American Home Products Corporation

Charles J Guinosso

John H Sellstedt

Albert J Begany

Dieter H Klaubert

David A Shriver

Daniel M Teller

Disclosed herein is a process for preparing indoline-2-carboxylic acids from the corresponding indole-2-carboxylic acid or ester in which the indole-2-carboxylic acid or ester is first reduced to the indoline-2-carboxylic acid ester tin complex using stannous chloride and dry hydrogen chloride gas in a lower alkanol solvent at atmospheric pressures; and the resulting tin complex, dissolved in a lower alkanol, is converted directly to the free indoline-2-carboxylic acid by treatment with aqueous potassium or sodium hydroxide. The aqueous hydroxide treatment may take place in situ or after first isolating the intermediate indoline-2-carboxylic acid ester tin complex.

Preparation of indoline-2-carboxylic acid via the intermediate

Variously substituted oxanilic acid esters possessing anti-secretory activity are useful anti-ulcer agents.

Antisecretory oxamic acid esters

Anti-allergic agents of aromatic oxamic acid derivation present the following formula: ##STR1## in which A is a member selected from the group consisting of .alpha.-naphthyl, .beta.-napthtyl, phenyl, 2,6-di-chlorophenyl, and substituted phenyl moieties containing from one to three substituents in any of the 2,3,4 and 5 positions of the phenyl ring, independently selected from the group consisting of lower alkyl, lower alkylthio, lower alkylsulfinyl, lower alkoxy, hydroxy (lower)alkoxy, 2-(oxalyloxy) ethoxy, benzyloxy, N-mono- and di-lower alkylamino(lower)alkoxy, halo, sulfamyl, polyhalo(lower)alkyl, carbamyl, N-lower alkylcarbamyl, nitro, mono and di lower alkylamino, carboxy, lower alkylcarbonyl, carb(lower)alkoxy, phenoxy(lower)alkoxy, and oxalamidophenoxy radicals; and pharmaceutically acceptable salts thereof.

Oxamic acid derivatives

Anti-allergic agents of aromatic and heterocyclic oxamic acid derivation present the following formula: ##STR1## in which A is a member selected from the group consisting of 2-thiazolyl, 2-pyridyl, 2-pyridyl-N-oxide, 6-(lower)alkyl-2-pyridyl, 3-cyano-2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 2-pyrazinyl, .alpha.-naphthyl, .beta.-naphthyl, phenyl, 2,6-di-chlorophenyl, and substituted phenyl moieties containing from one to three substituents in any of the 2,3,4 and 5 positions of the phenyl ring, independently selected from the group consisting of lower alkyl, lower alkylthio, lower alkylsulfinyl, lower alkoxy, hydroxy(lower)alkoxy, 2-(lower alkoxy oxalyloxy) ethoxy, benzyloxy, N-mono-and di-lower alkylamino(lower)alkoxy, halo, sulfamyl, polyhalo(lower)alkyl, carbamyl, N-lower alkylcarbamyl, nitro, mono-and di-lower alkylamino, phenylazo, carboxy, lower alkylcarbonyl, cyano, carb(lower)alkoxy, phenoxy(lower)alkoxy, lower alkoxyoxalamido and lower alkoxyoxalamidophenoxy radicals;

Anti-allergic agents of aromatic oxamic acid derivation present the following formula: ##STR1## in which A is a member selected from the group consisting of .alpha.-naphthyl, .beta.-naphthyl, phenyl, 2,6-di-chlorophenyl, and substituted phenyl moieties containing from one to three substituents in any of the 2,3,4 and 5 positions of the phenyl ring, independently selected from the group consisting of lower alkyl, lower alkylthio, lower alkylsulfinyl, lower alkoxy, hydroxy (lower)alkoxy, 2-(oxalyloxy) ethoxy, benzyloxy, N-mono- and di-lower alkylamino(lower)alkoxy, halo, sulfamyl, polyhalo(lower)alkyl, carbamyl, N-lower alkylcarbamyl, nitro, mono and di lower alkylamino, carboxy, lower alkylcarbonyl, carb(lower)alkoxy, phenoxy(lower)alkoxy, and oxalamidophenoxy radicals; And pharmaceutically acceptable salts thereof.

Variously substituted oxanilic acid esters possessing anti-secretary activity are useful anti-ulcer agents.

Anti-allergic agents of N-(2-pyrazinyl) 1H- (or 2H) tetrazole-5-carboxamide derivation present the following formulae: ##STR1## in which R.sup.1 is hydrogen, lower alkylamino, di(lower)alkylamino, cyano, halo, lower alkyl or halo; and

N-(2-pyrazinyl) 1H- (or 2H) tetrazole-5-carboxamide derivatives for the

Anti-allergic agents of N-(2-thiazolyl)-1H-(or 2H) tetrazole-5-carboxamide derivation present the following formulae: ##STR1## in which R is hydrogen, lower alkyl, lower alkoxy, --CN, (lower)alkyl amino, di(lower) alkylamino, polyhalo(lower)alkyl, halo and carbamoyl; Or a pharmaceutically acceptable salt thereof.

N-(2-thiazolyl)-tetrazole-5-carboxamide derivatives for the prevention

Anti-allergic agents of N-(pyridyl)-1H-(or 2H) Tetrazole-5-carboxamide derivation present the following formulae: ##STR1## in which R is --H or lower alkyl;

N-(Pyridyl)-1H-(or 2H) tetrazole-5-carboxamide derivatives for the

Anti-allergic agents of N-(2-pyrimidinyl)-1H-(or 2H)tetrazole-5-carboxamide derivation present the following formulae: ##STR1## in which R.sup.1 and R.sup.2 are independently hydrogen, cyano, lower alkyl, carbamyl, halo, (lower) alkylamino or di(lower)alkylamino, or a pharmaceutically acceptable salt thereof.

N-(2-pyrimidinyl)1H-(or 2H)tetrazole-5-carboxamide derivatives for the

Anti-allergic agents of N-(pyridyl)-oxamic acid derivation present the following formulae: ##STR1## in which R is --H or lower alkyl; R.sup.2 is --H, lower alkoxy, lower alkyl, halo or polyhalo(lower) alkyl; Or a pharmaceutically acceptable salt thereof.

N-(pyridyl) oxamic acid derivatives

The 2-cyano-3-or 4-(substituted amino) oxanilic acid derivatives of the formula: ##STR1## in which the group ##STR2## appears in the designated 3- or 4- position and R is --H; an alkali metal; .sup.+ NH.sub.4 ; alkyl of 1 to 6 carbon atoms, inclusive; aralkyl of 7 or 8 carbon atoms; or cycloalkyl of 5 or 6 carbon atoms;

2-Cyano-3- or 4-(substituted amino)oxanilic acid derivatives

Anti-allergic agents of aromatic oxamic acid derivation present the following formula: ##STR1## in which A is a member selected from the group consisting of .alpha.-naphthyl, .beta.-naphthyl, phenyl, 2,6-dichlorophenyl, and substituted phenyl moieties containing from one to three substituents in any of the 2,3,4 and 5 positions of the phenyl ring, independently selected from the group consisting of lower alkyl, lower alkylthio, lower alkylsulfinyl, lower alkoxy, hydroxy (lower)alkoxy, 2-(oxalyloxy) ethoxy, benzyloxy, N-mono- and di-lower alkylamino(lower)alkoxy, halo, sulfamyl, polyhalo(lower)alkyl, carbamyl, N-lower alkylcarbamyl, nitro, mono and di lower alkylamino, carboxy, lower alkylcarbonyl, carb(lower)alkoxy, phenoxy(lower)alkoxy, and oxalamidophenoxy radicals; And pharmaceutically acceptable salts thereof.

Oxamic acid derivatives for the prevention of immediate type

The 2-cyano-3-or 4-(substituted amino)oxanilic acid derivatives of the formula: ##STR1## in which the group ##STR2## appears in the designated 3- or 4- position and R is -H; an alkali metal; .sup.+ NH.sub.4 ; alkyl of 1 to 6 carbon atoms, inclusive; aralkyl of 7 or 8 carbon atoms; or cycloalkyl of 5 or 6 carbon atoms;

2-Cyano-3-or 4-(substituted amino)oxanilic acid derivatives

Anti-allergic agents of aromatic and heterocyclic oxamic acid derivation present the following formula: ##STR1## in which A is a member selected from the group consisting of 2-thiazolyl, 2-pyridyl, 2-pyridyl-N-oxide, 6-(lower)alkyl-2-pyridyl, 3-cyano-2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 2-pyrazinyl, .alpha.-naphthyl, .beta.-naphthyl, phenyl, 2,6-dichlorophenyl, and substituted phenyl moieties containing from one to three substituents in any of the 2,3,4 and 5 positions of the phenyl ring, independently selected from the group consisting of lower alkyl, lower alkylthio, lower alkylsulfinyl, lower alkoxy, hydroxy(lower)-alkoxy, 2-(lower alkoxy oxalyloxy) ethoxy, benzyloxy, N-mono- and di-lower alkylamino(lower)-alkoxy, halo, sulfamyl, polyhalo(lower)alkyl, carbamyl, N-lower alkylcarbamyl, nitro, mono- and di-lower alkylamino, phenylazo, carboxy, lower alkylcarbonyl, cyano, carb(lower)alkoxy, phenoxy(lower)alkoxy, lower alkoxyoxalamido and lower alkoxyoxalamidophenoxy radicals; B, when taken alone, is a member selected from the group consisting of --OH, lower alkoxy, --NH.sub.2, --NHOH, cyclohexyloxy and phenoxy; and

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King of Prussia, PA, United States of America

Charles J Guinosso