Patent ID: 7435805

Claim:
A process for the preparation of a compound of the formula wherein: A is a bivalent radical selected from —C(O)—, —C(O)NH—, —NHC(O)—, —N(R 11 )—CH 2 —, —CH 2 —N(R 11 )—, —CH(NR 11 R 12 )— and —C(═N—OR 13 )—; R 1 is cladinosyl of formula (V), OH or together with R 2 forms a keto group provided that when R 1 together with R 2 forms a keto group R 4 is not H; R 2 is H or together with R 1 forms a keto group; R 3 is desosaminyl of formula (VI) or hydroxyl; R 4 is hydrogen, C 1-4 alkyl, or C 2-6 alkenyl optionally substituted by 9 to 10 membered fused bicyclic heteroaryl; R 5 is hydrogen or fluorine; R 6 is hydroxyl, —NH 2 , or together with R 7 forms a keto group or ═NR 10; R 7 is hydrogen, —NH 2 , or together with R 6 forms a keto group or ═NR 10; R 8 is H or a carbobenzoxy group; R 9 is H, CH 3 or a carbobenzoxy group; R 10 is hydrogen or C 1-6 alkyl; R 11 and R 12 are each independently hydrogen, C 1-6 alkyl, aryl, heteroaryl, heterocyclyl, sulfoalkyl, sulfoaryl, sulfoheterocyclyl or —C(O)R 10 , wherein the alkyl, aryl and heterocyclyl groups are optionally substituted by up to three groups independently selected from R 14 ; R 13 is hydrogen, —C 1-6 alkyl, C 2-6 alkenyl, —(CH 2 ) a aryl, —(CH 2 ) a heterocyclyl, or —(CH 2 ) a O(CH 2 ) b OR 10 ; R 14 is halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, C1-6alkoxy or aryloxy, C1-6alkythio or arylthio, —NH 2 , —NH(C 1-6 alkyl) or —N(C 1-6 alkyl) 2 ; and a and b are each independently integers from 1 to 4; comprising the step of O-methylating at the 11 position a compound of formula (IV) wherein A and R 1 -R 14 are as hereinbefore defined, with a diazomethane of formula (III) R 2 —CH N 2 (III) wherein: R 2 is hydrogen, in the presence of a catalyst selected from the group consisting of TiCl 4 , SnCl 2 and boric acid, and in an inert organic solvent selected from the group consisting of acetone, ethanol, acetonitrile and N,N-dimethylformamide, wherein the molar ratio of a compound of formula (IV) to catalyst is 1: 0.25 to 1: 2, and wherein said methylating step results in substantial regioselectivity.