Patent ID: 6693197
Filing Date: 2004-02-17
Classification: A61P,C07D

Abstract:
A method of making compounds of Formula I: whereinR1 is hydrogen, hydroxy, halo, cyano, carboxamido, carboalkoxy of two to six carbon atoms, alkyl of 1 to 6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, amino, mono- or di-alkylamino in which each alkyl group has 1 to 6 carbon atoms, alkanamido of 2 to 6 carbon atoms, or alkanesulfonamido of 1 to 6 carbon atoms; R2, R3, R4, and R6 are, independently, hydrogen, hydroxy, halo, cyano, carboxamido, carboalkoxy of two to six carbon atoms, trifluoromethyl, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, amino, mono- or di-alkylamino in which each alkyl group has 1 to 6 carbon atoms, alkanamido of 2 to 6 carbon atoms, or alkanesulfonamido of 1 to 6 carbon atoms R5 is hydrogen or alkyl of 1 to 6 carbon atoms; A dotted line represents an optional double bond; A and D are selected from carbon, substituted by R1, and nitrogen, provided that at least one of A and D is nitrogen; E and G are carbon, substituted by R1; and Z is N or CR6; or pharmaceutically acceptable salts thereof, comprising the steps of: a) halogenating a compound of the formula: wherein R1 is alkyl of 1-6 carbon atoms;with a halogenating reagent to afford a compound of the formula: wherein X is Br, Cl, or I;b) dealkylating the compound of Formula 3 in an acid to afford a compound of the formula: c) alkylating the compound of Formula 4 with Râ€³ protected glycidyl ethers wherein Râ€³ is benzyl or substituted benzyl to afford compound of the formula: d) cyclizing the compound of Formula 5 with palladium or copper catalyst to afford a compound of the formula: e) debenzylating the compound of Formula 6 to afford the compound of the formula: f) activating the hydroxy moiety of the compound of Formula 7 with a sulfonating reagent to afford a compound of the formula: wherein Râ€²â€³ is an aryl- or alkyl- sulfonate; andg) coupling the compound of Formula 8 with the appropriate azaheterocycle of Formula 9 in the presence of base to provide a compound of Formula I