GB1433151A — Benzo-ij-quinolizines

USPTO Abstract

1433151 Benzo[ij]quinolizines ALLEN & HANBURYS Ltd 19 March 1974 [5 April 1973] 16279/73 Heading C2C [Also in Division A5] Novel benzo[ij]quinolizines of the formula wherein R 1 is H, alkyl or OR 3 , where R 3 is H, acyl or alkenyl or an alkyl group optionally substituted by amino, dialkylamino, alkylarylamino, aryl, aryloxy, acyloxy, alkoxy, hydroxy or tetrahydropyranyloxy, and up to 3 groups R 1 , which may be the same or different are present; and R<SP>2</SP> is H or alkyl, and pharmaceutically acceptable salts thereof are prepared by reacting the appropriate 6,7-dihydro-1-oxo- 1H,5H - benzo[ij]quinolizine - 2 - carboxylic acids or reactive derivatives thereof with 5- amino - 1H - tetrazole. Compounds of the formula above in which R 1 is OH may be obtained by the hydrogenolysis of the corresponding compounds in which R 1 is benzyloxy, those in which R 1 is trifluoroacetoxy by treating the corresponding compound in which R 1 is 2- tetrahydropyranyloxy with trifluoroacetic acid, and those in which R 1 is hydroxyalkoxy by hydrolysing the corresponding compounds in which R 1 is trifluoroacetoxy. 9 - Ethoxy (or 9 - (2 - hydroxyethoxy)-, or 9 - (2 - ethoxyethoxy)-, or 9 - (2 - tetrahydropyran - 2<SP>1</SP> - yloxyethoxy)-, or 9 - isopropoxy -)- 6,7 - dihydro - 1 - oxo - 1H,5H - benzo[ij]- quinolizine-2-carboxylic acid is obtained by reacting diethyl sulphate (or 2-bromoethanol or 2-ethoxyethyl bromide or 2-tetrahydropyran-21- yloxyethyl bromide or isopropyl bromide) with 9 - hydroxy - 6,7 - dihydro - 1 - oxo - 1H,5H - benzo[ij]quinolizine 2 - carboxylic acid resulting from the demethylation of the corresponding 9-methoxy compound. 9 - Allyloxy - 6,7 - dihydro - 1 - oxo - 1H,5H- benzo[ij]quinolizine - 2 - carboxylic acid is obtained by hydrolysing the corresponding allyl ester, which is prepared by reacting allyl bromide with 9-hydroxy-6,7 -dihydro- 1-oxo-1H,- 5H-benzo[ij]quinolizine-2-carboxylic acid. 9- Benzyloxy - 6,7 - dihydro - 1 - oxo - 1H,5H- benzo[ij]quinolizine-2-carboxylic acid and its benzyl ester are obtained in a similar manner. 6,7 - Dihydro - 9 - (2 - dimethylaminoethoxy)- 1 - oxo - 1H,5H - benzo[ij]quinolizine - 2 - carboxylic acid hydrochloride and 9-[2-(N-benzyl-N- methylamino)ethoxy]- 6,7 - dihydro - 1 - oxo- 1H,5H - benzo[ij]quinolizine - 2 - carboxylic acid hydrochloride, monohydrate are obtained by reacting 6,7-dihydro-9-hydroxy-1-oxo-1H,5H- benzo[ij]quinolizine - 2 - carboxylic acid with 2-dimethylaminoethyl chloride hydrochloride and N-benzyl-N-methylaminoethyl bromide respectively and hydrolysing the esters thus obtained. 6,7 - Dihydro - 9 - isopropyl - 1 - oxo - 1H,5H- benzo[ij]quinolizine - 2 - carboxylic acid is prepared by hydrolysing the corresponding ethyl ester, obtained by cyclizing diethyl [(1,2,3,4- tetrahydro - 6 - isopropylquinol - 1 - yl)-methylene]malonate resulting from the reacting between diethyl ethoxymethylenemalonate and 1,2,3,4 - tetrahydro - 6 - isopropylquinoline, which is made by hydrogenating 6-isopropylquinoline.