Patent ID: 8344162

Claim:
A method of making a compound of formula (I): or a pharmaceutically acceptable salt, ester, amide, clathrate with a cyclodextrin or solvate in a solution phase thereof; or a single stereoisomer or mixture thereof; wherein: R 3 , R 4 and R 5 are independently bromine, chlorine, fluorine, carboxy, hydrogen, hydroxy, hydroxymethyl, methanesulfonamido, nitro, cyano, sulfamyl, trifluoromethyl, —CHF 2 , —SO 2 N(R 8 )R 9 , —OCF 3 , C 2 -C 7 alkanoyloxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 7 -C 12 aralkoxy, C 2 -C 7 alkoxycarbonyl, C 1 -C 6 thioalkyl, aryl or —N(R 6 )R 7 ; and R 6 , R 7 , R 8 , and R 9 are each independently selected from hydrogen, acetyl, methanesulfonyl or C 1 -C 6 alkyl; which method comprises the following: a) reacting a compound of formula (1a): with a compound of formula (2a): under suitable condensation conditions to form a product; b) reacting the product of a) with a compound of formula (5): wherein Q is a leaving group and R 3 , R 4 and R 5 are as defined above, under suitable ether coupling conditions to form a product; c) reacting the product of b) under suitable cyclization conditions to form a compound of formula (6): wherein each R 2a is O or H 2 where at least one R 2a is O, R is H, C 2 -C 5 acyl or an oxygen-protecting group and R 3 , R 4 and R 5 are as defined above; and d) reducing the compound of formula (6) under suitable conditions to form a compound of formula (I), as set forth above; e) optionally treating the compound of formula (I) with a suitable reagent or solvent to form the pharmaceutically acceptable salt, ester, amide, clathrate with a cyclodextrin or solvate in a solution phase thereof.