Phenalkylamine und Verfahren zu deren Herstellung

摘要

1,212,550. Benzyl alcohol derivatives. MERCK & CO. Inc. 6 May, 1968 [8 May, 1967], No. 21351/68. Heading C2C. Compounds of the general Formula (I) (R1 = H, alkyl substituted alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkoxy, phenyl, substituted phenyl, benzyl, substituted benzyl or heterocyclic radical; R2 = H, alkyl phenyl, substituted phenyl; or -CR1R2 = alicyclic or heterocyclic ring; R3= H, phenyl, alkyl; R4 = H, C 1-5 alkyl; X = H, halogen, alkyl, alkoxy, CF 3 , phenyl; n = 0 when the R1-C or R2-C bond is unsaturated or 1 when both bonds are saturated) and salts thereof are prepared by (a) reacting a compound of the Formula (III) with a C 2-6 alkanoic acid anhydride or C 2-6 alkanoyl halide to form a compound of the formula reacting the product with a compound of the formula (X2 = halogen, sulphonic ester or quaternary ammonium radical) to form a compound of the Formula (VI) and deacylating the product, (b) reacting a compound of the Formula (III) with R1R2 - CHX1 (R1 = phenyl, substituted phenyl; R2 = H, alkyl; X1=Cl, Br) in dimethyl sulphoxide or dimethylformamide in the presence of a strong base (c) catalytically reducing a compound of the Formula (VII) (R1 = H, alkyl, substituted alkyl, cycloalkyl or heterocyclic radical; R2 = H, alkyl; or -CR1R2 =saturated alicyclic or heterocyclic ring; R3=H, alkyl; X, n are as defined above) or (d) reacting a compound of the formula I (R4 = H) with a C 2-5 alkanoic acid anhydride or a C 1-4 alkyl formate and reducing the resulting amide, optionally followed in each case by resolution and/or salt formation. The preparation of 3 - methoxy - 6 - methylpropiophenone, 3 - methoxy - 6 - methyl - α- hydroxyiminopropiophenone, 3 - methoxy - 6- methyl - α - aminopropiophenone hydrochloride, 4 - bromo - 5 - fluoroanisole, 3 - amino - 5 - fluoroanisole hydrochloride, 3 - bromo - 5 - fluoroanisole, 5 - fluoro - 3 - methoxy propiophenone, 1 - (5- fluoro - 3 - methoxyphenyl) - 1 - propanol, 5- fluoro - 3 - methoxy - α - hydroxyiminopropio phenone, 3 - amino - 5 - methylanisole hydrochloride, 3 - bromo - 5 -methylanisole, 3 - methoxy- 5 - methylpropiophenone, 3 - methoxy - 5 - methyl- α - hydroxyiminopropiophenone, m - benzyloxy- α - bromopropiophenone, m - benzyloxy - α- dibenzylaminopropiophenone hydrochloride, threo m - benzyloxy - α - (1 - dibenzylaminoethyl)benzyl alcohol, racemic, (-)(lR,2R) and (+)(1S, 2S) threo m - hydroxy - α - (1 - aminoethyl)benzyl alcohol fumarate, racemic, (1R,2S) and (1S,2R) erythro and racemic, (1R,2R) and (1S,2S) threo m - hydroxy - α - (1 - acetamidoethyl) - benzyl alcohol and the m - benzyloxy derivatives of these compounds is described. The compounds of the invention are antihypertensive agents and inhibit gastric secretion; they may be administered in the form of pharmaceutical preparations containing them together with a carrier.