Patent ID: 6380397
Filing Date: 2002-04-30
Classification: C07D

Abstract:
A process for preparing a compound of the formula I or a pharmaceutically acceptable salt or prodrug derivative thereof wherein:R1 is selected from the group consisting of C7-C20alkyl; â€ƒwhere;R10 is selected from the group consisting of halo, C1-C10alkyl, C1-C10alkoxy, â€”Sâ€”(C1-C10alkyl) and halo(C1-C10)alkyl, and t is an integer from 0 to 5 both inclusive; R2 is selected from the group consisting of hydrogen, halo, C1-C3alkyl, C3-C4cycloalkyl, C3-C4cycloalkenyl, â€”Oâ€”(C1-C2alkyl), â€”Sâ€”(C1-C2alkyl), aryl, aryloxy, and heterocyclic ring; R4 is selected from the group consisting of â€”CO2H, â€”SO3H, and â€”P(O)(OH)2 or salt or prodrug derivatives thereof; and R5 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, halo(C1-C6)alkoxy, halo(C2-C6)alkyl, bromo, chloro, fluoro, iodo and aryl; which process comprises the steps of a) halogenating a compound of formula X where R8 is (C1-C6)alkyl, aryl or heterocyclic ring; with SO2Cl2 to form a compound of formula IX b) hydrolyzing and decarboxylating a compound of formula IX to form a compound of formula VIII c) alkylating a compound of formula VII with a compound of formula VIII to form a compound of formula VI d) aminating and dehydrating a compound of formula VI with an amine of the formula R1NH2 in the presence of a solvent that forms an azeotrope with water to form a compound of formula V e) oxidizing a compound of formula V by heating with a base and a compound of the formula RSOX where R is â€”(C1-C6)alkyl, or aryl or substituted aryl and X is â€”(C1-C6)alkoxy, halo or â€”OCO2 (C1-C6)alkyl to form a compound of formula IV f) alkylating a compound of the formula IV with an alkylating agent of the formula XCH2R4a where X is a leaving group and R4a is â€”CO2R4b, â€”SO3R4b, â€”P(O)(OR4b)2, or â€”P(O)(OR4b)H, where R4b is an acid protecting group, to form a compound of formula III g) reacting a compound of formula III with oxalyl chloride and ammonia to form a compound of formula II h) optionally hydrolyzing a compound of formula II to form a compound of formula I; and i) optionally salifying a compound of formula I.