Process for the synthesis of nucleoside analogs

A method of making a 2′,3′-O-alkylidene β-nucleoside analog, comprising reacting a 2′,3′-O-alkylidene β-furanosyl halide having the structural formula:

• in which:
• R3 and R4 are each independently selected from the group consisting of hydrogen, (C2-C6)alkenyl and (CH2)nQ, where n is an integer from 1 to 6;
• or R3 and R4 together form a ring of from 3 to 6 carbons, the ring containing 0 to 3 heteroatoms selected from oxygen and nitrogen, and optionally substituted by one or more Q;
• R5 and R6 are each independently selected from the group consisting of hydrogen, Q, (C1-C6) alkyl and (C1-C6) alkyl substituted with one or more Q;
• Q is selected from the group consisting of hydrogen, —NO2, —N3, —CN, —SR7, —CX3, —CF3, —X, —OR7, —C(O)OR7, —C(O)R7, —NR7R7, —NH—SO2—R7, and —SO2R7;
• each R7 is independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C5-C20)aryl, substituted (C5-C20)aryl, 5-20 membered heteroaryl, substituted 5-20 membered heteroaryl, and a protecting group;
• X is halogen;
• and
• Y is chloro or bromo;
• with a heterocycle having a ring nitrogen capable of forming a covalent bond with the anomeric carbon of a furanose or furanose analog in dimethylsulfoxide (DMSO) or in a polar mixture of solvents comprising DMSO in the presence of a strong base.