Patent ID: 8053451
Filing Date: 2011-11-08
Classification: A61K,A61P,C07D

Abstract:
1. A process for preparing (2S)-(4E)-N-methyl-5-(5-isopropoxy-3-pyridinyl)-4-penten-2-amine or a corresponding hydroxybenzoate salt, comprising the steps of: a) performing a Heck coupling reaction between a 3-halo-5-isopropoxypyridine and a compound of the formula (S)—CH b) deprotecting the protected amine group, or c) performing a Heck coupling reaction between a 3-halo-5-isopropoxypyridine and a compound of the formula (R)—CH d) converting the OH group to an NHCH e) forming a hydroxybenzoate salt by reaction of the mixture with a hydroxybenzoic acid of the formula: where the hydroxy group can be present at a position ortho, meta or para to the carboxylic acid group, Z represents a non-hydrogen substituent selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocyclyl, substituted heterocyclyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, F, Cl, Br, I, NR′R″, CF where q is an integer from 1 to 6 and R′ and R″ are individually hydrogen, C and j is a number from zero to three, representing the number of Z substituents that can be present on the ring, wherein the molar ratio of the E-metanicotine to hydroxybenzoic acid ranges from 1:2 to 2:1, f) isolating the (2S)-(4E)-N-methyl-5-(5-isopropoxy-3-pyridinyl)-4-penten-2-amine hydroxybenzoate salt, and g) optionally converting the (2S)-(4E)-N-methyl-5-(5-isopropoxy-3-pyridinyl)-4-penten-2-amine hydroxybenzoate salt to (2S)-(4E)-N-methyl-5-(5-isopropoxy-3-pyridinyl)-4-penten-2-amine.