METHOD OF PREPARING BENZOIC ACID DERIVATIVE INTERMEDIATE ANDBENZOTHIOPHENE PHARMACEUTICAL

摘要

The present invention provides a novel process for preparing novel compounds of formula I wherein R<1> and R<2> each are independently C1-C4 alkyl, or combine to form piperidinyl, pyrrolidinyl, methylpyrrolidinyl, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; and n is 2 or 3; or a pharmaceutically acceptable salt thereof, comprising a) reacting a haloalkyl amine of formula III wherein X is a halogen; and R<1>, R<2>, and n are as defined above, with a compound of formula IV wherein R is C1-C6 alkyl, in the presence of an alkyl acetate solvent and a base; b) extracting the reaction product of step a) with an aqueous acid; and c) cleaving the ester of the reaction product from step b) to form an acid. The present invention further provides a novel process for preparing compounds of formula V wherein R<1> and R<2> each are independently C1-C4 alkyl, or combine to form piperidinyl, pyrrolidino, methylpyrrolidino, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; R<3> and R<4> each are H or a hydroxy protecting group; and n is 2 or 3; or a pharmaceutically acceptable salt thereof, comprising a) reacting a haloalkyl amine of formula III wherein X is a halogen; and R<1>, R<2>, and n are as defined above, with a compound of formula IV wherein R is C1-C6 alkyl, in the presence of an alkyl acetate solvent and a base; b) extracting the reaction product from step a) with an aqueous acid; c) cleaving the ester of the reaction product from step b) to form an acid; d) reacting the extracted product from step c) with a compound of formula V wherein R<3> and R<4> are as defined above, or a pharmaceutically acceptable salt thereof; e) optionally removing the R<3> and R<4> hydroxy protecting groups of the reaction product form step d); and f) optionally forming a salt of the reaction product from either steps d) or step e).