GB1186938A - Tertiary 1,3-Aminoalcohols - Google Patents

Abstract

1,186,938. Tertiary 1,3-aminoalcohols. UPJOHN CO. 24 Aug., 1967 [26 Sept., 1966], No. 39082/67. Heading C2C. Novel compounds of Formula II wherein n is 1-4; -N Z is a heterocyclic radical with 5-10 atoms in the ring; R<SP>1</SP>, R<SP>11</SP> and R<SP>111</SP> are selected from hydrogen atoms, halogen atoms, C 1-6 alkyl, C 1-6 alkoxy and -CF 3 radicals; and R 1 , R 2 and R 3 are selected from hydrogen atoms, C 1-6 alkyl, C 1-6 alkoxy and -CF 3 radicals and their C 1-4 alkyl ethers, esters with C 2-8 straight-chain alkanoic acids, benzoic acid, mono-substituted benzoic acids, phenylacetic acid and phenyl-propionic acid, N-oxides, acid addition salts and quaternary C 1-12 alkyl ammonium halide salts are prepared by the following processes: (a) where the free hydroxy compound is required by treating a compound of Formula I with a Grignard reagent V wherein X is iodine or bromine, followed by decomposition of the resultant complex with water, (b) where the ether is required, by treating a compound II with sodamide in liquid ammonia followed by an alkyl bromide or iodide, (c) where the ester is required, by treating a compound I with butyl lithium and treating the salt formed with the appropriate acyl chloride, and (d) where the N-oxide is required, by treating a compound I with a peracid, followed in (a), (b), (c) or (d), where desired, by salt formation. Electrocardiographic jellies contain as the active ingredient a quaternary ammonium halide salt of compounds (II). A suitable jelly contains 5 parts glycerol, 10 parts starch, 60 parts quaternary ammonium salt and 100 parts water. The starting materials of Formula I are prepared by reacting the appropriate cycloalkanone with an heterocyclic amine to form an enamine and reacting this enamine with the appropriate benzoyl chloride, the benzoyl radical of which attaches itself to the 2-position of the cycloalkenyl moiety of the enamine. After hydrolysis the 2-(benzoyl or substituted benzoyl)-cycloalkanone is reacted with the appropriate heterocyclic amine. The thus-obtained (phenyl or substituted phenyl) (2-heterocyclicamino-1-cycloalken-1-yl) ketone is hydrogenated to give the starting material I. Pharmaceutical compositions comprise the compounds (II) and a carrier therefor. Compositions may be in a form suitable for enteral or parenteral administration and are useful in the treatment of oedema associated with hepatic disease, oedema and toxaemia of pregnancy, hypertensive vascular disease, premenstrual fluid retention and congestive heart failure.