US4212804A
Expired / Lapsed
US
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Process for the preparation of optionally substituted 2,3-indolinediones
Assignee: Sandoz Inc
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Filing: 1978-12-04
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Granted: 1980-07-15
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Expires: 1998-12-04
Abstract
Abstract An improved process for the preparation of optionally substituted 2,3-indolinediones which are useful as intermediates in the preparation of compounds having pharmacological activity which comprises reacting a 3,1-benzoxazine with an alkali or alkaline earth metal cyanide or a tetra-(C 1-4 ) alkylammonium cyanide to obtain a 2-imino-3-indolinone, which is then subjected to hydrolysis.
Inventors
- 👤 Gary M. Coppola
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 05:59
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/04; C07D209/30; C07D209/32; C07D209/38; C07D209/40
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
198 words
A process for the preparation of a 2,3-indolinedione of the formula: ##STR6## wherein R is hydrogen; C 1-4 alkyl; C 3-6 alkenyl; C 3-6 alkynyl; unsubstituted phenyl; phenyl substituted by one or two substituents independently selected from C 1-4 alkyl, C 1-4 alkoxy, fluoro, chloro and bromo; unsubstituted benzyl; or benzyl substituted on the benzene ring by one or two substituents independently selected from C 1-4 alkyl, C 1-4 alkoxy, fluoro, chloro and bromo; X is fluoro; chloro; bromo; C 1-4 alkyl; C 1-4 alkoxy; or nitro; or two adjacent X's together may also form methylenedioxy; and n is 0 or an integer 1 or 2, the two X's being the same or different when n is 2, which comprises reacting a 3,1-benzoxazine of the formula, ##STR7## wherein R, X and n are as defined above, with an alkali or alkaline earth metal cyanide or a tetra-(C 1-4 ) alkylammonium cyanide in a molar ratio of cyanide compound to benzoxozine compound of about at least 1:1, to decarboxylate said 3,1-benzoxazine and obtain a 2-imino-3-indolinone of the formula, ##STR8## wherein R, X and n are as defined above, said 2-imino-3-indolinone then being subjected to hydrolysis to obtain said 2,3-indolinedione.
Claim 2
Dependent Claim
198 words
A process for the preparation of a 2,3-indolinedione of the formula: ##STR6## wherein R is hydrogen; C 1-4 alkyl; C 3-6 alkenyl; C 3-6 alkynyl; unsubstituted phenyl; phenyl substituted by one or two substituents independently selected from C 1-4 alkyl, C 1-4 alkoxy, fluoro, chloro and bromo; unsubstituted benzyl; or benzyl substituted on the benzene ring by one or two substituents independently selected from C 1-4 alkyl, C 1-4 alkoxy, fluoro, chloro and bromo; X is fluoro; chloro; bromo; C 1-4 alkyl; C 1-4 alkoxy; or nitro; or two adjacent X's together may also form methylenedioxy; and n is 0 or an integer 1 or 2, the two X's being the same or different when n is 2, which comprises reacting a 3,1-benzoxazine of the formula, ##STR7## wherein R, X and n are as defined above, with an alkali or alkaline earth metal cyanide or a tetra-(C 1-4 ) alkylammonium cyanide in a molar ratio of cyanide compound to benzoxozine compound of about at least 1:1, to decarboxylate said 3,1-benzoxazine and obtain a 2-imino-3-indolinone of the formula, ##STR8## wherein R, X and n are as defined above, said 2-imino-3-indolinone then being subjected to hydrolysis to obtain said 2,3-indolinedione.
Claim 3
Dependent Claim
27 words
The process according to claim 1 in which the 3,1-benzoxazine is reacted with an alkali metal cyanide at a temperature of from about 80° to 140° C.
Claim 4
Dependent Claim
26 words
The process according to claim 2 wherein the 3,1-benzoxazine is reacted with an alkali metal cyanide at a temperature of from about 90° to 120° C.
Claim 5
Dependent Claim
14 words
The process according to claim 2 wherein the alkali metal cyanide is potassium cyanide.
Claim 6
Dependent Claim
29 words
The process according to claim 1 in which the 3,1-benzoxazine is reacted with a tetra-(C 1-4 ) alkylammonium cyanide at a temperature of from about 10° to 80° C.
Claim 7
Dependent Claim
28 words
The process according to claim 5 wherein the 3,1-benzoxazine is reacted with a tetra-(C 1-4 ) alkylammonium cyanide at a temperature of from about 30° to 50° C.
Claim 8
Dependent Claim
16 words
The process according to claim 5 wherein the tetra-(C 1-4 ) alkylammonium cyanide is tetraethylammonium cyanide.
Claim 9
Dependent Claim
57 words
The process according to claim 1 in which the 3,1-benzoxazine is reacted with potassium cyanide in an equimolar ratio or in the presence of a slight excess of potassium cyanide at a temperature of 100° C., to decarboxylate said 3,1-benzoxazine and obtain a 2-imino-3-indolinone, said 2-imino-3-indolinone then being hydrolyzed under mild, acidic conditions to obtain a 2,3-indolinedione.
Claim 10
Dependent Claim
57 words
The process according to claim 1 in which the 3,1-benzoxazine is reacted with tetraethylammonium cyanide in an equimolar ratio or in the presence of a slight excess of tetraethylammonium cyanide at a temperature of 40° C., to decarboxylate said 3,1-benzoxazine and obtain a 2-imino-3-indolinone, said 2-imino-3-indolinone then being hydrolyzed under mild, acidic conditions to obtain a 2,3-indolinedione.
References Cited (Backward Citations)
No citation records indexed.
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