NZ765780B2 - 2-(morpholin-4-yl)-1,7-naphthyridines - Google Patents
2-(morpholin-4-yl)-1,7-naphthyridines Download PDFInfo
- Publication number
- NZ765780B2 NZ765780B2 NZ765780A NZ76578015A NZ765780B2 NZ 765780 B2 NZ765780 B2 NZ 765780B2 NZ 765780 A NZ765780 A NZ 765780A NZ 76578015 A NZ76578015 A NZ 76578015A NZ 765780 B2 NZ765780 B2 NZ 765780B2
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- New Zealand
- Prior art keywords
- general formula
- intermediate compound
- phenyl
- alkyl
- ghmatters
- Prior art date
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- YJCWMEVTGIOUNH-UHFFFAOYSA-N C1CN(CCO1)C1=CC=C2C=CN=CC2=N1 Chemical class C1CN(CCO1)C1=CC=C2C=CN=CC2=N1 YJCWMEVTGIOUNH-UHFFFAOYSA-N 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract 24
- 238000000034 method Methods 0.000 claims abstract 7
- 238000002360 preparation method Methods 0.000 claims abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 8
- 229910052739 hydrogen Inorganic materials 0.000 claims 7
- 239000001257 hydrogen Substances 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 6
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims 4
- 239000003960 organic solvent Substances 0.000 claims 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- 150000002367 halogens Chemical group 0.000 claims 3
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical group 0.000 claims 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims 2
- 229910052740 iodine Inorganic materials 0.000 claims 2
- 125000002346 iodo group Chemical group I* 0.000 claims 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical group [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims 2
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 claims 2
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims 2
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 claims 1
- 238000009835 boiling Methods 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Abstract
The present invention relates to the preparation of substituted 2-(morpholin-4-yl)-1,7-naphthyridine compounds of general formula (Ib), to intermediate compounds useful for preparing said compounds and methods for preparing said intermediate compounds.
Claims (18)
1. Use of an intermediate compound in the preparation of a compound of general formula (Ib): in which: R represents wherein * indicates the point of attachment of said group with the rest of the molecule; 2 7 8 R represents hydrogen, halogen, -NR R , CN, C -C -alkyl, C -C -alkoxy, 3- to 10-membered 1 6 1 4 heterocycloalkoxy, C -C -alkenyl, C -C -cycloalkyl, 3- to 10-membered heterocycloalkyl, 4- to 2 4 3 6 10-membered heterocycloalkenyl, phenyl, heteroaryl, 7 8 9 9 9 9 10 7 7 10 -(CO)NR R , -(SO )R , -(SO)R , -SR , -N=(SO)R R , –(PO)(OR ) , –(PO)(OR )R , –(PO)(R ) , wherein each C -C -alkyl, C -C -alkoxy, C -C -cycloalkyl, 3- to 10-membered 1 6 1 4 3 6 heterocycloalkyl, phenyl or heteroaryl is optionally substituted, one or more times, independently from each other, with halogen, OH, amino, -NR R , C -C -alkyl optionally substituted with hydroxyl or phenyl, C -C -haloalkyl, C -C -alkoxy, C -C -cycloalkyl, 3- to 6-membered heterocycloalkyl, 1 2 1 3 3 6 7 7 8 7 10 8 7 phenyl, -(CO)OR , -(CO)NR R , -NR (CO)R , -NR (CO)OR , 9 9 7 9 11 10 7 7 10 -(SO2)R , -SR , -NR (SO2)R , -((SO)=NR )R , -(PO)(OR )2, –(PO)(OR )R , or with a heteroaryl group; 20147888_1 (GHMatters) P105077.NZ.1 wherein each 4- to 10-membered heterocycloalkenyl is optionally substituted, one or more times, independently from each other, with methyl; R represents hydrogen or methyl; R , R represent, independently from each other, hydrogen, C -C -alkyl, C -C -cycloalkyl or 1 6 3 6 phenyl, which phenyl is optionally substituted, one or more times, with halogen; R represents C -C -alkyl or phenyl, wherein each C -C -alkyl or phenyl is optionally substituted, 1 4 1 4 one or more times, independently from each other, with R ; R represents C -C -alkyl; or 9 10 9 10 R and R together, in case of -N=(SO)R R group, represent a 5- to 8-membered heterocycloalkyl group; 11 7 7 8 R represents hydrogen, C -C -alkyl, -(CO)OR , -(CO)NR R or CN; R represents halogen, OH or C -C -alkoxy, wherein the intermediate compound is selected from the group consisting of: , , , 20147888_1 (GHMatters) P105077.NZ.1 , , and in which R and R are as defined for the compound of general formula (Ib); R represents hydrogen; X represents chloro, bromo or iodo; and Y represents OH, -O-SO -CF , Cl, Br, I, SH or –SO Cl. 2 3 2
2. Method to prepare an intermediate compound of general formula 5 20147888_1 (GHMatters) P105077.NZ.1 characterized in that the compound of general formula 4, in which R represents hydrogen and R represents hydrogen or methyl, is reacted in an organic solvent at a temperature between -20°C and the boiling point of the solvent using a strong base to obtain the compound of general formula 5.
3. Method according to claim 2, wherein the temperature is between -5°C and 30°C.
4. Method according to claim 2 or 3, in which the strong base is lithium bis(trimethylsilyl)amide (LiHMDS), potassium bis(trimethylsilyl)amide (KHMDS), sodium bis(trimethylsilyl)amide (NaHMDS) or lithium diisopropylamide (LDA).
5. Method according to any one of claims 2 to 4, in which the organic solvent is an aprotic organic solvent.
6. Method according to claim 5, in which the organic solvent is tetrahydrofuran or N,N- dimethylformamide.
7. Intermediate compound of general formula 5 in which R represents H and R represents methyl.
8. Intermediate compound of general formula 4 20332040_1 (GHMatters) P105077.NZ.1 in which R represents H and R represents methyl.
9. Intermediate compound of general formula 11 1 3 4 in which R , R and R are as defined in claim 1 for the intermediate compound of general formula 11.
10. Intermediate compound of general formula 12 1 3 4 in which R , R and R are as defined in claim 1 for the intermediate compound of general formula 12 and in which X represents chloro, bromo or iodo. 20147888_1 (GHMatters) P105077.NZ.1
11. Intermediate compound of general formula 39 in which Y represents OH, -O-SO -CF , Cl, Br, I, SH or –SO Cl. 2 3 2
12. Intermediate compound of general formula 39 according to claim 11, in which Y represents OH, -O-SO2-CF3 or Cl.
13. Intermediate compound of general formula 9 in which R represents H and R represents methyl.
14. Intermediate compound of general formula 15 1 3 4 in which R , R and R are as defined in claim 1 for the intermediate compound of general formula 15. 20147888_1 (GHMatters) P105077.NZ.1
15. Intermediate compound of general formula 16 1 3 4 in which R , R and R are as defined in claim 1 for the intermediate compound of general formula 16.
16. Use according to claim 1, substantially as herein described with reference to any one of the Examples.
17. Method according to claim 2, substantially as herein described with reference to any one of the Examples.
18. Intermediate compound according to any one of claims 7 to 15, substantially as herein described with reference to any one of the Examples. 20147888_1 (GHMatters) P105077.NZ.1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14179692 | 2014-08-04 | ||
| EP15159342 | 2015-03-17 | ||
| NZ728416A NZ728416B2 (en) | 2014-08-04 | 2015-08-03 | 2-(morpholin-4-yl)-1,7-naphthyridines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ765780A NZ765780A (en) | 2023-11-24 |
| NZ765780B2 true NZ765780B2 (en) | 2024-02-27 |
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