Patent GB-1173312-A (GB)
Title: Heterocyclic Compounds
Inventor: HJORTKJAER JES
IPC: C07D307/88
Filed: 1966-03-17
Abstract: 1,173,312. Phthalane derivatives. KEFALAS A.S. 7 March, 1967 [17 March, 1966], No. 11870/66. Heading C2C. Novel compounds of Formula I wherein R<SP>1</SP> and R<SP>2</SP> each represents hydrogen, a lower-alkyl group or phenyl, R<SP>3</SP> and R<SP>4</SP> when taken together with the nitrogen atom represent an amino group, a mono-lower-alkylamino group, a di-lower-alkylamino group, a benzyllower-alkylamino group or the radical of a heterocyclic amine having a saturated fivemembered or six-membered ring, " alkylene " represents a straight or branched alkylene chain having from 2-6 carbon atoms, at least two carbon atoms being in the chain directly connecting the ring carbon atom with the nitrogen atom, X represents hydrogen, halogen, a loweralkyl group, a lower-alkyloxy group or a trinalomethyl group, and R<SP>5</SP> represents one of the groups -CN, -COOH, -CO.NH R<SP>6</SP> or -COOR<SP>7</SP>, wherein R<SP>6</SP> represents hydrogen, a lower-alkyl group or phenyl and R<SP>7</SP> represents a lower-alkyl group and acid addition salts thereof with pharmaceutically acceptable acids are prepared by (a) reacting a compound of the Formula II wherein alkylene has 3-6 carbon atoms with an alkali metal cyanide in the presence of a mineral acid or an organic acid, or (b) reacting a compound of the Formula III wherein X, R<SP>1</SP> and R<SP>2</SP> are as defined above with a compound of the formula hal.alkylene.NR<SP>3</SP>R<SP>4</SP> wherein R<SP>3</SP> and R<SP>4</SP> and " alkylene " are as defined above, and " hal " represents a halogen atom, in the presence of a condensing agent and isolating the cyano-compound formed as the free base or in the form of an acid addition salt with a pharmaceutically acceptable acid, or (c) converting the -CN group to either -COOH or -CO.NH 2  in well-known manner and if desired esterifying the -COOH group to -COOR<SP>7</SP>, or (d) converting the ester group -COOR<SP>7</SP> to -CO.NH.R<SP>6</SP> in conventional manner, or (e) for compounds of Formula I above wherein R<SP>3</SP> is H, R<SP>4</SP> is a lower-alkyl group and R<SP>5</SP> is -COOH, or -CO.NH.R<SP>6</SP>, wherein R<SP>6</SP> is as previously defined, by reacting a compound of Formula I, wherein R<SP>3</SP> and R<SP>4</SP> each is a lower-alkyl group or R<SP>4</SP> is a loweralkyl group and R<SP>3</SP> is a benzyl group with a chloroformic acid ester of the formula Cl COO R<SP>8</SP>, wherein R<SP>8</SP> represents a lower-alkyl group or a benzyl group, hydrolysing the resulting compound of the formula and in all cases isolating the compounds as the free amine or as an acid additive salt (in the above lower denotes a group containing up to 8 carbon atoms). Nitriles of Formula III above are prepared by reaction of an alkalimetal cyanide and the corresponding 3-hydroxy-phthalane. 3-Aminoalkyl-phthalan-3-ols of Formula II above are prepared by reacting a ketone of formula and a Grignard reagent formed from the appropriate aminoalkyl halide. Pharmaceutical composition in conventional forms for oral, rectal or paranteral administration comprise an above novel compound or a pharmaceutically acceptable salt thereof and a carrier or diluent therefor.