Patent GB-1054095-A (GB)
IPC: C07D221/20
Filed: 1965-06-14
Abstract: 1,054,095. Isoquinoline derivatives. F. HOFFMANN-LA ROCHE & CO. A.G. June 14, 1965 [June 16, 1964], No. 25070/65. Heading C2C. New 7-oxo-cyclopent[i,j]-isoquinoline derivatives of general formula wherein R 1  and R 2  represent hydrogen or an alkyl or alkanoyl group of up to seven carbon atoms, or together represent the methylene group, and R 3  represents hydrogen or an alkyl, alkenyl group of up to seven carbon atoms, aralkyl or cycloalkyl alkyl group or the acyl group derived from a lower aliphatic or aromatic carboxylic acid, and acid addition salts, quaternary salts and quaternary bases thereof, are prepared by cyclizing a tetrahydroisoquinoline compound of general formula wherein R 1 , R 2  and R 3  have the above significance and X represents carboxyl, halocarbonyl, alkoxycarbonyl, aryloxycarbonyl or arylkoxycarbonyl group, or an acid addition salt, a quarternary salt or a quaternary base thereof. for example using polyphosphoric, concentrated phosphoric, hydrofluoric, or sulphuric acid at elevated temperatures in the case where X represents a carbonyl group, and by using a Friedel-Crafts type catalyst such as an aluminium trihalide, boron trifluoride or zinc chloride in the case where X represents halo-carbonyl and, when required, converting the product into an acid-addition, quaternary salt or quaternary base thereof. If required, R<SP>1</SP> and/or R<SP>2</SP> may be modified in that an alkyl group may be replaced by hydrogen, for example by reaction with hydrobromic acid, and hydrogen values may be converted into alkanoyl values, for example by reaction with an acid anhydride. In addition, when R<SP>3</SP> is hydrogen, the hydrogen may be replaced by any other value for R<SP>3</SP>, for example by reaction with the appropriate organo-halide or anhydride to introduce a benzyl, allyl, cyclopropylmethyl, acetyl or 4-chloro-benzoyl group at the 1-position. Epoxy compounds of the general formula wherein R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> have the above significance and R<SP>4</SP> is hydrogen, alkoxycarbonyl, aryloxycarbonyl or aralkoxycarbonyl, are prepared by reacting the compounds of the first general formula above with a trimethylsulphonium- or trimethylsulphoxonium halide in the presence of a base, a halo-acetic acid alkyl, aryl or aralkyl ester in the presence of a base, or diazomethane. Compounds of the general formula wherein R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> have the above significance and R<SP>5</SP> is alkyl, are prepared by reacting the compounds of the first general formula above with a triphenylphosphonium compound having a cation of the formula wherein R<SP>5</SP> has the above significance. 7.Formyl compounds of the general formula wherein R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> have the above significance, are prepared by treating the above epoxy compounds with a Lewis acid, a strong mineral acid or trifluoro-acetic acid when R<SP>4</SP> is hydrogen, or with a strong base when R<SP>4</SP> is other than hydrogen, or by treating the compounds of the previous general formula with a strong mineral acid or a Lewis acid. 1 - Carboxymethyl - 2 - methyl - 6,7 - dimethoxy - 1,2,3,4 - tetrahydro - isoquinoline hydrochloride is obtained by reacting 1-ethoxycarbonylmethyl - 6,7 - dimethoxy 1,2,3,4-tetrahydroisoquinoline with formic acid and formaldehyde and treating the reaction product with aqueous hydrochloric acid. 1 - Carboxymethyl - 6,7 - dimethoxy - 1,2,3,4- tetrahydro-isoquinoline hydrochloride is obtained by steam distilling the corresponding 1-methoxycarbonylmethyl compound in the presence of hydrochloric acid. Pharmaceutical compositions having blood pressure lowering activity and also analgesic, antiphlogistic, µdema-inhibiting and antipyretic action, and which can be administered enterally, or parenterally in the form of tablets, dragees, suppositories, or capsules, or as solutions, suspensions, or emulsions, contain a compound of the first general formula above, as the active ingredient.