.10 (dd, J = 1.8, 1.1 Hz, 1H), 7.78 (d, J = 1.8 Hz, 1H), 7.68 (s, 1H), 7.61 (dd, J = 9.3, 0.9 Hz, 1H), 7.31 - 7.28 (m, 2H), 7.07 - 7.14 (m, 2H), 7.03 (dd, J = 9.4, 1.8 Hz, 1H), 6.64 (d, J = 1.8 Hz, 1H). Step 4: Preparation of methyl N-[5-[6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (Compound 76) In a microwave test tube was added 3-bromo-6-[2-(4-fluorophenyl)pyrazol-3-yl]imidazo[1,2-a]pyridine (110 mg, 0.308 mmol) followed by 2-methoxycarbonylaminopyridine-5-boronic acid pinacol ester (124 mg, 0.431 mmol, 1.40 eq.), cesium carbonate (152 mg, 0.462 mmol, 1.5 eq.), 1,4-dioxane (9.2 mL), water (3.1 mL) and tetrakis(triphenylphosphine) palladium(0) (18.0 mg, 0.0154 mmol, 0.0500 eq.). The reaction mixture was purged with argon and heated at 100 °C under microwave irradiation for 30 minutes. The reaction mixture was then cooled, water was added and the solution was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (dichloromethane/methanol) to afford methyl N-[5-[6-[2-(4-fluorophenyl)pyrazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a beige solid. LC/MS (method A) retention time = 0.70 min; [M+H]+ = 429 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.41 (s, 1H), 8.48 (d, J = 1.8 Hz, 1H), 8.32 (s, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.87 (dd, J = 8.7, 2.5 Hz, 1H), 7.82 (s, 1H), 7.78 (d, J = 1.8 Hz, 1H), 7.60 - 7.65 (m, 1H), 7.42 - 7.49 (m, 2H), 7.28 (t, J = 8.7 Hz, 2H), 7.06 (dd, J = 9.3, 1.6 Hz, 1H), 6.84 (d, J = 1.8 Hz, 1H), 3.73 (s, 3H). Example 31: preparation of methyl N-[5-[6-[4-(4-fluoro-3-methyl-phenyl)-5-methyl-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 5)
Figure imgf000218_0001
A solution of 2-amino-5-bromo-3-methylpyridine (2.0 g, 10.7 mmol) in ethanol (42.8 mL) was stirred under nitrogen atmosphere. Then chloroacetaldehyde solution (2.33 g, 13.37 mmol, 1.89 mL, 1.25 eq.) was added. The resulting reaction mixture was refluxed at 100 °C for 5 hours and then at 55 °C overnight. The reaction mixture was concentrated. Then ethyl acetate was added.The suspension was filtered and the solid collected and dried, to afford 6-bromo-8-methylimidazo[1,2-a]pyridine as a brown solid. LC/MS (method B) retention time = 0.66 min; [M+H] += 211 Step 2: Preparation of methyl 8-methylimidazo[1,2-a]pyridine-6-carboxylate To a mixture of 6-bromo-8-methyl-imidazo[1,2-a]pyridine (9.00 g, 42.6 mmol) in methanol (100.0 mL) was added 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1.73 g, 2.13 mmol, 0.05 eq.) and N,N-diethylethanamine (12.9 g, 128 mmol, 3.00 eq.). The bomb was then flushed with carbon monoxide, sealed, and pressurized to 2.5 MPa with carbon monoxide. The reaction was stirred at 100 °C for 8 hours. The vessel was then cooled to room temperature and the pressure released. The reaction mixture was concentrated to dryness and purified by silica gel column chromatography (eluting with dichloromethane/MeOH) to obtain the methyl 8-methylimidazo[1,2- a]pyridine-6-carboxylate as a brown solid. LC/MS (method B) retention time = 0.19 min; [M+H] += 191 1H-NMR (400 MHz, DMSO-d6, ppm) δ = 9.20 (s, 1H), 8.10 (s, 1H), 7.65 (s, 1H), 7.45 (s, 1H), 3.88 (s, 3H), 2.52 (s, 3H). Step 3: Preparation of methyl 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboxylate
Figure imgf000219_0001
To a mixture methyl 8-methylimidazo[1,2-a]pyridine-6-carboxylate (0.50 g, 2.6 mmol) in acetonitrile (13 mL) under an atmosphere of argon at room temperature was added N-bromosuccinimide (0.53 g, 2.9 mmol, 1.1 eq.) The reaction mixture was stirred for 45 min and then quenched with 1 M aqueous sodium sulfite solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 3-bromo-8- methyl-imidazo[1,2-a]pyridine-6-carboxylate as a pale beige solid. 1H NMR (400 MHz, CDCl3, ppm) δ = 8.78 (d, J = 0.7 Hz, 1H), 7.69 (s, 1H), 7.58 - 7.65 (m, 1H), 3.99 (s, 3H), 2.65 (s, 3H) Step 4: Preparation of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carbohydrazide (Intermediate I-2)
Figure imgf000219_0002
(Intermediate I-2) To a solution of methyl 3-bromoimidazo[1,2-a]pyridine-6-carboxylate (1.00 g, 3.80 mmol) in methanol (5.43 mL) was added hydrazine hydrate (0.226 mL, 4.56 mmol, 1.20 eq.). The reaction mixture was stirred overnight at 70 °C, then it was cooled down to room temperature, water was added and the precipitate was filtered and washed with water to afford 3-bromoimidazo[1,2-a]pyridine-6- carbohydrazide as a white solid. LC/MS (method B) retention time = 0.19 min; [M+H] += 255 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.07 (br s, 1H), 8.79 (s, 1H), 7.82 (s, 1H), 7.72 - 7.77 (m, 1H), 7.67 - 7.72 (m, 1H), 4.58 (br s, 2H). Step 5: Preparation of 2-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole (Intermediate I-3)
Figure imgf000220_0001
(Intermediate I-3) A mixture of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carbohydrazide (Intermediate I-2, 9.4 g, 35 mmol) and triethyl orthoacetate (58 g, 65 mL, 350 mmol, 10 eq.) was stirred for 3 hours at 130 °C.1,8- diazabicyclo[5.4.0]undec-7-ene (6.5 g, 6.4 mL, 42 mmol, 1.2 eq.) was then added. The reaction mixture was heated at 130 °C for 2 hours, then cooled down to room temperature. Cold water was added, followed by ethyl acetate. The aqueous layer was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. Triturating and washings with pentane and tert-butyl methyl ether afforded 2-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4- oxadiazole (Intermediate I-3) as a light brown solid. LC/MS (method B) retention time = 1.28 min; [M+H] += 295 1H NMR (400 MHz, DMSO-d6, ppm) δ = 2.59 (s, 3 H), 2.63 (s, 3 H), 7.70 (s, 1 H), 7.85 (s, 1 H), 8.62 (s, 1 H). Step 6: Preparation of 5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin- 2-amine
Figure imgf000220_0002
In a microwave vial 2-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole (Intermediate I-3, 0.34 g, 1.16 mmol), and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2- amine (0.383 g, 1.74 mmol, 1.50 eq.) were dissolved in acetonitrile (9.28 mL). Then sodium carbonate (0.37 g, 3.48 mmol, 3.00 eq.) dissolved in water was added. The resulting reaction mixture was degassed with nitrogen for 15 min. Then chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'- biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.094 g, 0.116 mmol, 0.10 eq.) was added. The reaction mixture was irradiated with microwave radiation for 1 hour, then filtered through celite and concentrated under reduced pressure. The crude mixture was washed with pentane and tert-butyl methyl ether to afford 5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2- amine as brown solid. LC/MS (method B) retention time = 1.18 min; [M+H] += 307 Step 7: Preparation of methyl N-[5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate
Figure imgf000221_0001
To a solution of 5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]pyridin-2-amine (300 mg, 0.98 mmol) in dichloromethane (6 mL) in acetonitrile (4 mL) was added pyridine (316.2 mg, 0.323 mL, 3.92 mmol, 4.00 eq.), followed by methyl carbonochloridate (0.229 mL, 2.94 mmol, 3.00 eq.). the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and purified by flash chromatography on neutral alumina (eluting 15-20% methanol in ethyl acetate) to afford methyl N-[5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate. LC/MS (method B) retention time = 0.67 min; [M+H] += 365 Step 8: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methyl-phenyl)-5-methyl-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 5) A solution of methyl N-[5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (0.06 g, 0.1 mmol) in acetic acid (0.3 mL) was treated with 4-fluoro-3-methyl-aniline (0.04 g, 0.3 mmol, 3 eq.) and the mixture was heated and stirred at 120 °C for 1 hour. The reaction mixture was cooled down to room temperature and concentrated under reduced pressure. The crude residue was purified by chromatography on neutral alumina (eluting 5-10% methanol in ethyl acetate) to afford methyl N-[5-[6-[4-(4-fluoro-3-methyl-phenyl)-5-methyl-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate as a yellow gum. LC/MS (method B) retention time = 0.17 min; [M+H] += 472 1H NMR (400 MHz, CD3OD, ppm) δ = 8.21 (dd, 1 H) 8.06 (dd, 1 H) 7.85 (d, 1 H) 7.67 (s, 1 H) 7.53- 7.59 (m, 2 H) 7.37 (d, 1 H) 7.19 - 7.28 (m, 2 H) 3.84 (s, 3 H) 2.59 (s, 3 H) 2.32(s, 3H) 2.29 (s, 3H) Example 32: Preparation of methyl N-[5-[8-cyclopropyl-6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 2) (Compound 2) Step 1: Preparation of methyl 8-bromoimidazo[1,2-a]pyridine-6-carboxylate
Figure imgf000222_0001
A solution of methyl 6-amino-5-bromonicotinate (4.00 g, 21.4 mmol) in ethanol (86 mL) was stirred under nitrogen atmosphere. Then chloroacetaldehyde solution (26.7 mmol, 3.78 mL, 1.25 eq.) was added. The resulting reaction mixture was refluxed at 100 °C for 5 hours and then at 55 °C overnight. The reaction mixture was concentrated, then ethyl acetate was added. The suspension was filtered, the solid was collected and dried to get methyl 8-bromoimidazo[1,2-a]pyridine-6-carboxylate as a brown solid. LC/MS (method B) retention time = 0.59 min; [M+H] += 257 Step 2: Preparation of methyl 8-cyclopropylimidazo[1,2-a]pyridine-6-carboxylate
Figure imgf000222_0002
To a solution of methyl 8-bromoimidazo[1,2-a]pyridine-6-carboxylate (5.00 g, 17.6 mmol) in cyclopentyl methyl ether (50 mL) were added cyclopropylboronic acid;hydrate (2.89 g, 26.4 mmol, 1.50 eq.) and potassium carbonate (6.10 g, 44.0 mmol, 2.50 eq.). The mixture was degassed with nitrogen for 30 min. [1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (0.645 g, 0.88 mmol, 0.05 eq.) was then added. The resulting mixture was stirred at 85 °C overnight. Then additional cyclopropylboronic acid;hydrate (2.89 g, 26.4 mmol, 1.50 eq.) and [1,1'-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (0.645 g, 0.88 mmol, 0.05 eq.) were added. The reaction mixture was cooled down to room temperature and then water was added. The aqueous layer was extracted ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified over a silica gel cartridge (cyclohexane/ethyl acetate, 3:2) to afford methyl 8-cyclopropylimidazo[1,2-a]pyridine-6-carboxylate as brown solid. LC/MS (method B) retention time = 0.37 min; [M+H] += 217 1H NMR (400 MHz, CDCl3, ppm) δ = 0.96 - 1.07 (m, 2 H) 1.13 - 1.23 (m, 2 H) 2.51 - 2.68 (m, 1 H) 3.96 (s, 3 H) 7.22 - 7.28 (m, 1 H) 7.64 - 7.71 (m, 1 H) 7.72 - 7.77 (m, 1 H) 8.70 - 8.89 (m, 1 H) Step 3: Preparation of 8-cyclopropylimidazo[1,2-a]pyridine-6-carbohydrazide
Figure imgf000223_0001
To a solution of methyl 8-cyclopropylimidazo[1,2-a]pyridine-6-carboxylate (1.99 g, 9.20 mmol) in methanol (13.1 mL) was added hydrazine hydrate (1.46 mL, 46.0 mmol, 5 eq.). The reaction mixture was stirred at 75 °C for 5 hours, then at 45 °C for 18 hours. The reaction mixture was concentrated and the crude residue was used as such in the next step. LC/MS (method B) retention time = 0.14 min; [M+H] += 217 Step 4: Preparation of 2-(8-cyclopropylimidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole
Figure imgf000223_0002
To a mixture of 8-cyclopropylimidazo[1,2-a]pyridine-6-carbohydrazide (1.9 g, 8.8 mmol) and diethoxymethoxyethane (16.5 ml, 88 mmol, 10 eq.) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (1.6 mL, 11 mmol, 1.2 eq.). The reaction mixture was stirred for overnight at 120 °C. The reaction mixture was cooled down to room temperature and then water was added. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified over a silica gel cartridge (eluting cyclohexane/ethyl acetate, 3:7) to afford 2-(8-cyclopropylimidazo[1,2-a]pyridin-6-yl)- 1,3,4-oxadiazole as white solid. LC/MS (method B) retention time = 0.14 min; [M+H] += 227 Step 5: Preparation of 2-(3-bromo-8-cyclopropyl-imidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole
Figure imgf000223_0003
To a solution of 2-(8-cyclopropylimidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole (1.14 g, 5.04 mmol) in acetonitrile (11.4 mL) was added N-bromosuccinimide (0.997 g, 5.54 mmol, 1.10 eq.). The reaction mixture was stirred at room temperature for 90 min, then water was added. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with sodium thiosulphate pentahydrate, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude was purified by flash chromatography over silical gel (eluting cyclohexane/ethyl acetate, 8:2) to afford ethyl acetate 2-(3-bromo-8-cyclopropyl-imidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole as a yellow solid. LC/MS (method B) retention time = 0.66 min; [M+H] += 307 Step 6: Preparation of methyl N-[5-[8-cyclopropyl-6-(1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate
Figure imgf000224_0001
To a solution of 2-(3-bromo-8-cyclopropyl-imidazo[1,2-a]pyridin-6-yl)-1,3,4-oxadiazole (200 mg, 0.49 mmol) in acetonitrile (3.93 mL) were added 2-methoxycarbonylaminopyridine-5-boronic acid, pinacol ester (0.187 g, 0.64 mmol, 1.30 eq.), water (1.97 mL) and sodium carbonate (0.156 g, 1.47 mmol, 3.00 eq.). The mixture was degassed with nitrogen for 10 min. Then chloro(2-dicyclohexylphosphino-2',4',6'- triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.0399 g, 0.0490 mmol, 0.100 eq.) was added. The mixture was irradiated with microwave radiations at 100 °C for 2 hours. The reaction mixture was cooled down to room temperature, then water was added. The aqueous layer was extracted ethyl acetate, the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified via reverse phase chromatography (eluting water/acetonitrile, 3:7) to afford methyl N-[5-[8-cyclopropyl-6-(1,3,4-oxadiazol- 2-yl)imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as white solid . LC/MS (method B) retention time = 0.35 min; [M+H] += 377 1H NMR (400 MHz, CD3OD, ppm) δ = 1.12 - 1.21 (m, 4 H), 2.56 - 2.66 (m, 1 H), 3.73 (s, 3 H), 7.37 (s, 1 H), 7.90 (s, 1 H), 8.05 (d, J = 8.56 Hz, 1 H), 8.13 - 8.21 (m, 1 H), 8.60 (d, J = 1.96 Hz, 1 H), 8.77 (s, 1 H), 9.38 (s, 1 H), 10.51 (s, 1 H) Step 7: Preparation of methyl N-[5-[8-cyclopropyl-6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 2) To a solution of methyl N-[5-[8-cyclopropyl-6-(1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (0.030 g, 0.079 mmol) in acetic acid (0.28 mL) was added 4-fluoro-2-methoxyaniline (0.0337 g, 0.239 mmol, 3.00 eq.). The resulting reaction mixture was heated at 120 °C for 1 hour. The reaction mixture was concentrated under reduced pressure. The crude was purified over silica gel (ethyl acetate/methanol, 95:5) to afford methyl N-[5-[8-cyclopropyl-6-[4-(4-fluoro-3-methoxy-phenyl)-1,2,4- triazol-3-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as brown solid. LC/MS (method B) retention time = 0.90 min; [M+H] += 500 1H NMR (400 MHz, DMSO-d6, ppm) δ = 3.74 (s, 3 H), 3.78 (s, 3 H), 6.93 (d, 1 H), 7.31 (t, 1 H), 7.46 (dd, 1 H), 7.56 (1H, d), 7.72 (d, 1 H), 7.79 (s, 1 H), 7.96 (d, 1 H), 8.11 (d, 1 H), 8.40 (d, 1 H), 8.87 (s, 1 H), 10.44 (s, 1 H) Example 33: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-5-methyl-1,2,4-triazol-3-yl]-8- methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 6)
Figure imgf000225_0001
(Compound 6) Step 1: Preparation of methyl N-[5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate
Figure imgf000225_0002
To a mixture of 2-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-methyl-1,3,4-oxadiazole (Intermediate I-3, 0.050 g), 2-methoxycarbonylaminopyridine-5-boronic acid, pinacol ester (1.0 eq., 0.050 g) and potassium carbonate (0.17 g, 7.0 eq.) in toluene (1.7 mL)/ EtOH (0.60 mL)/ Water (0.34 mL) under an argon atmosphere was added Pd(PPh3)4 (0.020 g, 0.10 eq.). The mixture was heated and stirred at 80 °C for 50 hours. The reaction mixture was then cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with saturated aqueous bicarbonate solution and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford methyl N-[5-[8- methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a beige solid. LC/MS (method B) retention time = 0.19 min; [M+H] += 365 Step 2: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-5-methyl-1,2,4-triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 6) A solution of methyl N-[5-[8-methyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate (0.050 g, 0.10 mmol, 1.0 eq.) in acetic acid (0.3 mL) was treated with 4-fluoroaniline (0.030 g, 0.30 mmol, 3.0 eq.) and the resulting mixture was heated at 120 °C for 1 hour. The reaction mixture was cooled down to room temperature and concentrated under reduced pressure. The crude residue was purified on neutral alumina (eluting with ethyl acetate/methanol) to afford methyl N-[5-[6-[4- (4-fluoro-3-methyl-phenyl)-5-methyl-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate as a gummy mass. LC/MS (method B) retention time = 0.16 min; [M+H] += 458 1H NMR (400 MHz, CD3OD, ppm) δ = 8.23 (d, 1 H) 8.05 (d, 1 H) 7.93 (s, 1 H) 7.69 (s, 1 H) 7.59 (dd, 1 H) 7.43 - 7.53 (m, 3 H) 7.24 - 7.41 (m, 2 H) 3.84 (s, 3 H) 2.57 (s, 3 H) 2.34 (s, 3 H) Example 34: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-(methoxymethyl)- 1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 7)
Figure imgf000226_0001
(Compound 7) Step 1: Preparation of 2-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-(methoxymethyl)-1,3,4- oxadiazole
Figure imgf000226_0002
To a solution of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carbohydrazide (Intermediate I-2, 0.50 g, 2.0 mmol) was added toluene (7 mL) 1,1,1,2-tetramethoxyethane (0.30 g, 0.30 mL, 2.0 mmol) and the reaction mixture was stirred for 1h at 100 °C. The reaction mixture was concentrated under vacuo, the residue was washed with pentane and tert-butyl methyl ether, dried under vacuo to afford 2-(3-bromo- 8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-(methoxymethyl)-1,3,4-oxadiazole as an off white solid. LC/MS (method B) retention time = 1.05 min; [M+H]+ = 325 Step 2: Preparation of 3-bromo-6-[4-(4-fluoro-3-methoxy-phenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]- 8-methyl-imidazo[1,2-a]pyridine A solution of 2-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-5-(methoxymethyl)-1,3,4-oxadiazole (0.27 g, 0.84 mmol) in acetic acid (2.9 mL) was treated with 4-fluoro-3-methoxy-aniline (0.35 g, 2.52 mmol, 3.0 eq.) and the mixture was heated and stirred at 120 °C for 1 hour. The reaction mixture was cooled down to room temperature and concentrated under reduced pressure. The residue was purified on neutral alumina (eluting methanol/ethyl acetate) to afford 3-bromo-6-[4-(4-fluoro-3-methoxy-phenyl)-5- (methoxymethyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridine as a solid. LC/MS (method B) retention time = 0.99 min; [M+H] += 447 Step 3: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5-(methoxymethyl)-1,2,4-triazol-3- yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 7) A mixture of 3-bromo-6-[4-(4-fluoro-3-methoxy-phenyl)-5-(methoxymethyl)-1,2,4-triazol-3-yl]-8-methyl- imidazo[1,2-a]pyridine (0.30 g, 0.67 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)-2-pyridyl]carbamate (0.28 g, 1.00 mmol, 1.5 eq.) was dissolved in acetonitrile (5.37 mL). Sodium carbonate (0.213 g, 2.02 mmol, 3.00 eq.) dissolved in water (2.68 mL) was added. The resulting reaction mixture was purged with nitrogen for 15 mins. Chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'- biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.054 g, 0.067 mmol, 0.10 eq.) was added. The reaction mixture was irradiated with microwave radiation for 1 hour at 100 °C. The reaction mixture was filtered through celite, and the filtrate was concentrate. The crude residue was purified by flash chromatography on neutral alumina (5-10% methanol in ethyl acetate) to afford an off white solid, which was further washed with tert-butyl methyl ether to afford methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)- 5-(methoxymethyl)-1,2,4-triazol-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off white solid LC/MS (method B) retention time = 0.93 min; [M+H] += 518.2 1H NMR (400 MHz, CD3OD, ppm) δ = 8.23 (d, 1 H), 8.07 (d, 1 H), 7.94 (s, 1 H), 7.69 (s, 1 H), 7.55 - 7.60 (m, 2 H), 7.31(dd, 1 H), 7.23 (dd, 1 H), 6.92 - 6.97 (m, 1 H), 4.48 (s, 2 H), 3.84 (s, 3 H), 3.80 (s, 3 H), 3.30 (s, 3 H), 2.60 (s, 3 H) Example 35: Preparation of methyl N-[5-[6-[1-(4-fluoro-3-methoxy-phenyl)imidazol-2-yl]-8- methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 8) To a stirred solution of 5-iodo-3-methyl-pyridin-2-amine (20.0 g, 85.5 mmol) in EtOH (200 mL) was added 2-chloroacetaldehyde (30.2 g, 385 mmol) and sodium hydrogen carbonate (12.9 g, 154 mmol) at room temperature. The reaction mixture was stirred at 80 °C for 16 hours. The reaction mixture was then concentrated under reduced pressure. Saturated aqueous NaHCO3 and dichloromethane were added. The aqueous layer was extracted with dichloromethane, the combined organic phases were dried with sodium sulfate, filtered and concentrated under reduced pressure. The residual was purified by silica gel column chromatography (eluting with ethyl acetate/petroleum ether, 0% to 75%) to afford 6-iodo-8-methyl-imidazo[1,2-a]pyridine as a yellow solid. LC/MS (method A) retention time = 0.52 min; [M+H] += 259.1 1H NMR (400 MHz, DMSO-d6, ppm) δ = 8.78 (s, 1H), 7.86 (s, 1H), 7.49 (s, 1H), 7.26 (s, 1H), 2.51 (s, 3H) Step 2: Preparation of 3-bromo-6-iodo-8-methyl-imidazo[1,2-a]pyridine
Figure imgf000228_0001
To a solution of 6-iodo-8-methyl-imidazo[1,2-a]pyridine (Intermediate I-4, 2.00 g, 7.75 mmol) in dimethylformamide (50.0 mL) was added 1-bromopyrrolidine-2,5-dione (1.52 g, 8.53 mmol). The mixture was stirred at room temperature for 12 hours. Then the resulting mixture was diluted with water (50 mL) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel column chromatography (eluting with ethyl acetate /petroleum ether, 0% to 35%) to give 3-bromo-6-iodo-8- methyl-imidazo[1,2-a]pyridine as a yellow solid. LC/MS (method A) retention time = 1.35 min; [M+H] += 338 Step 3: Preparation of 1-(4-fluoro-3-methoxy-phenyl)imidazole
Figure imgf000229_0001
To a solution of 4-bromo-1-fluoro-2-methoxy-benzene (5.00 g, 24.4 mmol) in 1-methylpyrrolidin-2-one (50.0 mL) was added imidazole (1.83 g, 26.8 mmol), K2CO3 (3.53 g, 25.6 mmol, 1.10 eq.), iodocopper (0.464 g, 2.44 mmol, 0.10 eq.) and pentane-2,4-dione (0.610 g, 6.10 mmol, 0.25 eq.) at 25 °C. The mixture was heated at 120 °C for 12 hours. Then the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel column chromatography (eluting with dichloromethane/MeOH, 0% to 4%) to give 1-(4-fluoro-3-methoxy-phenyl)imidazole as a colorless oil. LC/MS (method A) retention time = min; [M+H] += 193 Step 4: Preparation of 3-bromo-6-[1-(4-fluoro-3-methoxy-phenyl)imidazol-2-yl]-8-methyl-imidazo[1,2- a]pyridine
Figure imgf000229_0002
To a solution of 1-(4-fluoro-3-methoxy-phenyl)imidazole (0.700 g, 3.64 mmol) in dry THF (10.0 mL) was added n-BuLi (2.5M in hexane, 1.7 mL, 4.37 mmol, 1.2 eq.) dropwise at -78 °C under an atmosphere of N2. After addition, the solution was stirred at -78 °C for 30 minutes. Then zinc dichloride (0.993 g, 7.28 mmol, 2 eq.) in dry THF (10.0 mL) was added dropwise at -78 °C under an atmosphere of N2. After addition, the solution was stirred at -78 °C for 30 minutes. Then 3-bromo-6-iodo-8-methyl-imidazo[1,2- a]pyridine (1.23 g, 3.64 mmol, 1 eq.) in toluene (10.0 mL) and tetrakis(triphenylphosphine)palladium(0) (0.421 g, 0.364 mmol, 0.10 eq.) was added dropwise at room temperature under an atmosphere of N2 . The reaction was heated at 100 °C for 12 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution and extracted with dichloromethane. The combined organic layers were washed with water and brine, dried with sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel column chromatography (eluting with MeOH/dichloromethane, 0% to 5%) to give 3-bromo-6-[1-(4-fluoro-3-methoxy-phenyl)imidazol-2-yl]-8-methyl-imidazo[1,2-a]pyridine as a yellow solid. LC/MS (method A) retention time = min; [M+H]+= 403 Step 5: Preparation of methyl N-[5-[6-[1-(4-fluoro-3-methoxy-phenyl)imidazol-2-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 8) A mixture of 3-bromo-6-[1-(4-fluoro-3-methoxy-phenyl)imidazol-2-yl]-8-methyl-imidazo[1,2-a]pyridine (0.3 g, 0.67 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]carbamate ( 0.280 g, 1.00 mmol, 1.50 eq.) was dissolved in acetonitrile (5.37 mL). Sodium carbonate (0.213 g, 2.02 mmol, 3.00 eq.) dissolved in water (2.68 mL) was added. The resulting reaction mixture was purged with nitrogen for 15 mins. Chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'- amino-1,1'-biphenyl)]palladium(II) (0.054 g, 0.067 mmol, 0.10 eq.) was added. The reaction mixture was irradiated with microwave radiation for 1 hour at 100 °C. The reaction mixture was filtered through celite and the filtrate was concentrated. The residue was purified on neutral alumina (eluting in 5-10% methanol/ethyl acetate) to afford an off white solid, which was further washed with tert-butyl methyl ether to afford methyl N-[5-[6-[1-(4-fluoro-3-methoxy-phenyl)imidazol-2-yl]-8-methyl-imidazo[1,2-a]pyridin-3- yl]-2-pyridyl]carbamate as an off white solid. LC/MS (method A) retention time = 0.94 min; [M+H] += 473 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.38 (s, 1H), 8.33 (d, J = 2.2 Hz, 1H), 7.93 (d, J = 8.6 Hz, 1H), 7.86 (s, 1H), 7.72 (s, 1H), 7.55 (dd, J = 8.6, 2.4 Hz, 1H), 7.50 (s, 1H), 7.40 (s, 1H), 7.32 (dd, J = 7.6, 2.4 Hz, 1H), 7.24 (dd, J = 11.0, 8.6 Hz, 1H), 7.20 (s, 1H), 6.88 (dt, J = 8.4, 3.2 Hz, 1H), 3.77 (s, 3H), 3.74 (s, 3H), 2.5 (s, 3H). Example 36: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4- oxadiazin-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (compound 3)
Figure imgf000230_0001
(Compound 3) Step 1: Preparation of 8-methylimidazo[1,2-a]pyridine-6-carbonitrile
Figure imgf000230_0002
To a solution of 6-iodo-8-methyl-imidazo[1,2-a]pyridine (Intermediate I-4, 17.0 g, 59.3 mmol), zinc cyanide (13.9 g, 119 mmol, 2 eq.) and 1,1'-bis(diphenylphosphino)ferrocene (3.29 g, 5.93 mmol, 0.10 eq.) in dimethylformamide (300 mL) was added Pd2(dba)3 (2.71 g, 2.96 mmol, 0.05 eq.) under nitrogen at room temperature. The reaction mixture was stirred at 120 °C for 3 hours under nitrogen. After being cooled to room temperature, the reaction mixture was diluted with water and the mixture was filtered through celite. The filtrate was extracted with ethyl acetate, the combined organic layers were washed with water and brine, dried with sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel column chromatography (eluting with dichloromethane/MeOH, 2% to 5%) to provide 8-methylimidazo[1,2-a]pyridine-6-carbonitrile as a brown solid. LC/MS (method A) retention time = 0.374 min; [M+H] += 158 Step 2: Preparation of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carbonitrile
Figure imgf000231_0001
To a solution of methyl 8-methylimidazo[1,2-a]pyridine-6-carbonitrile (5.00 g, 31.8 mmol) in dimethylformamide (40 mL) was added 1-bromopyrrolidine-2,5-dione (5.95 g, 33.4 mmol, 1.05 eq.) by portions at room temperature. The mixture was stirred at room temperature for 2 hours then diluted with water (200 mL). The precipitate was collected by filtration, washed with water and dried under vacuum to afford 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carbonitrile as a brown solid. LC/MS (method A) retention time = 1.084 min; [M+H] += 238 Step 3: Preparation of ethyl 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboximidate (Intermediate I- 5)
Figure imgf000231_0002
(Intermediate I-5) To a solution of 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carbonitrile (2.00 g, 8.47 mmol) in ethanol/dichloromethane (1:2, 50.0 mL) was added ethanethiolate (0.356 g, 4.24 mmol, 0.50 eq.). The mixture was stirred at 25 °C for 10 hours. Then the reaction mixture was concentrated and purified by silica gel column (dichloromethane/MeOH) to afford ethyl 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6- carboximidate an off-white solid. LCMS (method A) retention time = 0.818; [M+H] += 284.0 Step 4: Preparation of 2-chloro-N-(4-fluoro-3-methoxy-phenyl)acetamide
Figure imgf000231_0003
To a suspension of 4-fluoro-3-methoxy-aniline (10.0 g, 70.9 mmol) and potassium carbonate (10.8 g, 77.9 mmol, 1.10 eq.) in dimethylformamide (50.0 mL) at 0 °C was added, dropwise, a solution of 2- chloroacetyl chloride (8.80 g, 77.9 mmol, 1.00 eq.) in dimethylformamide (5.00 mL). The reaction mixture was stirred at room temperature for 3 hours, then it was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silical gel (petroleum ether/ethyl acetate) to afford 2-chloro-N-(4-fluoro-3-methoxy- phenyl)acetamide as a colorless oil. LC/MS (method B) retention time = 1.03 min; [M+H]+= 218.1 Step 5: Preparation of N-(2-chloroethyl)-4-fluoro-3-methoxy-aniline
Figure imgf000232_0001
To a solution of 2-chloro-N-(4-fluoro-3-methoxy-phenyl)acetamide (10.0 g, 46.0 mmol) in THF (120 mL) at 0 °C was added, dropwise, BH3-THF (1.00 mol/L, 68.9 mL, 68.9 mmol, 1.50 eq.). The reaction mixture was warmed to room temperature and stirred for an additional 3 hours, after which it was poured into ice water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford N-(2-chloroethyl)-4- fluoro-3-methoxy-aniline as a colorless liquid. LC/MS (method B) retention time = 1.23 min; [M+H]+= 204.2 Step 6: Preparation of N-[2-(benzhydrylideneamino)oxyethyl]-4-fluoro-3-methoxy-aniline
Figure imgf000232_0002
To a stirred suspension of diphenylmethanone oxime (CAS 574-66-3, 8.14 g, 41.2 mmol, 1.20 eq.) in DMSO (40.0 mL) at room temperature was added potassium hydroxide (9.64 g, 172 mmol, 5.00 eq.). The reaction mixture was stirred for 3 minutes, then a solution of N-(2-chloroethyl)-4-fluoro-3-methoxy- aniline (7.00 g, 34.4 mmol, 1.00 eq.) in DMSO (10.0 mL) was added dropwise. The reaction mixture was stirred at room temperature for 2 hours, then it was poured into ice water. The aqueous layer was extracted with dichloromethane, the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford N-[2- (benzhydrylideneamino)oxyethyl]-4-fluoro-3-methoxy-aniline as a viscous oil. LC/MS (method B) retention time = 1.63 min; [M+H]+= 365.2 Step 7: Preparation of O-[2-(4-fluoro-3-methoxy-anilino)ethyl]hydroxylamine
Figure imgf000232_0003
A solution of N-[2-(benzhydrylideneamino)oxyethyl]-4-fluoro-3-methoxy-aniline (5.20 g, 15.6 mmol) in 6 M HCl (25.9 mL, 156 mmol) and dioxane (10.0 mL) was refluxed under nitrogen for 8 hours. The resulting mixture was extracted with dichloromethane. The aqueous solution was then adjusted to pH 9 with solid NaHCO3 and extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel (petroleum ether/ethyl acetate) to afford O- [2-(4-fluoro-3-methoxy-anilino)ethyl]hydroxylamine as a light yellow liquid. LC/MS (method B) retention time = 0.66 min; [M+H]+= 201.1 Step 8: Preparation of 3-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-4-(4-fluoro-3-methoxy-phenyl)- 5,6-dihydro-1,2,4-oxadiazine
Figure imgf000233_0001
To a solution of ethyl 3-bromo-8-methyl-imidazo[1,2-a] pyridine-6-carboximidate (Intermediate I-5, 0.100 g, 0.354 mmol) in acetic acid (2.00 mL) was added O-[2-(4-fluoro-3-methoxy-anilino) ethyl] hydroxylamine (0.0710 g, 0.354 mmol, 1.0 eq.). The mixture was stirred at 90 °C for 16 hours. The reaction mixture was quenched with water and concentrated under reduced pressure. The residue was extracted with dichloromethane/MeOH (10:1). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated by reduced pressure. The residue was purified over silica gel (dichloromethane/methanol) to afford 3-(3-bromo-8-methyl-imidazo[1,2-a]pyridin- 6-yl)-4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4-oxadiazine as a brown solid. LC/MS (method A) retention time =1.491 min; [M+H] += 421 Step 9: Preparation of methyl N-[5-[6-[4-(4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]- 8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 3) To a mixture of 3-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-4-(4-fluoro-3-methoxy-phenyl)-5,6- dihydro-1,2,4-oxadiazine (0.0200 g, 0.0477 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-2-pyridyl]carbamate (0.0172 g, 0.0620 mmol, 1.30 eq.) in dioxane/H2O (4:1) was added BrettPhosPdG3 (0.00432 g, 0.00477 mmol, 0.100 eq.) and K2CO3 (0.0198 g, 0.143 mmol, 3.00 eq.). The mixture was stirred at 45 °C for 2 hours under N2 atmosphere, then it was concentrated under reduced pressure and the residue was diluted with brine (10.0 mL) and extracted with dichloromethane/MeOH (10:1). The combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting with dichloromethane/MeOH) then further purified by trituration with acetonitrile to afford methyl N-[5-[6-[4- (4-fluoro-3-methoxy-phenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]-8-methyl-imidazo[1,2-a]pyridin-3-yl]-2- pyridyl]carbamate as a white powder. LC/MS (method A) retention time =1.460 min; [M+H] + = 491 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.44 (s, 1H), 8.37 (d, J = 2.2 Hz, 1H), 8.22 (s, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.73 (s, 1H), 7.70 (dd, J = 8.6, 2.4 Hz, 1H), 7.11 - 7.00 (m, 3H), 6.63 - 6.57 (m, 1H), 4.14 (t, J = 4.4 Hz, 2H), 3.84 - 3.78 (m, 2H), 3.73 (s, 3H), 3.72 (s, 3H), 2.42 (s, 3H). Example 37: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]- 8-methyl-imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 1)
Figure imgf000234_0001
(Compound 1) Step 1: Preparation of N-(2-chloroethyl)-4-fluoro-aniline
Figure imgf000234_0002
To a solution of 4-fluoroaniline (2.00 g, 18.0 mmol) in a mixture of methanol (30 mL) and acetic acid (1.03 mL, 18.0 mmol, 1.00 eq.) at room temperature was added portionwise sodium cyanoborohydride (1.79 g, 27.0 mmol, 1.50 eq.) followed by 2-chloroacetaldehyde (2.59 mL, 21.6 mmol, 1.20 eq.). The reaction mixture was stirred at room temperature for 12 hours. The reaction was quenched with ice water and then extracted using ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by flash chromatography over neutral alumina (eluting cyclohexane/ethyl acetate, 9:1) to afford N-(2-chloroethyl)-4-fluoro-aniline as a brown oil. LC/MS (method B) retention time = 1.11 min; [M+H]+= 174.1 Step 2: Preparation of N-[2-(benzhydrylideneamino)oxyethyl]-4-fluoro-aniline
Figure imgf000234_0003
To a stirred suspension of diphenylmethanone oxime (CAS 574-66-3, 0.855 g, 4.33 mmol) in DMSO (13.0 mL) at room temperature was added sodium hydroxide (0.347 g, 8.67 mmol, 2.00 eq.). Then a solution of N-(2-chloroethyl)-4-fluoro-aniline (0.828 g, 4.77 mmol, 1.10 eq.) in DMSO (2.0 mL) was added dropwise. The reaction mixture was stirred at room temperature for 12 hours, then it was poured into ice water. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on neutral alumina (cyclohexane/ethyl acetate) to afford N-[2-(benzhydrylideneamino)oxyethyl]-4-fluoro-aniline. 1H NMR (400 MHz, CDCl3, ppm) δ = 7.43 - 7.52 (m, 5 H), 7.31 - 7.42 (m, 5 H), 6.89 (br t, J = 8.76 Hz, 2 H), 6.51 - 6.57 (m, 2 H), 4.36 - 4.43 (m, 2 H), 3.39 - 3.44 (m, 2 H).
Figure imgf000235_0001
N-[2-(benzhydrylideneamino)oxyethyl]-4-fluoro-aniline (3.80 g, 11.4 mmol) in 6 M HCl (80.0 mL) was refluxed under nitrogen for 12 hours. Saturated aqueous NaHCO3 was added. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to afford O-[2-(4- fluoroanilino)ethyl]hydroxylamine as a viscous oil. LC/MS (method A) retention time = 1.07 min; [M+H]+= 171.2 Step 4: Preparation of 3-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-4-(4-fluorophenyl)-5,6-dihydro- 1,2,4-oxadiazine
Figure imgf000235_0002
O-[2-(4-fluoroanilino)ethyl]hydroxylamine (0.633 g, 3.72 mmol, 1.05 eq.) was added to solution of ethyl 3-bromo-8-methyl-imidazo[1,2-a]pyridine-6-carboximidate (Intermediate I-5, 1.00 g, 3.54 mmol) in acetic acid (20.0 mL). The solution was stirred at room temperature for 4 hours, then at 95 °C for 5 hours. The reaction mixture was cooled down to room temperature, and water was added. The mixture was concentrated under reduced pressure. The residue was taken up in dichloromethane, then washed with brine, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography over silica gel (eluting dichloromethane/MeOH) to afford 3-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6- yl)-4-(4-fluorophenyl)-5,6-dihydro-1,2,4-oxadiazine as a brown solid. LC/MS (method A) retention time = 1.13 min; [M+H]+= 389.1 Step 5: Preparation of methyl N-[5-[6-[4-(4-fluorophenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate To a mixture of 3-(3-bromo-8-methyl-imidazo[1,2-a]pyridin-6-yl)-4-(4-fluorophenyl)-5,6-dihydro-1,2,4- oxadiazine (0.500 g, 1.28 mmol) and methyl N-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2- pyridyl]carbamate (0.536 g, 1.93 mmol, 1.50 eq.) in dioxane/H2O (5:1, 18.00 mL) was added Pd(dppf)Cl2 (0.094 g, 0.128 mmol, 0.100 eq.) and potassium carbonate (0.444 g, 3.21 mmol, 3.00 eq.). The mixture was stirred at 45 °C for 1 hour under N2 atmosphere. Water was added to the reaction mixture which was concentrated under reduced pressure. The residue was extracted with dichloromethane/MeOH (10:1). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under. Purification over silica gel (dichloromethane/methanol) followed by trituration with acetonitrile afforded methyl N-[5-[6-[4-(4-fluorophenyl)-5,6-dihydro-1,2,4-oxadiazin-3-yl]-8-methyl- imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as a grey solid. LC/MS (method A) retention time = 0.92 min; [M+H]+ = 461.2 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.46 (s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 8.22 (d, J = 1.5 Hz, 1 H), 8.00 (d, J = 8.7 Hz, 1 H), 7.75 (d, J = 8.7 Hz, 2 H), 7.25 - 7.15 (m, 2 H), 7.10 (d, J = 8.7 Hz, 2 H), 7.01 (s, 1 H), 4.14 (t, J = 4.4 Hz, 2 H), 3.80 (d, J = 4.4 Hz, 2 H), 3.73 (s, 3 H), 2.39 (s, 3 H). Example 38: Preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1- yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 9)
Figure imgf000236_0001
(Compound 9) Step 1: Preparation of 2-chloro-5-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]pyridine
Figure imgf000236_0002
A solution of 4-fluoro-3-methoxy-benzamide (1.60 g, 9.46 mmol) in 1,1-dimethoxy-N,N-dimethyl- methanamine (8.00 mL) was heated at 100 °C for 2 hours. The mixture was concentrated under reduced pressure. The residue was taken up in acetic acid (16.0 mL), and (6-chloro-3-pyridyl)hydrazine (1.36 g, 9.46 mmol, 1.00 eq.) was added. Then the mixture was heated at 95 °C for 3 hours. The reaction mixture was then concentrated under vacuum. The mixture was adjusted to pH 7 with saturated aqueous NaHCO3 solution. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by silica gel column chromatography (eluting with Ethyl acetate /petroleum ether) to give 2-chloro-5-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]pyridine as an orange solid. LC/MS (method A) retention time = 1.175 min; [M+H] += 305 Step 2: Preparation of N-(2,2-dimethoxyethyl)-5-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1- yl]pyridin-2-amine
Figure imgf000237_0001
To a solution of 2-chloro-5-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]pyridine (0.350 g, 1.15 mmol) in toluene (15.0 mL) was added 2,2-dimethoxyethanamine (0.133 g, 1.26 mmol, 1.10 eq.), sodium tert-butoxide (0.276 g, 2.87 mmol, 2.50 eq.), Pd2(dba)3 (0.0526 g, 0.0574 mmol, 0.05 eq.) and BINAP (0.0358 g, 0.0574 mmol, 0.05 eq.) under nitrogen. The mixture was heated at 80 °C for 3 hours. The reaction mixture was then cooled down to room temperature, then water was added. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by reverse phase chromatography on a C18 column (eluting with Acetonitrile/H2O containing 0.1% NH3/H2O) to provide N-(2,2-dimethoxyethyl)-5-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]pyridin- 2-amine as a yellow oil. LC/MS (method A) retention time = 1.13 min; [M+H] += 374.2 Step 3: Preparation of 6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridine
Figure imgf000237_0002
A solution of N-(2,2-dimethoxyethyl)-5-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]pyridin-2-amine (0.0200 g, 0.0429 mmol) in Eaton's reagent (CAS 39394-84-8, 0.600 mL, 3.78 mmol, 9.0 eq.) was heated at 50 °C for 1 hour. Saturated aqueous NaHCO3 solution was added to the reaction mixture. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with water and brine, dried with sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting with MeOH/dichloromethane) to give 6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridine as a yellow oil. LC/MS (method A) retention time = 0.70 min; [M+H] += 310.2 Step 4: Preparation of 6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]-3-iodo-imidazo[1,2-a]pyridine
Figure imgf000238_0001
To a solution of 6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridine (45.0 mg, 0.145 mmol) in acetonitrile (1.20 mL) was added 1-iodopyrrolidine-2,5-dione (0.0327 g, 0.145 mmol, 1.0 eq.). The mixture was stirred at room temperature for 2 hours. Then the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel column chromatography (eluting with MeOH/dichloromethane) to give 6-[5-(4-fluoro-3-methoxy-phenyl)- 1,2,4-triazol-1-yl]-3-iodo-imidazo[1,2-a]pyridine as a yellow oil. LC/MS (method A) retention time = 1.08 min; [M+H] += 436.1 Step 5: Preparation of methyl N-[5-[6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]imidazo[1,2- a]pyridin-3-yl]-2-pyridyl]carbamate (Compound 9) To a solution of 6-[5-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-1-yl]-3-iodo-imidazo[1,2-a]pyridine (90.0 mg, 0.207 mmol) in dioxane/H2O (4:1, 1.50 mL) was added methyl N-[5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-2-pyridyl]carbamate (0.115 g, 0.414 mmol, 2.0 eq.), [1,1'-1,1'- bis(diphenylphosphino)ferrocene-palladium(II) (0.0151 g, 0.0207 mmol, 0.05 eq.) and potassium carbonate (0.0715 g, 0.517 mmol, 2.5 eq.) under nitrogen. The mixture was heated at 70 °C for 3 hours. Then the reaction mixture was diluted with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel column chromatography (eluting with MeOH/dichloromethane) and further triturated with acetonitrile to afford methyl N-[5-[6-[5-(4-fluoro-3- methoxy-phenyl)-1,2,4-triazol-1-yl]imidazo[1,2-a]pyridin-3-yl]-2-pyridyl]carbamate as an off-white solid LC/MS (method A) retention time = 0.95 min; [M+H] += 460.1 1H NMR (400 MHz, DMSO-d6, ppm) δ = 10.44 (s, 1 H), 8.89 - 8.77 (m, 1 H), 8.47 (d, J = 1.6 Hz, 1 H), 8.29 (s, 1 H), 7.98 - 7.87 (m, 3 H), 7.78 (d, J = 9.4 Hz, 1 H), 7.42 (dd, J = 8.3, 2.0 Hz, 1 H), 7.34 (dd, J = 9.5, 1.8 Hz, 1 H), 7.26 (dd, J = 11.4, 8.4 Hz, 1 H), 7.05 (ddd, J = 8.4, 4.2, 2.0 Hz, 1 H), 3.72 (s, 3 H), 3.71 (s, 3 H). Example 39: Preparation of 5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2- a]pyridin-3-yl]pyridin-2-amine
Figure imgf000239_0001
A solution of sodium carbonate (12.9 mg, 0.122 mmol, 3.05 eq.) in water (0.200 mL) was added to 2- aminopyridine-5-boronic acid pinacol ester (14.1 mg, 0.0638 mmol, 1.60 eq.), followed by addition of a solution of 3-bromo-6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine (Intermediate I-1, 15.5 mg, 0.0400 mmol) in acetonitrile (0.200 mL). The mixture was flushed with nitrogen. A solution of chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino- 1,1′-biphenyl)]palladium(II) (3.3 mg, 0.0042 mmol, 0.1 eq.) in acetonitrile (0.200 mL) was added. The vial was flushed again with nitrogen, then heated at 100 °C for 16 hours. The mixture was then cooled down to room temperature and the solvent was removed under reduced pressure. A mixture of dimethylacetamide and methanol was added to the crude residue, and the resulting solution was filtered over a filter plate containing silica gel. The solvent was removed under reduced pressure. The residue was purified by reverse phase HPLC to afford 5-[6-[2-(4-fluoro-3-methoxy-phenyl)-1,2,4-triazol-3- yl]imidazo[1,2-a]pyridin-3-yl]pyridin-2-amine LC/MS (method C) retention time = 0.54 min; [M+H] += 402.2 Biological examples: The fungicidal activity of the compounds of the invention have been tested as follows: Phytophthora infestans / tomato / leaf disc preventative (late blight) Tomato leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are incubated at 16 °C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application). The following compounds gave at least 80% control of Phytophthora infestans at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 77, 80, 81, 85, 86, 87, 90, 92, 95, 101, 104, 107, 108, 111, 112. Plasmopara viticola / grape / leaf disc preventative (late blight) Grape vine leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are incubated at 19 °C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 - 8 days after application). The following compounds gave at least 80% control of Plasmopara viticola at 200 ppm when compared to untreated control under the same conditions, which showed extensive disease development: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14, 16, 17, 18, 19, 20, 24, 25, 26, 27, 28, 32, 33, 36, 37, 38, 41, 43, 44, 46, 49, 75, 77, 80, 86, 87, 112. Pythium ultimum / liquid culture (seedling damping off) Mycelia fragments and oospores of a newly grown liquid culture of the fungus are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal mycelia/spore mixture is added. The test plates are incubated at 24 °C and the inhibition of growth is determined photometrically 2-3 days after application. The following compounds gave at least 80% control of Pythium ultimum at 20 ppm when compared to untreated control under the same conditions, which showed extensive disease development: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 48, 49, 50, 51, 53, 54, 55, 56, 57, 61, 65, 68, 69, 70, 71, 75, 76, 77, 79, 80, 85, 86, 87, 90, 92, 95, 104, 107, 109, 112, 113.

Claims

Claims 1. A compound of formula (I) 2b
Figure imgf000241_0001
a 5-8-membered heterocycle, a 6-12-membered aromatic ring or a 5-11-membered heteroaromatic ring, wherein each of the 5-8-membered carbocycle, the 5-8-membered heterocycle, the 6-12-membered aromatic ring or the 5-11-membered heteroaromatic ring is optionally substituted with one to four substituents independently selected from R1; A is CH or N; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than four A3 are N, preferably no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, hydroxy, amino, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1- 6alkylaminocarbonyl and diC1-6alkylaminocarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; and wherein optionally two geminal R1 taken together with the carbon they are attached to form a carbonyl group; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, C1-6alkylcarbonyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1- 6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, and C1-6alkylcarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; and R6 is selected from C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1- 6alkylamino, diC1-6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino, wherein each of the C1- 6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1-6alkylamino, diC1- 6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino groups is optionally substituted with one to three substituents independently selected from halogen and CN; or a salt or N-oxide thereof. 2. The compound according to claim 1, wherein four A3 are CR4 and one A3 is N. 3. The compound according to claim 1 or 2, wherein , and preferably the four A3 are CR4.
Figure imgf000242_0001
4. The compound according to claim 1 or 2, wherein 3 , and preferably the four A3 are CR4.
Figure imgf000242_0002
5. The compound according to claim 1, wherein the five A3 are CR4. 6. The compound according to any one of the preceding claims, wherein A1 is a carbon atom and A2 is a nitrogen atom. 7. The compound according to any one of the claims 1 to 5, wherein A1 is a carbon atom and A2 is a carbon atom. 8. The compound according to any one of the claims 1 to 5, wherein A1 is a nitrogen atom and A2 is a carbon atom. 9. The compound according to any one of the claims 1 to 5, wherein A1 is a nitrogen atom and A2 is a nitrogen atom. 10. The compound according to any one of the claims 1 to 5, wherein ring W * , ,
Figure imgf000243_0001
wherein * represents the point of attachment to the imidazopyridine group in formula (I), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2-6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1- 4alkyl, C2-6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN. 11. The compound according to claim 10, wherein ring W * selected from:
Figure imgf000243_0002
wherein * represents the point of attachment to the imidazopyridine group in formula (I), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2-6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN. 12. The compound according to any one of the preceding claims, wherein ring W is a 5-8-membered heterocycle or a 5-11-membered heteroaromatic ring, wherein each of the 5-8-membered heterocycle or the 5-11-membered heteroaromatic ring is optionally substituted with one to four substituents independently selected from R1 A is N; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than three A3 are N; R1 is selected from halogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C1- 6alkoxy, and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl- C1-4alkyl, C1-6alkoxy, groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; R2a, R2b and R2c independently selected from hydrogen, halogen, CN, C1-6alkyl, C3-6cycloalkyl, C1- 6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkoxy, and -NHC(O)C1-6alkyl; R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2- 6alkynyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-6alkyl, groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; and R6 is selected from C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl and C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, wherein each of the C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl and C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl groups is optionally substituted with one to three substituents independently selected from halogen and CN. 13. A composition comprising a fungicidally effective amount of a compound as defined in any one of claims 1 to 12. 14. A composition according to claim 13, wherein the composition further comprises at least one compound selected among an additional active ingredient, an appropriate formulation inert, a carrier, an adjuvant, and any mixtures thereof. 15. A method of combating, preventing or controlling phytopathogenic diseases which comprises applying to a phytopathogen, to the locus of a phytopathogen, to a plant susceptible to attack by a phytopathogen, or to a plant propagation material thereof, a fungicidally effective amount of a compound according to any one of claims 1 to 12, or a composition comprising a compound according to any one of claims 1 to 12, or a composition according to claim 13 or 14. 16. A compound of formula (II)
Figure imgf000245_0001
; wherein * represents the point of attachment to the imidazopyridine group in formula (II), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2- 6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than four A3 are N, preferably no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, hydroxy, amino, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1- 6alkylaminocarbonyl and diC1-6alkylaminocarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; and wherein optionally two geminal R1 taken together with the carbon they are attached to form a carbonyl group; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, C1-6alkylcarbonyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1- 6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, and C1-6alkylcarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; and X is Cl, Br or I; or a compound of formula (XV) ; wherein * represents the point of attachment to the imidazopyridine group in formula (XV), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2- 6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than four A3 are N, preferably no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, hydroxy, amino, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1- 6alkylaminocarbonyl and diC1-6alkylaminocarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; and wherein optionally two geminal R1 taken together with the carbon they are attached to form a carbonyl group; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, C1-6alkylcarbonyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1- 6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, and C1-6alkylcarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN; or a compound of formula (XXVI)
Figure imgf000248_0001
* wherein selected from:
Figure imgf000248_0002
; wherein * represents the point of attachment to the imidazopyridine group in formula (XXVI), and # represents the point of attachment to the ring formed by the A3 groups, and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl and C2- 6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A is CH or N; A1 is a carbon or nitrogen atom; A2 is a carbon or nitrogen atom; A3 are independently CR4 or N, with the proviso that no more than four A3 are N, preferably no more than three A3 are N, preferably no more than two A3 are N, preferably no more than one A3 is N, and more preferably the five A3 are CR4; R1 is selected from halogen, hydroxy, amino, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3- 6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl and CN, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1- 6alkylaminocarbonyl and diC1-6alkylaminocarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; and wherein optionally two geminal R1 taken together with the carbon they are attached to form a carbonyl group; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and R4 are independently selected from hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1- 6alkoxy, halogen, CN, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, C1-6alkylcarbonyl, and hydroxy, wherein each of the C1-6alkyl, C1-6alkoxy, C1- 6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkoxy, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkylsulfanyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl C1-6alkoxycarbonyl, C1-6alkylaminocarbonyl, diC1- 6alkylaminocarbonyl, and C1-6alkylcarbonyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy, and CN. 17. A compound of formula (XXII) ,
Figure imgf000250_0001
; wherein * represents the point of attachment to the imidazopyridine group in formula (XXII) and wherein R11 is selected from hydrogen, C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, C2- 6alkenyl and C2-6alkynyl, wherein each of the C1-6alkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl- C1-4alkyl, C2-6alkenyl, and C2-6alkynyl groups is optionally substituted with one to three substituents independently selected from halogen, hydroxy and CN; A1 is a carbon or nitrogen atom; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; and X is Cl, Br or I. 18. A compound of formula (XVII) wherein A is CH or N; R2a, R2b and R2c are independently selected from hydrogen, hydroxy, halogen, CN, C1-6alkyl, C3- 6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1-4alkyl, C1-6alkylsulfanyl. C1-6alkylsulfinyl, C1- 6alkylsulfonyl, C1-6alkoxy, amino, and -NHC(O)C1-6alkyl; and preferably R2a, R2b and R2c are independently selected from hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkoxy-C1-6alkyl, C3-6cycloalkyl-C1- 4alkyl, and C1-6alkoxy; R6 is selected from C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1- 6alkylamino, diC1-6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino, wherein each of the C1- 6alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, C1-6alkoxyC1-6alkyl, C1-6alkylamino, diC1- 6alkylamino, C1-6alkoxyamino, and C1-6alkylC1-6alkoxyamino groups is optionally substituted with one to three substituents independently selected from halogen and CN; and X is Cl, Br or I.
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