CA1095056A - Process for the manufacture of isoxazole derivatives - Google Patents
Process for the manufacture of isoxazole derivativesInfo
- Publication number
- CA1095056A CA1095056A CA292,253A CA292253A CA1095056A CA 1095056 A CA1095056 A CA 1095056A CA 292253 A CA292253 A CA 292253A CA 1095056 A CA1095056 A CA 1095056A
- Authority
- CA
- Canada
- Prior art keywords
- fluorine
- formula
- carbon atoms
- represent
- chlorine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members 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
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Abstract of the Disclosure:
A process for the preparation of 5-methyl-isoxazole-4-carboxylic acid anilides of the formula in which an aniline of the formula is reacted with a 5-methyl-isoxazole derivative of the formula
A process for the preparation of 5-methyl-isoxazole-4-carboxylic acid anilides of the formula in which an aniline of the formula is reacted with a 5-methyl-isoxazole derivative of the formula
Description
-` ~0~0S6 Our copending Canadian Patent Application No. 254,134 relates to 5-methyl-isoxazole-4-carboxylic acid anilides of the formula I CONH ~ 2 ~ C~3 (I) in which Rl, R2 and R3 can be identical or different and denote alkyl having 1, 2 or 3 C atoms, alkoxy having 1, 2 or 3 C atoms, alkylthio having 1, 2 or 3 C atoms, each of which groups can be completely or partially substituted by identical or different halogen atoms, such as fluorine, chlorine, bromine or iodine, or denote halogen, such as fluorine, chlorine, bromine or iodine, or nitro, cyano or carbalkoxy having 1, 2 or 3 C atoms in the alkyl group, and in which Rl and R2 also denote hydrogen, in which case, however, R3 cannot be methyl, but in which case R3 additionally denotes phenyl which may be monosubstituted or disubstituted by any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 C atoms or alkoxy having 1, 2 or 3 C atoms, ox phenoxy which may be monosubstituted or disubstituted by any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 C atoms or alkoxy having 1, 2 or 3 C atoms, or in which Rl denotes hydrogen and R2 and R3 conjointly denote a methylenedioxy group or, con-jointly with the phenyl ring carrying them, denote a naphthalene ring, and, furthermore, it relates to a process for the manufac-ture of the compounds of the formula I, wherein an acetoacetic acid anilide of the formula II
/~=~y, R3 CH3-CO-CH~-CONH ~ R2 (II) ~3~
.
0~5~S6 in which Rl, R2 and R3 have the abovementioned meaning, is warmed with an orthoformic acid ester of the formula III
HC (OR)3 (III) in which R denotes a Cl- to C4- alkyl, and advantageously with an acid anhydride, the resulting 2-alkoxymethylene-acetoacetic acid anilide of the formula IV
~ R3 CH3-CO-IC-CONH ~ R2 (IV) ~ ~ OR Rl in which R, R1, R2 and R3 have the abovementioned meanings, is isolated and this is subsequently treated with hydroxylamine in an organic solvent.
In a further development of the process according to the aforesaid specification, a simplified process for the manufacture of 5-methyl-isoxazole-4-carboxylic acid anilides of the formula I
CONH~ ~ I ) CH R
in which Rl, R2 and R3 can be identical or different and denote alkyl having 1, 2 or 3 C atoms, alkoxy having 1, 2 or 3 C atoms, alkylthio having 1, 2 or 3 C atoms, each of which groups can be completely or partially substituted by identical or different halogen atoms, such as fluorine, chlorine, bromine or iodine, or denote halogen, such as fluorine, chlorine, bromine or iodine, or nitro, cyano or carbalkoxy having 1, 2 or 3 C atoms in the alkyl group, and in which Rl and R2 also denote hydrogen, in which case, however, R3 cannot be methyl, but in which case R3 additionally denotes phenyl which may be monosubstituted or disubstituted by .
any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 C atoms or alkoxy having 1, 2 or 3 C atoms, or phenoxy which may be monosubstituted or disubstituted by any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 C atoms or alkoxy having 1, 2 or 3 C atoms, or in which Rl denotes hydrogen and R2 and R3 conjointly denote a methylenedioxy group or, con-jointly with the phenyl ring carrying them, denotes a naphthalene ring, has now been found, wherein an aniline of the formula V
~ ~ ~2 (V) in which Rl, R2 and R3 have the abovementioned meanings, is reacted with a 5-methylisoxazole derivative of the formula VI
~;o ~ C ~ X (VI) ~ ~ CH
in which X denotes a halogen atom, preferably chlorine or bromine, a YO- group or a ZO-CO-O- group, Y representing phenyl which may be monosubstituted, disubstituted or trisubstituted by fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy, ethoxy, nitro or cyano, or the acyl radical corresponding to the formula V and Z representing (Cl-C4)-alkyl, benzyl or phenyl.
Advantageously, the reaction is carried out in a parti-tioning agent or solvent which has an inert behaviour towards the reactants. For example, these can be nitriles, such as acetoni-trile, ethers, such as diethyl ether, tetrahydrofurane or dioxane, and alcohols, such as methanol, ethanol, propanol or isopropanol.
A preferred process forthe preparation of the compounds ::
,` .
05~
of the formula I is the reaction ofthe carboxylic acid chloride of the formula VI with an aniline of the formula V. It is advan-tageous here to carry out the reaction in the presence of acid binding agents, such as potassium carbonate or sodium carbonate, alkali metal or alkaline earth metal hydroxides or alcoholates, organic bases, for example triethylamine, pyridine, picoline or quinoline or an excess of the particular aniline employed, at temperatures between 0 and 160C, preferably between 20 and 80C.
The reaction times can be from a few minutes up to two hours.
The 5-methylisoxazole-4-carboxylic acid derivatives of the formula VI, required as starting materials for the process according to theinvention, are obtained in a manner which is in itself known (compare German Patent 634,286) by reaction of ethoxymethylideneacetoacetic acid ester with hydroxylamine to give a 5-methyl-isoxazole-4-carboxylic acid ester, by acid saponi-fication of the ester thus obtained, preferably using a mixture of glacial acetic acid and concentrated hydrochloric acid in a ratio of 1:1, to give 5-methyl-isoxazole-4-carboxylic acid and by conversion of this carboxylic acid by customary methods into the carboxylic acid halides, esters or anhydrides. The 5-methyl-isoxazole-4-carboxylic acids can also be activated by reaction with a carbodiimide, for example dicyclohexylcarbodiimide.
Possible carboxylic acid derivatives of the formula ~I
are 5-methylisoxazole-4-carboxylic acid phenyl ester, in particu-lar also the 2,4-dichloro-phenyl ester and the 2,4,6-trichloro-phenyl ester, and furthermore 5-methylisoxazole-4-carboxylic acid anhydrides, in particular those in which X denotes the methoxycarbonyloxy radical, the ethoxycarbonyloxy radical or the l~S05~
benzyloxycarbonyloxy radical.
The compounds of the formula I are pharmacologically active. They have a strong antiphlogistic and analgesic action.
Preparation examples 1. 5-methylisoxazole-4-carboxylic acid 4-fluoro-anilide of the formula I
al) A solution of 7.3 g (0.05 mole) of 5-methylisoxazole-4-carboxylic acid chloride of the formula VI in 20 ml of acetoni-trile is added dropwise, whilst stirring, at room temperature to 0.1 mole of 4-fluoroaniline of the formula V (11.1 g), dissolved in 200 ml of acetonitrile. After stirring for a further 15 minutes, the crystals which have precipitated are filtered off and rinsed with twice 20 ml of acetonitrile and the combined filtrates are brought to dryness under reduced pressure. This gives 10.8 g (98% of theory) of an oily residue which crystal-lizes after trituration.
Melting point after recrystallization from water:
117 to 118C.
a2) When 0.05 mole of triethylamine (10.1 g) is used as the acid-binding agent instead of the 4-fluoroaniline of the formula V, the oily residue is digested with water. The crystals thus obtained are filtered off and washed with water. ~ft~r dry-ing in air, this gives 10.6 g (96% of theory~ of colorless crystals whichj after recrystallization from water, melt at 117 to 118C.
b) 0.1 mole of 4-fluoroaniline of the formula V ( 11.1 g) and 0.1 mole of 4-bromophenyl 5-methylisoxazole-4-carboxylate of the formula Vl (28.2 g) dissolved in 50 ml of acetonitrile are heated under reflux for 90 minutes. Subsequently the solution . .
, , :
is evaporated under reduced pressure and the residue is digested with petroleum ether. This gives 15.6 g (71% of theory) of an oily residue which crystallizes after spreading out. Melting point after recrystallization from water: 117 to 11~C.
c) 0.1 mole of 4-fluoroaniline of the formula V (11.1 g) and 0.1 mole of ethoxycarbonyl 5-methylisoxazole-4-carboxylate of the formula VI (19.9 g), dissolved in 60 ml of tetrahydro-furane, are heated under reflux for 60 minutes. The reaction mixture is then brought to dryness and this gives 17.1 g (78% of theory) of a crystalline residue which, after recrystallization from water, melts at 117 to 118C.
The compounds listed in Table 1 were prepared by the process indicated above.
Table 1: 5-methylisoxazole-4-carboxylic acid anilides of the formula I
No. Rl R2 R3Melting point C
/~=~y, R3 CH3-CO-CH~-CONH ~ R2 (II) ~3~
.
0~5~S6 in which Rl, R2 and R3 have the abovementioned meaning, is warmed with an orthoformic acid ester of the formula III
HC (OR)3 (III) in which R denotes a Cl- to C4- alkyl, and advantageously with an acid anhydride, the resulting 2-alkoxymethylene-acetoacetic acid anilide of the formula IV
~ R3 CH3-CO-IC-CONH ~ R2 (IV) ~ ~ OR Rl in which R, R1, R2 and R3 have the abovementioned meanings, is isolated and this is subsequently treated with hydroxylamine in an organic solvent.
In a further development of the process according to the aforesaid specification, a simplified process for the manufacture of 5-methyl-isoxazole-4-carboxylic acid anilides of the formula I
CONH~ ~ I ) CH R
in which Rl, R2 and R3 can be identical or different and denote alkyl having 1, 2 or 3 C atoms, alkoxy having 1, 2 or 3 C atoms, alkylthio having 1, 2 or 3 C atoms, each of which groups can be completely or partially substituted by identical or different halogen atoms, such as fluorine, chlorine, bromine or iodine, or denote halogen, such as fluorine, chlorine, bromine or iodine, or nitro, cyano or carbalkoxy having 1, 2 or 3 C atoms in the alkyl group, and in which Rl and R2 also denote hydrogen, in which case, however, R3 cannot be methyl, but in which case R3 additionally denotes phenyl which may be monosubstituted or disubstituted by .
any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 C atoms or alkoxy having 1, 2 or 3 C atoms, or phenoxy which may be monosubstituted or disubstituted by any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 C atoms or alkoxy having 1, 2 or 3 C atoms, or in which Rl denotes hydrogen and R2 and R3 conjointly denote a methylenedioxy group or, con-jointly with the phenyl ring carrying them, denotes a naphthalene ring, has now been found, wherein an aniline of the formula V
~ ~ ~2 (V) in which Rl, R2 and R3 have the abovementioned meanings, is reacted with a 5-methylisoxazole derivative of the formula VI
~;o ~ C ~ X (VI) ~ ~ CH
in which X denotes a halogen atom, preferably chlorine or bromine, a YO- group or a ZO-CO-O- group, Y representing phenyl which may be monosubstituted, disubstituted or trisubstituted by fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy, ethoxy, nitro or cyano, or the acyl radical corresponding to the formula V and Z representing (Cl-C4)-alkyl, benzyl or phenyl.
Advantageously, the reaction is carried out in a parti-tioning agent or solvent which has an inert behaviour towards the reactants. For example, these can be nitriles, such as acetoni-trile, ethers, such as diethyl ether, tetrahydrofurane or dioxane, and alcohols, such as methanol, ethanol, propanol or isopropanol.
A preferred process forthe preparation of the compounds ::
,` .
05~
of the formula I is the reaction ofthe carboxylic acid chloride of the formula VI with an aniline of the formula V. It is advan-tageous here to carry out the reaction in the presence of acid binding agents, such as potassium carbonate or sodium carbonate, alkali metal or alkaline earth metal hydroxides or alcoholates, organic bases, for example triethylamine, pyridine, picoline or quinoline or an excess of the particular aniline employed, at temperatures between 0 and 160C, preferably between 20 and 80C.
The reaction times can be from a few minutes up to two hours.
The 5-methylisoxazole-4-carboxylic acid derivatives of the formula VI, required as starting materials for the process according to theinvention, are obtained in a manner which is in itself known (compare German Patent 634,286) by reaction of ethoxymethylideneacetoacetic acid ester with hydroxylamine to give a 5-methyl-isoxazole-4-carboxylic acid ester, by acid saponi-fication of the ester thus obtained, preferably using a mixture of glacial acetic acid and concentrated hydrochloric acid in a ratio of 1:1, to give 5-methyl-isoxazole-4-carboxylic acid and by conversion of this carboxylic acid by customary methods into the carboxylic acid halides, esters or anhydrides. The 5-methyl-isoxazole-4-carboxylic acids can also be activated by reaction with a carbodiimide, for example dicyclohexylcarbodiimide.
Possible carboxylic acid derivatives of the formula ~I
are 5-methylisoxazole-4-carboxylic acid phenyl ester, in particu-lar also the 2,4-dichloro-phenyl ester and the 2,4,6-trichloro-phenyl ester, and furthermore 5-methylisoxazole-4-carboxylic acid anhydrides, in particular those in which X denotes the methoxycarbonyloxy radical, the ethoxycarbonyloxy radical or the l~S05~
benzyloxycarbonyloxy radical.
The compounds of the formula I are pharmacologically active. They have a strong antiphlogistic and analgesic action.
Preparation examples 1. 5-methylisoxazole-4-carboxylic acid 4-fluoro-anilide of the formula I
al) A solution of 7.3 g (0.05 mole) of 5-methylisoxazole-4-carboxylic acid chloride of the formula VI in 20 ml of acetoni-trile is added dropwise, whilst stirring, at room temperature to 0.1 mole of 4-fluoroaniline of the formula V (11.1 g), dissolved in 200 ml of acetonitrile. After stirring for a further 15 minutes, the crystals which have precipitated are filtered off and rinsed with twice 20 ml of acetonitrile and the combined filtrates are brought to dryness under reduced pressure. This gives 10.8 g (98% of theory) of an oily residue which crystal-lizes after trituration.
Melting point after recrystallization from water:
117 to 118C.
a2) When 0.05 mole of triethylamine (10.1 g) is used as the acid-binding agent instead of the 4-fluoroaniline of the formula V, the oily residue is digested with water. The crystals thus obtained are filtered off and washed with water. ~ft~r dry-ing in air, this gives 10.6 g (96% of theory~ of colorless crystals whichj after recrystallization from water, melt at 117 to 118C.
b) 0.1 mole of 4-fluoroaniline of the formula V ( 11.1 g) and 0.1 mole of 4-bromophenyl 5-methylisoxazole-4-carboxylate of the formula Vl (28.2 g) dissolved in 50 ml of acetonitrile are heated under reflux for 90 minutes. Subsequently the solution . .
, , :
is evaporated under reduced pressure and the residue is digested with petroleum ether. This gives 15.6 g (71% of theory) of an oily residue which crystallizes after spreading out. Melting point after recrystallization from water: 117 to 11~C.
c) 0.1 mole of 4-fluoroaniline of the formula V (11.1 g) and 0.1 mole of ethoxycarbonyl 5-methylisoxazole-4-carboxylate of the formula VI (19.9 g), dissolved in 60 ml of tetrahydro-furane, are heated under reflux for 60 minutes. The reaction mixture is then brought to dryness and this gives 17.1 g (78% of theory) of a crystalline residue which, after recrystallization from water, melts at 117 to 118C.
The compounds listed in Table 1 were prepared by the process indicated above.
Table 1: 5-methylisoxazole-4-carboxylic acid anilides of the formula I
No. Rl R2 R3Melting point C
2 H H 4-C1 151
3 H H 4-Br 162 - 163
4 H H 4-I 173 - 173.5 H 3-Cl 4-Cl 146 7 H _o 2125 - 126 : , ~0'~505~
The numbers in Table 1 denote:
1. 5-Methylisoxazole-4-carboxylic acid 4-fluoro-anilide 2. 5-Methylisoxazole-4-carboxylic acid 4-chloro-anilide 3. 5-Methylisoxazole-4-carboxylic acid 4-bromo-anilide 4. 5-Methylisoxazole-4-carboxylic acid 4-iodo-anilide
The numbers in Table 1 denote:
1. 5-Methylisoxazole-4-carboxylic acid 4-fluoro-anilide 2. 5-Methylisoxazole-4-carboxylic acid 4-chloro-anilide 3. 5-Methylisoxazole-4-carboxylic acid 4-bromo-anilide 4. 5-Methylisoxazole-4-carboxylic acid 4-iodo-anilide
5. 5-Methylisoxazole-4-carboxylic acid 3,4-dichloro-anilide
6. 5-Methylisoxazole-4-carboxylic acid 3-chloro-4-fluoro-anilide
7. 5-Methylisoxazole-4-carboxylic acid 3,4-methylenedioxy-anilide
8. 5-Methylisoxazole-4-carboxylic acid 3,4-difluoro-anilide
9. 5-Methylisoxazole-4-carboxylic acid 4-chloro-3-fluoro-anilide
10. 5-Methylisox~zole~4-carboxylic acid 2,4-difluoro-anilide
11. 5-Methylisoxazole-4-carboxy~ic acid 2-fluoro-5-trifluoro-methyl-anilide.
"
"
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the preparation of a 5-methyl-isoxazole-4-carboxylic acid anilide of the formula I
(I) wherein R1, R2 and R3 can be identical or different and represent alkyl having 1, 2 or 3 carbon atoms, alkoxy having 1, 2 or 3 carbon atoms, alkylthio having 1, 2 or 3 carbon atoms and each of these groups can be completely or partially substituted by identical or different halogen atoms, or R1, R2 and R3 represent halogen, nitro, cyano or carbalkoxy having 1, 2 or 3 carbon atoms in the alkyl group and in which R1 and R2 also represent hydrogen, in which case, however, R3 cannot be methyl, but in which case R3 additionally represents phenyl which may be monosubstituted or disubstituted by any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 carbon atoms or alkoxy having 1, 2 or 3 carbon atoms, or phenoxy which may be monosubstituted or disub-stituted by any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 carbon atoms or alkoxy having 1, 2 or 3 carbon atoms, or in which R1 represents hydrogen and R2 and R3 con-jointly represent a methylenedioxy group or, conjointly with the phenyl ring carrying them, represent a naphthalene ring, in which an aniline of the formula V
(V) wherein R1, R2 and R3 are as defined above, is reacted with a 5-methyl-isoxazole derivative of the formula VI
(VI) wherein X represents a halogen atom, a YO- group or a ZO-CO-O-group, Y representing phenyl which may be monosubstituted, disubstituted or trisubstituted by fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy, ethoxy, nitro or cyano; or the acyl radical corresponding to the formul V and Z representing (C1-C4)-alkyl, benzyl or phenyl.
(I) wherein R1, R2 and R3 can be identical or different and represent alkyl having 1, 2 or 3 carbon atoms, alkoxy having 1, 2 or 3 carbon atoms, alkylthio having 1, 2 or 3 carbon atoms and each of these groups can be completely or partially substituted by identical or different halogen atoms, or R1, R2 and R3 represent halogen, nitro, cyano or carbalkoxy having 1, 2 or 3 carbon atoms in the alkyl group and in which R1 and R2 also represent hydrogen, in which case, however, R3 cannot be methyl, but in which case R3 additionally represents phenyl which may be monosubstituted or disubstituted by any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 carbon atoms or alkoxy having 1, 2 or 3 carbon atoms, or phenoxy which may be monosubstituted or disub-stituted by any of fluorine, chlorine, bromine, iodine, alkyl having 1, 2 or 3 carbon atoms or alkoxy having 1, 2 or 3 carbon atoms, or in which R1 represents hydrogen and R2 and R3 con-jointly represent a methylenedioxy group or, conjointly with the phenyl ring carrying them, represent a naphthalene ring, in which an aniline of the formula V
(V) wherein R1, R2 and R3 are as defined above, is reacted with a 5-methyl-isoxazole derivative of the formula VI
(VI) wherein X represents a halogen atom, a YO- group or a ZO-CO-O-group, Y representing phenyl which may be monosubstituted, disubstituted or trisubstituted by fluorine, chlorine, bromine, iodine, methyl, ethyl, methoxy, ethoxy, nitro or cyano; or the acyl radical corresponding to the formul V and Z representing (C1-C4)-alkyl, benzyl or phenyl.
2. A process as claimed in claim 1 in which the preparation is carried out in the presence of an inert solvent.
3. A process as claimed in claim 1 in which a carboxylic acid chloride of the formula VI is reacted with an aniline of the formula V in the presence of an acid binding agent at a temperature in the range of from 0 to 160°C.
4. A process as claimed in claim 1, claim 2 or claim 3, in which R1 represents hydrogen, R2 represents fluorine and R3 represents fluorine, chlorine or trifluoromethyl.
5. A process as claimed in claim 1, claim 2 or claim 3, in which R1 represents hydrogen and R2 and R3 represent fluorine in the 3 and 4 positions.
6. A process as claimed in claim 1, claim 2 or claim 3, in which R1 represents hydrogen, R2 represents fluorine in the 3 position, and R3 represents chlorine in the 4 position.
7. A process as claimed in claim 1, claim 2 or claim 3, in which R1 represents hydrogen and R2 and R3 represent fluorine in the 2 and 4 positions.
8. A process as claimed in claim 1, claim 2 or claim 3 in which R1 represents hydrogen, R2 represents fluorine in the 2 position and R3 represents trifluoromethyl in the 5 position.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19762654797 DE2654797A1 (en) | 1976-12-03 | 1976-12-03 | PROCESS FOR THE PREPARATION OF ISOXAZOLE DERIVATIVES |
| DEP2654797.7 | 1976-12-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1095056A true CA1095056A (en) | 1981-02-03 |
Family
ID=5994582
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA292,253A Expired CA1095056A (en) | 1976-12-03 | 1977-12-02 | Process for the manufacture of isoxazole derivatives |
Country Status (14)
| Country | Link |
|---|---|
| JP (1) | JPS5371068A (en) |
| AT (1) | AT361917B (en) |
| BE (1) | BE861500R (en) |
| CA (1) | CA1095056A (en) |
| CH (1) | CH609341A5 (en) |
| DE (1) | DE2654797A1 (en) |
| DK (1) | DK538777A (en) |
| ES (1) | ES464533A2 (en) |
| FR (1) | FR2381756A2 (en) |
| GB (1) | GB1572309A (en) |
| IE (1) | IE46001B1 (en) |
| IT (1) | IT1089430B (en) |
| LU (1) | LU78614A1 (en) |
| NL (1) | NL7713083A (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55500866A (en) * | 1978-11-03 | 1980-10-30 | ||
| EP0035285A3 (en) * | 1979-08-17 | 1981-10-14 | American Cyanamid Company | Novel isoxazole carboxylic acid phenyl esters, pharmaceutical compositions containing certain of said esters, and process for preparing said esters |
| DE2854439A1 (en) * | 1978-12-16 | 1980-07-03 | Hoechst Ag | AN ISOXAZOLE DERIVATIVE, METHOD FOR THE PRODUCTION THEREOF, AGENT AND USE THEREOF |
| DE2854438A1 (en) * | 1978-12-16 | 1980-07-03 | Hoechst Ag | ISOXAZOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, MEANS CONTAINING THESE COMPOUNDS AND THEIR USE |
| PT71367A (en) * | 1979-06-11 | 1980-07-01 | Ciba Geigy Ag | Process for preparing alphacarbamoyl-pyrrolpropionitriles |
| DE3247454A1 (en) * | 1982-12-22 | 1984-06-28 | Laboratorios Bago S.A., Buenos Aires | Substituted 3-phenyl-5-methylisoxazole-4-carboxanilides, process for their preparation and pharmaceutical compositions containing these compounds |
| GB8619432D0 (en) * | 1986-08-08 | 1986-09-17 | Lilly Industries Ltd | Pharmaceutical compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES448386A1 (en) * | 1975-06-05 | 1978-04-16 | Hoechst Ag | 5-Methyl-isoxazole-4-carboxylic acid anilides |
| DE2525023A1 (en) * | 1975-06-05 | 1976-12-16 | Hoechst Ag | N-Halophenyl isoxazole-4-carboxamides - are fungicides useful in plant protection |
-
1976
- 1976-12-03 DE DE19762654797 patent/DE2654797A1/en not_active Withdrawn
-
1977
- 1977-11-15 CH CH1393277A patent/CH609341A5/en not_active IP Right Cessation
- 1977-11-28 ES ES464533A patent/ES464533A2/en not_active Expired
- 1977-11-28 NL NL7713083A patent/NL7713083A/en not_active Application Discontinuation
- 1977-12-01 IT IT3028677A patent/IT1089430B/en active
- 1977-12-01 LU LU78614A patent/LU78614A1/xx unknown
- 1977-12-02 DK DK538777A patent/DK538777A/en not_active Application Discontinuation
- 1977-12-02 AT AT866177A patent/AT361917B/en not_active IP Right Cessation
- 1977-12-02 IE IE245377A patent/IE46001B1/en unknown
- 1977-12-02 GB GB5034277A patent/GB1572309A/en not_active Expired
- 1977-12-02 FR FR7736424A patent/FR2381756A2/en active Granted
- 1977-12-02 CA CA292,253A patent/CA1095056A/en not_active Expired
- 1977-12-03 JP JP14561977A patent/JPS5371068A/en active Pending
- 1977-12-05 BE BE183167A patent/BE861500R/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2381756B2 (en) | 1982-10-29 |
| CH609341A5 (en) | 1979-02-28 |
| IT1089430B (en) | 1985-06-18 |
| JPS5371068A (en) | 1978-06-24 |
| GB1572309A (en) | 1980-07-30 |
| IE46001B1 (en) | 1983-01-26 |
| FR2381756A2 (en) | 1978-09-22 |
| IE46001L (en) | 1978-06-03 |
| AT361917B (en) | 1981-04-10 |
| ATA866177A (en) | 1980-09-15 |
| ES464533A2 (en) | 1979-10-16 |
| DE2654797A1 (en) | 1978-06-08 |
| NL7713083A (en) | 1978-06-06 |
| BE861500R (en) | 1978-06-05 |
| DK538777A (en) | 1978-06-04 |
| LU78614A1 (en) | 1978-07-14 |
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