US4518776A
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Process for producing sulfonylureas
Assignee: Novartis Corp
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Filing: 1983-07-08
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Granted: 1985-05-21
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Expires: 2003-07-08
Abstract
Abstract There is described a process for producing sulfonylureas of the formula ##STR1## wherein G is an unsubstituted or substituted furanyl, thienyl, pyrrolyl, pyridinyl or phenyl radical, X is alkyl, haloalkyl, alkoxy, alkylthio, halogen, haloalkoxy, alkylamino or dialkylamino, Y is alkyl, alkoxy or haloalkoxy, Z is a nitrogen atom or the methyne group --CH═. This novel process comprises reacting a sulfonamide of the formula G--SO.sub.2 --NH.sub.2, in the presence of a base, with a chloroformic acid ester of the formula Cl--CO--Q--T, or a sulfonyl chloride of the formula G--SO.sub.2 Cl, in the presence of a base, with a urethane of the formula H.sub.2 N--CO--Q--T; and converting the formed carbamate of the formula G--SO.sub.2 --NH--CO--Q--T by reaction with an amine of the formula ##STR2## into the sulfonylurea of the above formula. There is also described novel sulfonylcarbamates of the above formula as intermediates.
Inventors
- 👤 Willy Meyer
- 👤 Werner Fory
- 👤 Werner Topfl
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 09:06
CPC Classifications
C; C07; C07D; C07D521/00; C07D333/00; C07D333/02; C07D333/04; C07D333/26; C07D333/38
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
505 words
A process for producing a sulfonylurea of the general formula I ##STR9## wherein Z is an --N═ or --CH═ radical, G is a radical of the formula ##STR10## X is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, halogen, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylamino or di-C 1 -C 4 -alkylamino, Y is C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, A is oxygen, sulfur, --NR 5 -- or --C═N--, where R 5 is hydrogen, C 1 -C 4 -alkyl or --CO--C 1 -C 4 alkyl, R 1 is hydrogen, C 1 -C 4 -alkyl, halogen, nitro, cyano, --NH 2 , --S(O) n --C 1 -C 4 -alkyl, --SO 2 --C 1 -C 4 -alkoxy, --SO 2 --di-C 1 -C 4 -alkylamino, --CHO, --CONH 2 , --D--C 3 -C 5 -alkynyl, --CO--D--C 3 -C 5 -alkynyl, --D--C 1 -C 4 -alkyl, --D--C 3 -C 5 -alkenyl, --CO--C 1 -C 4 -alkyl, --CO--D--C 1 -C 4 -alkyl or --CO--D--C 3 -C 5 -alkenyl, n being one or two, and D being an oxygen, sulfur, --NH-- or --N(C 1 -C 4 -alkyl)-bridge, R 2 is hydrogen, halogen, CF 3 , NO 2 , C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy, R 3 is hydrogen, fluorine or chlorine, and R 4 is halogen, C 1 -C 4 -alkyl, nitro, cyano, --NH 2 , --S(O) n --C 1 -C 4 -alkyl, --SO 2 --C 1 -C 4 -alkoxy, --SO 2 -di-C 1 -C 4 -alkylamino, --CHO, --CONH 2 , --D--C 3 -C 5 -alkynyl, --CO--D--C 3 -C 5 -alkynyl, trifluoromethyl, or C 1 -C 4 -alkoxy substituted by cyano, halogen, C 1 -C 4 -alkoxy or C 1 -C 4 -alkylthio, or is --D--C 1 -C 4 -alkyl, --D--C 3 -C 5 -alkenyl, --CO--C 1 -C 4 -alkyl, 1,2-dichlorovinyloxy, --CO--D--C 1 -C 4 -alkyl or --CO--D--C 3 -C 5 -alkenyl, n being one or two, and D being an oxygen, sulfur, --NH-- or --N(C 1 -C 4 -alkyl)-bridge, which process comprises reacting a sulfonamide of the formula II G--SO.sub.2 --NH.sub.2 (II), in the presence of a base, with a chloroformic acid ester of the formula III Cl--CO--Q--T (III), or a sulfonyl chloride of the formula IV G--SO.sub.2 --Cl (IV), in the presence of a base, with a urethane of the formula V H.sub.2 N--CO--Q--T (V), wherein G has the meaning defined under the formula I, Q is oxygen or sulfur, and T is C 1 -C 4 -alkyl, benzyl, C 1 -C 4 -haloalkyl, C 1 -C 3 -cyanoalkyl, C 2 -C 5 -alkenyl, or alkoxyalkyl or alkylthioalkyl having a total of at most 5 carbon atoms; and converting the formed carbamate of the formula VI G--SO.sub.2 --NH--CO--Q--T (VI) by reaction with an amine of the formula VII ##STR11## wherein G, Q, T, X, Y and Z have the meanings defined in the foregoing, into the sulfonylurea of the formula I.
Claim 2
Dependent Claim
505 words
A process for producing a sulfonylurea of the general formula I ##STR9## wherein Z is an --N═ or --CH═ radical, G is a radical of the formula ##STR10## X is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, halogen, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylamino or di-C 1 -C 4 -alkylamino, Y is C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, A is oxygen, sulfur, --NR 5 -- or --C═N--, where R 5 is hydrogen, C 1 -C 4 -alkyl or --CO--C 1 -C 4 alkyl, R 1 is hydrogen, C 1 -C 4 -alkyl, halogen, nitro, cyano, --NH 2 , --S(O) n --C 1 -C 4 -alkyl, --SO 2 --C 1 -C 4 -alkoxy, --SO 2 --di-C 1 -C 4 -alkylamino, --CHO, --CONH 2 , --D--C 3 -C 5 -alkynyl, --CO--D--C 3 -C 5 -alkynyl, --D--C 1 -C 4 -alkyl, --D--C 3 -C 5 -alkenyl, --CO--C 1 -C 4 -alkyl, --CO--D--C 1 -C 4 -alkyl or --CO--D--C 3 -C 5 -alkenyl, n being one or two, and D being an oxygen, sulfur, --NH-- or --N(C 1 -C 4 -alkyl)-bridge, R 2 is hydrogen, halogen, CF 3 , NO 2 , C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy, R 3 is hydrogen, fluorine or chlorine, and R 4 is halogen, C 1 -C 4 -alkyl, nitro, cyano, --NH 2 , --S(O) n --C 1 -C 4 -alkyl, --SO 2 --C 1 -C 4 -alkoxy, --SO 2 -di-C 1 -C 4 -alkylamino, --CHO, --CONH 2 , --D--C 3 -C 5 -alkynyl, --CO--D--C 3 -C 5 -alkynyl, trifluoromethyl, or C 1 -C 4 -alkoxy substituted by cyano, halogen, C 1 -C 4 -alkoxy or C 1 -C 4 -alkylthio, or is --D--C 1 -C 4 -alkyl, --D--C 3 -C 5 -alkenyl, --CO--C 1 -C 4 -alkyl, 1,2-dichlorovinyloxy, --CO--D--C 1 -C 4 -alkyl or --CO--D--C 3 -C 5 -alkenyl, n being one or two, and D being an oxygen, sulfur, --NH-- or --N(C 1 -C 4 -alkyl)-bridge, which process comprises reacting a sulfonamide of the formula II G--SO.sub.2 --NH.sub.2 (II), in the presence of a base, with a chloroformic acid ester of the formula III Cl--CO--Q--T (III), or a sulfonyl chloride of the formula IV G--SO.sub.2 --Cl (IV), in the presence of a base, with a urethane of the formula V H.sub.2 N--CO--Q--T (V), wherein G has the meaning defined under the formula I, Q is oxygen or sulfur, and T is C 1 -C 4 -alkyl, benzyl, C 1 -C 4 -haloalkyl, C 1 -C 3 -cyanoalkyl, C 2 -C 5 -alkenyl, or alkoxyalkyl or alkylthioalkyl having a total of at most 5 carbon atoms; and converting the formed carbamate of the formula VI G--SO.sub.2 --NH--CO--Q--T (VI) by reaction with an amine of the formula VII ##STR11## wherein G, Q, T, X, Y and Z have the meanings defined in the foregoing, into the sulfonylurea of the formula I.
Claim 3
Dependent Claim
31 words
A process according to claim 1, wherein the reaction of the carbamate of the formula VI with the amine of the formula VII is performed at a temperature of 50°-220° C.
Claim 4
Dependent Claim
15 words
A process according to claim 2, wherein the reaction temperature is 80° to 160° C.
Claim 5
Dependent Claim
29 words
A process according to claim 1, wherein the reaction of the carbamate of the formula VI with the amine of the formula VII is performed in an inert solvent.
Claim 6
Dependent Claim
22 words
A process according to claim 4, wherein the solvent is selected from the group comprising: hydrocarbons, ethers, nitriles, ketones or dimethyl sulfoxide.
Claim 7
Dependent Claim
48 words
A process according to claim 1, wherein the reaction of the sulfonamide of the formula II with the chloroformic acid ester of the formula III, or of the sulfonyl chloride of the formula IV with the urethane of the formula V is performed at 0° to 140° C.
Claim 8
Dependent Claim
15 words
A process according to claim 6, wherein the reaction temperature is 10° to 80° C.
Claim 9
Dependent Claim
60 words
A process according to claim 1, wherein the reaction of the sulfonamide of the formula II with the chloroformic acid ester of the formula III, or of the sulfonyl chloride of the formula IV with the urethane of the formula V is performed in the presence of a base from the group comprising: carbonates, hydrogen carbonates, oxides and tertiary amines.
Claim 10
Dependent Claim
47 words
A process according to claim 1, wherein the reaction of the sulfonamide of the formula II with the chloroformic acid ester of the formula III, or of the sulfonyl chloride of the formula IV with the urethane of the formula V is performed in an inert solvent.
Claim 11
Dependent Claim
22 words
A process according to claim 9, wherein the solvent is selected from the group comprising: hydrocarbons, ethers, nitriles, ketones or dimethyl sulfoxide.
Claim 12
Dependent Claim
97 words
A process according to claim 1, which process comprises reacting a sulfonamide of the formula II with a chloroformic acid ester of the formula III, or reacting a sulfonyl chloride of the formula IV, in the presence of a base and in an inert solvent at 10° to 80° C., with a urethane of the formula V, and heating the resulting carbamate of the formula VI together with an amine of the formula VII, in an inert solvent at 80° to 160° C., until the cleavage reaction of alcohol or mercaptan has finished; and isolating the product.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-05-20 | 1988-11-19 | 1989-05-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-05-20 | 1992-11-19 | 1993-05-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-05-20 | 1996-11-19 | 1997-05-21 | $7700.00 | Window Closed / Lapsed |