Patent GB-1164192-A (GB)
Title: Tetrahydroisoquinolines and process for preparing them
IPC: C07D217/04
Filed: 1967-05-05
Abstract: 1,164,192. 4-Phenyl-tetrahydroquinoline derivatives. FARBWERKE HOECHST A.G. 5 May, 1967 [5 May, 1966; 12 Aug., 1966; 15 April, 1967 (2)], No. 21016/67. Heading C2C. Novel compounds of the Formula (I) wherein R is H or alkyl, R 1  is H, acyl of a saturated or unsaturated C 2-6  aliphatic, aromatic or araliphatic carboxylic acid, C 1-5  alkyl, C 7-10  aralkyl; R 2  and R 2 <SP>1</SP> may be the same or different and each represent H, halogen, OH, CF 3 , C 1-5  alkyl or alkoxy, C 7-10  aralkoxy, or R 2  and R 2 <SP>1</SP> together represent C 1-2  alkylenedioxy; R 3  and R 4  are identical or different and represent H, C 1-5  alkyl, phenyl, or C 7-10  aralkyl, and R 5  is H, halogen, OH, CF 3 , NO 2 , C 1-4  alkyl or alkoxy, or C 7-10  aralkoxy; or a salt thereof, are obtained by (a) effecting ring closure in a compound of the Formula (II) where X is -CHOH, optionally esterified by a sulphonic or carboxylic acid, or a CH-halogen group, by treating it with an acid condensing agent, or (b) treating a compound of the Formula I above (but where R 1  is H and R 4  is not H) with an agent for introducing the acyl radical of a saturated or unsaturated aliphatic carboxylic acid of up to 6 carbon atoms, an aromatic or araliphatic carboxylic acid, or (c) reducing by means of a complex metal hydride, a compound of general Formula IV in which R, R 1 , R 2 , R 2 1, R 4  and R 5  have the meanings given above and R 4  may also represent hydrogen, and, if desired, treating with an alkylating agent a compound of the general Formula I, in which R 1  and/or R 4  represent a hydrogen atom, or by separating in known manner benzyl radicals from a compound of the general Formula I, in which the R 1  and/or R 4  represents benzyl radicals, and/or treating with an ether splitting agent a compound of the general Formula I, in which R 2 , R 2 <SP>1</SP> and/or R 5  represent alkoxy or aralkoxy groups, and, if desired, converting the salt obtained into the free base or converting the free base obtained into a physiologically tolerable salt by a treatment with an acid. The following intermediates are also described:- (a) N - (2 - Amino - benzyl) - 1 - phenyl - 2 - methylamino-propanol- (1) is obtained (1) by reducing N - (2 - aminobenzyl) - 2 - methylamino-propiophenone with NaBH 4 , or (ii) by reacting 2-nitrobenzyl chloride with 1-phenyl-2- methylamino-propanol-(1) to yield N-(2-nitrobenzyl) - 1 - phenyl - 2 - methylamino - propanol - (1) and reducing the nitro group with Raney nickel; (b) N - (2 - acetamino - benzyl) - 1 - phenyl - 2 - methylamino - propanol - (1) is obtained by acetylating compound (a) above; (c) 1,2,3,4 - tetrahydro - 2 - methyl - 4 - phenyl - 8-amino -isoquinolone is obtained by condensation of N-methyl-N-(2-aminobenzyl)-mandelic acid amide with H 2 SO 4 ; (d) N - (2 - amino - benzyl) - 1 - (3,4 - dimethylphenyl) - 2 - methylamino - propanol - 1 is obtained by reacting α-bromo-3,4-dimethyl-propiophenone with (2-nitrobenzyl)-methylamine then hydrogenating the NO 2  group and then reducing the CO group; (e) N - (2 - aminobenzyl) - 1 - phenyl - 2 - amino-propanol.(1) is obtained by hydrogenating a mixture of α-acetyl-benzyl alcohol and benzylamine to form 1-phenyl-2-aminopropanol-(1) which is reacted with 2-nitrobenzaldehyde and the product reduced at the nitro and azo-methine groups to form the above compound (e). Pharmaceutical compositions, having a centrally stimulating and thymoleptic action, comprise compounds of Formula I or physiologically tolerable salts thereof, together with a pharmaceutically suitable carrier, in forms suitable for oral or parenteral administration.