AU602226B2 - New preparation process - Google Patents
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- AU602226B2 AU602226B2 AU19024/88A AU1902488A AU602226B2 AU 602226 B2 AU602226 B2 AU 602226B2 AU 19024/88 A AU19024/88 A AU 19024/88A AU 1902488 A AU1902488 A AU 1902488A AU 602226 B2 AU602226 B2 AU 602226B2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
I I f ._i 602226
AUSTRALIA
PATENTS ACT 1952 COMPLETE SPECIFICATION
(ORIGINAL)
FOR OFFICE USE Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority: Related Art: Thi docurnnt contains the amrendments made undthr Section +9 and is corrcct for pJn.ting
I
It It
'C
i .7e N) I N) on),) N, C) N) CC
*C
n) C zcCCN 3'CC n) C
'CC
TO BE COMPLETED BY APPLICANT 'C cc I C NC N) n 4.
Nc N) Name of Applicant: Address of Applicant: Actual Inventors: Address for Service: BAYER AKTIENGESELLSCHAFT D-5090 Leverkusen, Bayerwerk, Germany Dr. Rudolf Zerbes Dr. Michael Preiss ARTHUR S. CAVE CO.
Patent Trade Mark Attorneys Level Barrack Street SYDNEY N.S.W. 2000
AUSTRALIA
Complete Specification for the invention entitled NEW PREPARATION PROCESS.
The following statement is a full description of this invention including the best method of performing it known to me:- 1 ASC 49
L,
I I I t The invention relates to a new process for the preparation of 4-oxo-3-quinoLine-carboxyLic acids which are used as intermediates for the preparation of known quinoLonecarboxylic acids having pharmaceutical activity.
it is known that 1-cycLopropyL-7-chLoro-6-fLuoro- 1,4-dihydro-4-oxo-3-quinoLine-carboxyLic acids are obtained in the following way: 1st stage: 4 t 1' CFa C CC
I
CH-COOR
11
CH-N(CH
3 2 (2) 0 F C COOR CYINCl CH-N(CH 3 (3) 2nd stage: t CC (3 (4) 0 C COOR
-(CH
3 2 NH C, a l CH-NEFKI 3rd stage:
+K
2 C0 3
I
Le A 25 272 1A 4th stage: hydroLys is (6) It has also beei following way: 1st stage: CF0 +CC CH 2 2nd stage: decarboxyL a 3rd stage: CH(QEt) 3
COOH
Cl' (7) disclosed to prepare in the ni C 0 2 R 0 Fl C-CH C0 2 R) 2 C0 2
R
-4 t io n 0 c laI 0 2 R a c SCH-0C 2
H-
4th stage: f>-NH 2 Le A 25 272 0 cI l C -r 2stage: 0
SK
2
C
3 0 2
R
Cl 6th stage: 0 hydrolysis
OOH
C 1 However, aLL the known processes have the disadvantage that the target compound is prepared via many intermediate stages.
Moreover, elaborate separation and drying operations must be carried out.
S The washing procedures which become necessary thereby mean that large amounts of solvents must be incinerated or reprocessed.
t i C It is necessary to apply elaborate analytical methods for the characterization of the intermediate stages.
The invention relates to a process for the preparation of quinolonecarboxylic acids of the general formula I
X
4 0 X OOH
X
1 Ri in which R represents propyl, cyclopropyl, isopropyl Le A 25 272 3 1;.u r :a
I
or vinyl, X denotes fluorine, chlorine, Br, CN, NO 2 or hydrogen, and X 3 and X represent fluorine, chlorine, NO 2 or hydrogen, which is characterized in that a compound of the formula OC1
(II)
i;ii 'I;r i q ji I:1
M
3 in which X to X have the abovementioned meaning, and
X
5 represents halogen, in particular chlorine or fluorine, is reacted, without isolation of intermediate stages in a so-called one-pot reaction, with a compound of the formula (III)
'CI
f:
CH-COOR
2
I
CH-NR
3
R
3 (III) in which R and R are identical or different and represent C -C 4 -alkyl, in the presence of a solvent and of a base, where appropriate heating to 50 0 C to 150 0 C, to give the compounds of the formula IV
X
4 0 0
X
3
OR
2
(IV)
tF Le A 25 272 4 these compounds IV are subjected to an amine exchange at temperatures of 500C to 1200C in the presence of the abovementioned solvents and in the presence of an amine of the formula R 1
NH
2 in which R has the abovementioned meaning, resulting in the compounds of the formula x 4 0 0 I II II X -C-C-OR 2 (v) X1 having the abovementioned radical meanings, and subsequently the compounds V are cyclized and hydrolysed at temperatures between 800C and 180 0 C in the presence of a base, and the compounds of the formula I are precipitated by addition of acid.
The compounds which are prepared according to the invention, in particular, are those in which R1 in formula I represents a cyclopropyl radical.
Preferably: X 1 and X hydrogen,
SX
2 chlorine and 3 X fluorine.
Additionally preferred compounds of the formula 1 2 I are those in which R denotes cyclopropyl, X repre- 1 3 4 20 sents chlorine, and X and X denote fluorine, while X represents hydrogen.
Compounds which are furthermore preferred are those in which X represents fluorine, and X and X represent chlorine, while X denotes hydrogen.
Given the complicated course of the reaction, it has to be designated extremely surprising that the compound 1-cyclopropyl-7-chloro-6-fLuoro-1,4-dihydro-4-oxo- 3-quinoline-carboxylic acid can be prepared without isolation of intermediates in a "one-pot." reaction in excellent yields by the following route: Le A 25 272 a) acylation FD 1 CH-COOR 2 uI II Ci ci CH-NR 3
R
3 0 Ii tert. org. BASE
OOR
0 C inert org. soLvent Cl Cl CH-NR 3
R
3 Suitable org. solvents are: toLuene, xyLene, cyclohexane, open-chain hydrocarbons (mixtures), DMF, and
DMSO.
Bases which can be used are: tert. org. amines such as
R
3 N with R C 1
-C
4 -aky, benzyl, cycl. amines R-N
N-P
0 N-R pyridine, etc., with R C 1
-C
4 -aky.
The temperatures for the acylation of the dimethylaminoacrylic ester are between 50 0 C and 150 0 C, preferably at 80 0 C to 120 0
C.
Hydrochloride, which precipitates out during the reaction, of the auxiliary base can be separated out via a filter or be removed by extraction by stirring with water.
The org. phase with the aroylacrylic ester is further reacted with cyclopropyLamine.
Le A 25 272 -6- SThis reaction can be carried out in the same solvent or, after evaporation (in vacuo or under atmospheric pressure), in another solvent.
b) amine exchange: 0 COOR -(CH3 )2NH C -H2 Cl Cl CH-N(CH 3 2 0 C
-COOR
Cl Cl H-NH-< Suitable solvents are: toluene, xylene, cyclohexane, open-chain hydrocarbons (mixtures), alcohols,
SDMF,
DMSO and Sbutylglycol.
S 15 The temperatures for the amine exchange are at 0 C to 120 0 C, preferably at 650C to 850C.
S. The reaction mixture is maintained further at the t elevated temperature until the evolution of gas (dimethylamine) ceases.
If the amine exchange is carried out in a lowboiling diluent such as, for example, cyclohexane, the solvent is evaporated off before the cyclization (in vacuo or under atmospheric pressure) and replaced by a higherboiling diluent such as, for example, butylglycol.
Le A 25 272 7 c) cyclization: 0
II
c ooR C
K
2
CO
3
C
l c l CH-NH-<
O
OOR
Cl Suitable solvents are: higher alcohols such as butylglycol i-propyl alcohol, ethylene glycol butanol, triethylene glycol, polyethylene glycol, amino alcohols such as diethylaminoethanol,
DMF,
DMSO,
dioxane and N-methylpyrrolidone.
The cyclization to give the quinolone system is carried out at temperatures between 80 0 C and 1800C, preferably at 130 0 C to 160 0 C, in the presence of a base.
Bases which can be used are: Na tert.-butylate, NaH and
K
2 C0 3 20 The base is used in an equimolar amount or up to an excess of 3 moLe-equivalents, preferably in an excess of 0.1 to 0.5 mole-equivalents.
Le A 25 272 -8d) hydrolysis and precipitation 0 0 i2 CO2R
OOH
I I I For the hydrolysis, the reaction mixture is cooled Sto about 100 0 and water is added.
Owing to the excess of base in the cyclization, the hydrolysis is complete within a short time at temperatures of 500C to 1000C.
The quinolone carboxylic acid is precipitated by addition of a mineral acid or an org. acid and is isolated.
Suitable and preferred acids are: sulphuric acid, hydrochloric acid and i acetic acid.
Example 1 28.8 g of ethyL N,N-dimethylamino-acrylate and I 26 g of N,N-dimethylbenzylamine in 71 ml of toluene are heated to 900C and, at this temperature, 40 g of 2,4-di- |i chLoro-5-fLuorobenzoyl chloride are added dropwise in min.
The mixture is then stirred for 15 min, and the precipitated N,N-dimethylbenzylamine hydrochloride is separated off through a suction filter funnel.
The filtrate is substantially evaporated in vacuo, Sand 80 ml of butylglycol are added to the residue.
13 g of cyclopropylamine are added dropwise at 700-75 0 C in 30 min and, after addition is complete, the mixture is maintained at 100 0 C for 1 hour until the evolution of gas ceases.
27.9 g of potassium carbonate and 100 ml of butylglycol are added to the reaction mixture, which is then Le A 25 272 9 slowly heated to 135-1450C.
During this, about 40 mL of Low-boiling constituents distil out.
The temperature is maintained for 1.5 h.
It is then cooled to 100-1200C, and 130 mL of water are added to the reaction mixture.
The mixture is stirred at 90 0 C for 15 min and, at this temperature, 27 mL of acetic acid are added dropwise in 15 min. The contents of the flask are cooled, and the solid is separated off through a suction filter funnel.
The product is washed with 27 ml of water and 50 ml of methanol, sucked thoroughly dry and dried at 700C in vacuo for 24 h.
Yield: 37 g 74.9% of theory.
Example 2 43.2 g of ethyl N,N-dimethylamino-acryLate in 84 ml of toluene are heated to 100 C, and 40 ml of triethylamine are added.
At the reflux temperature, 60 g of 2,4-dichloro-5fluorobenzoyl chloride are added dropwise in 30 min, and then the precipitated triethylamine hydrochloride is separated off through a suction filter funnel.
t After washing with 65 ml of toluene, 16.2 g of 2' 5 cyclopropylamine are added dropwise to the filtrate at 0 C in 20 min.
The mixture is heated at 100 0 C until evolution of gas ceases.
Then 42 g of potassium carbonate and 270 ml of butylglycol are added, and the mixture is slowly heated to 135-145 0 C. During this, about 180 ml of toluene and low-boiling constituents distil out.
135-1450C are maintained for 1.5 h and, after the reaction mixture has been cooled to 100 0 C, 200 ml of water are added.
After 15 min, 40.5 ml of acetic acid are added Le A 25 272 10 dropwise at 90 0 C, and the precipitated solid is filtered off with suction through a suction filter funnel.
The product is then washed with 140 ml of water and 75 ml of methanol, thoroughly sucked dry and dried at 70 0 C in vacuo for 24 h.
Yield: 58.5 g 79% of theory.
Example 3 44.7 g of ethyl N,N-dimethylaminoacrylate and 17.1 g of N,NLdimethylpiperazine in 95 ml of cyclohexane are heated to reflux.
62 g of 2,4-dichloro-5-fluoro-benzoyl chloride are added dropwise in 1 h.
The precipitated dimethylbenzylamine hydrochloride is separated off through a suction filter funnel, and the filtrate is evaporated to dryness in vacuo.
The residue is dissolved in 125 ml of butylglycol and, at 90 C, 20.2 g of cyclopropylamine are added dropwise to the solution.
After the evolution of gas ceases, 43.4 g of potassium carbonate and 165 ml of butylglycol are added, and the mixture is heated at 1450C for 1.5 h. Initially t during this small amounts of Low-boiling constituents distil out.
l After 1.5 h, the mixture is cooled to 1000C, 205 ml of water are added, and the mixture is then stirred at 950C for 15 min.
Then 42 g of acetic acid are added dropwise in min, the temperature is reduced to 300C, and the precipitated solid is separated off on a suction filter funnel.
The filter cake is washed with 180 ml of water and 80 ml of 80% strength isopropanol and is dried at 70 0
C
in vacuo overnight.
Yield: 60.1 g 78.1% of theory.
35 Example 4 33.7 g of methyl N,N-dimethylamino-acrylate are Le A 25 272 11
I
heated with 40.5 g of N,N-dimethylbenzylamine in 95 ml of toluene at 110°C.
At the reflux temperature, 62 g of 2,4-dichloro-5fluorobenzoyl chloride are added dropwise in 1 h, and then the precipitated dimethylbenzylamine hydrochloride is removed through a suction filter funnel.
The solvent is distilled off in vacuo, 130 ml of butyLglycol are added and, at 90 0 C, 20.2 g of cyclopropylamine are added dropwise in 20 min.
After the evolution of gas ceases, 43.4 g of potassium carbonate and 150 ml of butylglycol are added to the reaction mixture which is then slowly heated to 1400C. During this, small amounts of low-boiling solvent distil out.
The mixture is then stirred at 1400C for 1.5 h.
After cooling to 100 0 C, 205 ml of water are added to the reaction mixture and it is then stirred at 900C for min.
While cooling slightly, 100 ml of 30% strength 20 sulphuric acid are added, and the solid is filtered off with suction on a suction filter funnel and is washed with i 200 ml of water and 200 ml of isopropanol.
The solid is dried in vacuo at 70°C overnight.
I Yield: 59.4 g 77.2% of theory.
25 Example i 55.6 g of tributylamine are added to 44.7 g of ethyl N,N-dimethylamino-acrylate in 95 ml of cyclohexane and, at 85-95 0 C, 62 g of 2,4-dichloro-5-fluorobenzoyl Schloride are added dropwise in 1 h.
Then 250 ml of water are added to the reaction mixture, and the aqueous salt phase is separated off.
The aqueous phase is extracted 1 x more by stirring with 50 ml of cyclohexane, and the combined org.
phases are evaporated to dryness under water pump vacuum.
The .esidue is taken up in 125 ml of butylglycol, and the mixture is heated to 70 0 C and 20.2 g of Le A 25 272 -12- 41 cyclopropylamine are added dropwise in 15 min.
After the evolution of gas ceases, a further 160 ml of butylglycol and 44 g of potassium carbonate are added, and the mixture is slowly heated to 1400C.
After the mixture has reached 1400C, it is stirred for 1.5 h and then cooled to 1000C, and 205 ml of water are added.
After 15 min, 42 g of acetic acid are added dropwise in 10 min, and the mixture is cooled to room temperature.
The precipitate is isolated through a suction fitter funnel and is washed with water and isopropanol.
The yield obtained after drying at 500C in vacuo overnight is 54.6 g 71% of theory.
Example 6 1i 105 g of tributylamine and 86 g of methyl N,Ndimethylamino-acrylate in 148 ml of toluene are heated to 105 0 C, and 124 g of 2,4-dichloro-5-fluoro-benzoyl chloride are added dropwise in 1 h.
After the reaction mixture has been cooled to 5 0
°C,
Sit is extracted 2 x with 250 ml of water each time.
The organic phase is substantially concentrated under water pump vacuum, and 37.5 g of cyclopropylamine are added dropwise to the residue at an internal tempera- 25 ture of 70-75 0 C. This results in gaseous dimethylamine Sescaping until the reaction is complete.
I86.8 g of potassium carbonate and 500 ml of butylglycol are added to the reaction mixture which is then slowly heated to 135 145 0 C. During this, small amounts o 30 of low-boiling solvents distil out.
135 145 0 C are maintained for 1.5 h, and then the mixture is cooled to 100 0 C, and 535 ml of a 10% strength acetic acid are added dropwise.
us The resulting suspension is cooled to room temperature, and the solid is separated off through a suction filter funnel and washed with 175 ml of water and 200 ml Le A 25 272 13 of 80% strength isopropanol.
The product is dried in vacuo at 700 C overnight.
YieLd: 220 g 78.1% of theory.
Le A 25 272 14 'I C
Claims (7)
1. Process for the preparation of quinolonecarboxy- lic acids of the general formula I X 4 0 3 1OOH X 2 Xi 1 in which 1 R represents propyl, cycLopropyl, isopropyl or vinyL, x denotes fluorine, chlorine, Br, CN, NO 2 or hydrogen, and X 2 X 3 and X represent fluorine, chlorine, N02 or hydrogen, characterized in that a compound of the formula 11 44 I 4 1 0 4C I :OCI C(I) t in which 1 4 X to X have the abovementioned meaning, and halogen, in particular chlorine or fluorine, is reacted, without isolation of intermediate stages in a so-called one-pot reaction, with a compound of the for- mula (III) £4 I I CH-COOR 2 CH-NR3R3 (III) 04 000cC~ in which Le A 25 272 15 -t 2 3 R and R are identical or different and rep- resent C 1 -C 4 -alkyl, in the presence of a solvent and of a base, where approp- riate heating to 500C to 150 0 C, to give the compounds of the formula IV X0 S 4 O 0 l II 2 X 3 -C-C-OR 2 KV CHNR 3 R 3 X2 X 5 x 2 X1 these compounds IV are subjected to an amine exchange at i temperatures of 50 0 C to 120 0 C in the presence of the i abovementioned solvents and in the presence of an amine i' of the formula R 1 NH 2 in which R 1 has the abovementioned meaning, resulting in the compounds of the formula X 4 0 0 II II X3 C-C-C-OR 2 V) x 2 CH-NH-R 1 X2 I X 5 X1 having the abovementioned radical meanings, and sub- S'sequently the compounds V are cyclized and hydrolysed at temperatures between 800C and 1800C in the presence of a base, and the compounds of the formula I are precipitated by addition of acid.
2. Process for the preparation of quinolonecarboxylic Sacids of the general formula I SX 4 0 X 3 #COOH (I) X 2 X 1 R 1 in which Le A 25 272 16 R represents cyclopropyL, X denotes fluorine, chlorine, Br, CN, N02 or hydrogen, and X X and X represent fluorine, chlorine, N02 or hydrogen, characterized in that a compound of the formula II X 4 X 3 COC1 X2 I x 2 in which X to X have the abovementioned meaning, and represents halogen, in particular chlorine or fluorine, is reacted, without isolation of intermediate stages in a so-called one-pot reaction, with a compound of the for- mula (III) 1 CH-COOR 2 CH-NRR 3 3 I in which S R 2 and R 3 are identical or different and rep- resent C 1 -C 4 -alkyl, 1 in the presence of a solvent and of a base, where approp- riate heating to 500C to 1500C, to give the compounds of the formula IV X4 0 0 II ii II (IV) I IX IHNR3R3 X 2 X X 1 Le A 25 272 17 ~rer~l~iwrrr these compounds IV are subjected to an amine exchange at temperatures of 50 0 C to 120 0 C in the presence of the abovementioned solvents and in the presence of cyclopro- pylamine, resulting in the compounds of the formula (V) having the abovementioned radical meanings, and sub- sequently the compounds V are cyclized and hydrolysed at temperatures between 800C and 1800C in the presence of a base, and the compounds of the formula I are precipitated by addition of acid.
3. Process for the preparation of lic acids of the general formula I quinolonecarboxy- SI (I) in which R represents cyclopropyl, X 1 X and X are identical or different and represent fluorine or chlorine, and X represents hydrogen, characterized in that a compound of the formula II (II) Le A 25 272 18 in which X to X have the abovementioned meaning, and X 5 represents halogen, in particular chlorine or fluorine, is reacted, without isolation of intermediate stages in a so-called one-pot reaction, with a compound of the for- mula (III) CH-COOR 2 II (III) CH-NR 3 R 3 in which R 2 and R 3 are identical or different and rep- resent C 1 -C 4 -alkyl, in the presence of a solvent and of a base, where approp- riate heating to 500C to 1500C, to give the compounds of the formula IV X 4 O 0 II Ii X3 C-C-C-OR 2 S. II (IV) CHNR 3 R3 ,X2 X 5 X1 these compounds IV are subjected to an amine exchange at temperatures of 50 0 C to 120 0 C in the presence of the abovementioned solvents and in the presence of cyclopro- pylamine, resulting in the compounds of the formula X 4 0 0 II II X3 C-C-C-OR 2 (V) CH -NH-< X 2 X X! having the abovementioned radical meanings, and sub- sequently the compounds V are cyclized and hydrolysed at temperatures between 80°C and 180°C in the presence of a Le A 25 272 19 Sbase, and the compounds of the formula I are precipitated by addition of acid.
4. Process for the preparation of quinolonecarboxylic acids of the general formula I X 4 o X3 cann (I) II'^ Y r-n 1 in which R represents cyclopropyl, 1 4 X and X denote hydrogen, X 3 represents fluorine, and X 2 denotes chlorine, characterized in that a compound of the formula II (II) in which X to X have the abovementioned meaning, and X represents halogen, in particular chlorine or fluorine, is reacted, without isolation of intermediate stages in a so-called one-pot reaction, with a compound of the for- mula (III) CH-COOR 2 II 3 CH-NRR (I in which R and R are identical or different and rep- resent C 1 -C 4 -alkyl, Le A 25 272 20 ~I 1 i in the prese i riate heatir i the formula nce of a solvent and of a base, where approp- ig to 500C to 1500C, to give the compounds of IV 0 I -C-C-OR 2 'I CHNR 3 R 3 X
5 (IV) these compounds IV are subjected to an amine exchange at temperatures of 50 0 C to 120 0 C in the presence of the abovementioned solvents and in the presence of cyclopro- pylamine, resulting in the compounds of the formula X 4 0 0 X3 -C-C-OR 2 x 2 gH-NH-R, X 1 having the abovementioned radical meanings, and sub- sequently the compounds V are cyclized and hydrolysed at temperatures between 800C and 1800C in the presence of a base, and the compounds of the formula I are precipitated by addition of acid. Process for the preparation of quinolonecarboxy- lic acids of the general formula I X 4 0 X3 1 1o OOH X 2 X 1 R 1 (1) in which R represents cyclopropyl, X and X 2 represent chlorine, and X 3 denotes fluorine, and Le A 25 272 -21 7 X denotes hydrogen, which is characterized in that a compound of the formuLa 11 I) in which X to X have the abovementioned meaning, and X represents halogen, in particular chlorine or fluorine, is reacted, without isolation of intermediate stages in a so-called one-pot reaction, with a compound of the for- mula (III) CH-COOR 2 I1 CH-NR 3 R 3 (III) 1: rt r r re r Iv Z I Ii in which R 2 and R 3 are identical or different and rep- resent C 1 -C 4 -alkyl, in the presence of a solvent and of a base, where approp- riate heating to 500C to 1500C, to give the compounds of the formula IV (IV) these compounds IV are subjected to an amine exchange at temperatures of 500C to 120°C in the presence of the abovementioned solvents and in the presence of cycLopro- pylamine, resulting in the compounds of the formula Le A 25 272 22 i II II SX3 C-C-C-OR 2 I II CH-NH-R (V) SX 2 X X having the abovementioned radical meanings, and subsequently the compounds V are cyclized and hydrolysed at temperatures between 80°C and 180 0 C in the presence of a base, and the *0 9 S compounds of the formula I are precipitated by addition of acid. 0000
6. A process as claimed by any one of claims 1 to 00 substantially as herein described with reference to any one of the foregoing examples thereof.
7. Quinolonecarboxylic acids of formula I as shown in claim 1, whenever prepared by the process defined in any one of 0 0 0 0 claims 1 to 6. 00 6 0 o 000 DATED this 13th day of July, 1990. BAYER AKTIENGESELLSCHAFT By Its Patent Attorneys ARTHUR S. CAVE CO. T. 23 2039F/AC
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19873724466 DE3724466A1 (en) | 1987-07-24 | 1987-07-24 | PROCESS FOR THE PREPARATION OF CHINOLON CARBOXYANESE |
| DE3724466 | 1987-07-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1902488A AU1902488A (en) | 1989-01-27 |
| AU602226B2 true AU602226B2 (en) | 1990-10-04 |
Family
ID=6332237
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU19024/88A Expired AU602226B2 (en) | 1987-07-24 | 1988-07-14 | New preparation process |
Country Status (23)
| Country | Link |
|---|---|
| EP (1) | EP0300311B1 (en) |
| JP (1) | JP2812956B2 (en) |
| KR (1) | KR970010175B1 (en) |
| CN (1) | CN1030911A (en) |
| AR (1) | AR243509A1 (en) |
| AT (1) | ATE111898T1 (en) |
| AU (1) | AU602226B2 (en) |
| CA (1) | CA1333715C (en) |
| DD (1) | DD281806A5 (en) |
| DE (2) | DE3724466A1 (en) |
| DK (1) | DK174855B1 (en) |
| ES (1) | ES2058186T3 (en) |
| FI (1) | FI883452A (en) |
| HU (1) | HU205082B (en) |
| IE (1) | IE63654B1 (en) |
| IL (1) | IL87185A (en) |
| NO (1) | NO174773C (en) |
| NZ (1) | NZ225502A (en) |
| PH (1) | PH25098A (en) |
| PT (1) | PT88078B (en) |
| SU (1) | SU1660582A3 (en) |
| UA (1) | UA8018A1 (en) |
| ZA (1) | ZA885332B (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5093515A (en) * | 1987-08-14 | 1992-03-03 | Asahi Glass Company Ltd. | Fluorinated benzoyl compounds |
| DE4015299A1 (en) * | 1990-05-12 | 1991-11-14 | Bayer Ag | METHOD FOR PRODUCING 3-AMINO-2- (HET) -AROYL-ACRYLIC ACID DERIVATIVES |
| ES2039301B1 (en) * | 1991-11-20 | 1994-05-16 | Genesis Para La Investigacion | PROCEDURE FOR OBTAINING NEW USEFUL SYNTHESIS INTERMEDIATES FOR THE PREPARATION OF FLUOROQUINOLONS. |
| DE4342186A1 (en) * | 1993-12-10 | 1995-06-14 | Bayer Ag | One-pot process for the production of 3-quinolonecarboxylic acid derivatives |
| KR100242355B1 (en) * | 1994-08-02 | 2000-03-02 | 데이비드 엠 모이어 | Method for producing antimicrobial compound |
| DE19826050A1 (en) * | 1998-06-12 | 1999-12-16 | Bayer Ag | Process for the preparation of quinolonic and naphthyridonecarboxylic acids and their esters |
| ES2203254T3 (en) * | 1998-11-18 | 2004-04-01 | Asahi Glass Company Ltd. | DERIVATIVES OF AMINOACRYLIC ACID AND CORRESPONDING PRODUCTION PROCEDURE. |
| US20080139574A1 (en) | 2006-11-30 | 2008-06-12 | Cadila Healthcare Limited | Novel quinoline derivatives |
| CN101781299B (en) * | 2010-01-13 | 2012-06-27 | 杭州师范大学 | One-pot synthesis method for key intermediate of carbostyril medicaments |
| CN104292159B (en) * | 2014-10-10 | 2016-12-07 | 浙江同丰医药化工有限公司 | A kind of preparation method of norfloxacin, ciprofloxacin and enrofloxacin |
| CN111269131B (en) * | 2020-03-12 | 2021-12-28 | 江苏飞宇医药科技股份有限公司 | Process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as acid acceptor |
| CN115385856A (en) * | 2022-09-05 | 2022-11-25 | 常州大学 | Method for synthesizing norfloxacin intermediate by one-pot method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4917785A (en) * | 1984-11-15 | 1986-05-22 | Bayer Aktiengesellschaft | Alkyl-1-cyclopropyl -1, 4-dihydro-4-oxo-quinoline carboxylic acids, preparation and antibacterial agent thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2808070A1 (en) * | 1978-02-24 | 1979-08-30 | Bayer Ag | PROCESS FOR THE PRODUCTION OF 4-PYRIDONE-3-CARBONIC ACIDS AND / OR DERIVATIVES |
| DE3142854A1 (en) * | 1981-10-29 | 1983-05-11 | Bayer Ag, 5090 Leverkusen | 1-CYCLOPROPYL-6-FLUOR-1,4-DIHYDRO-4-OXO-7-PIPERAZINO-CHINOLINE-3-CARBONIC ACIDS, METHOD FOR THE PRODUCTION THEREOF AND THEIR CONTAINING ANTIBACTERIAL AGENTS |
| DE3318145A1 (en) * | 1983-05-18 | 1984-11-22 | Bayer Ag, 5090 Leverkusen | 7-AMINO-1-CYCLOPROPYL-6,8-DIFLUOR-1,4-DIHYDRO-4-OXO-3-CHINOLINE CARBONIC ACIDS, METHOD FOR THE PRODUCTION THEREOF AND THEIR CONTAINING ANTIBACTERIAL AGENTS |
| DE3426486A1 (en) * | 1984-07-18 | 1986-01-30 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING CHINOLONIC AND NAPHTHYRIDONE CARBONIC ACIDS |
| UA7018A1 (en) * | 1984-09-29 | 1995-03-31 | "Байер АГ" | METHOD OF OBTAINING ACRYLIC ACID DERIVATIVES |
| DE3502935A1 (en) * | 1984-09-29 | 1986-04-10 | Bayer Ag, 5090 Leverkusen | 3-AMINO-2-BENZOYL-ACRYLIC ACID DERIVATIVES AND A METHOD FOR THE PRODUCTION THEREOF |
| JPS6259263A (en) * | 1985-09-10 | 1987-03-14 | Kyorin Pharmaceut Co Ltd | Quinolonecarboxylic acid derivative |
-
1987
- 1987-07-24 DE DE19873724466 patent/DE3724466A1/en not_active Withdrawn
-
1988
- 1988-07-01 PH PH37150A patent/PH25098A/en unknown
- 1988-07-07 NO NO883046A patent/NO174773C/en not_active IP Right Cessation
- 1988-07-11 DE DE3851588T patent/DE3851588D1/en not_active Expired - Lifetime
- 1988-07-11 ES ES88111034T patent/ES2058186T3/en not_active Expired - Lifetime
- 1988-07-11 AT AT88111034T patent/ATE111898T1/en not_active IP Right Cessation
- 1988-07-11 EP EP88111034A patent/EP0300311B1/en not_active Expired - Lifetime
- 1988-07-14 AU AU19024/88A patent/AU602226B2/en not_active Expired
- 1988-07-20 UA UA4356111A patent/UA8018A1/en unknown
- 1988-07-20 SU SU88A patent/SU1660582A3/en active
- 1988-07-21 FI FI883452A patent/FI883452A/en not_active Application Discontinuation
- 1988-07-21 IL IL87185A patent/IL87185A/en not_active IP Right Cessation
- 1988-07-21 NZ NZ225502A patent/NZ225502A/en unknown
- 1988-07-21 JP JP63180478A patent/JP2812956B2/en not_active Expired - Lifetime
- 1988-07-21 AR AR88311472A patent/AR243509A1/en active
- 1988-07-22 PT PT88078A patent/PT88078B/en not_active IP Right Cessation
- 1988-07-22 DD DD88318209A patent/DD281806A5/en not_active IP Right Cessation
- 1988-07-22 ZA ZA885332A patent/ZA885332B/en unknown
- 1988-07-22 CA CA000572825A patent/CA1333715C/en not_active Expired - Lifetime
- 1988-07-22 DK DK198804124A patent/DK174855B1/en not_active IP Right Cessation
- 1988-07-22 HU HU883878A patent/HU205082B/en unknown
- 1988-07-22 IE IE225588A patent/IE63654B1/en not_active IP Right Cessation
- 1988-07-23 KR KR88009300A patent/KR970010175B1/en not_active IP Right Cessation
- 1988-07-23 CN CN88104633A patent/CN1030911A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU4917785A (en) * | 1984-11-15 | 1986-05-22 | Bayer Aktiengesellschaft | Alkyl-1-cyclopropyl -1, 4-dihydro-4-oxo-quinoline carboxylic acids, preparation and antibacterial agent thereof |
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