Preparation of 2′-fluoro-2′-alkyl-substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives
The present invention provides (i) processes for preparing a 2′-deoxy-2′-fluoro-2′-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-ß-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.
1. A compound of formula 51B:
wherein:
each R 1 is independently (C 1 -C 6 ) alkyl, phenyl or benzyl; or two R 1 with the carbon attached thereto form a cyclopentyl or cyclohexanyl group;
R 2 is hydrogen, (C 1 -C 6 ) alkyl, hydroxymethyl, methoxymethyl, halomethyl, vinyl, halovinyl, ethynyl, haloethynyl, allyl or haloallyl;
R 3 is (C 1 -C 6 ) alkyl, hydroxymethyl, methoxymethyl, halomethyl, vinyl, halovinyl, ethynyl, haloethynyl, allyl or haloallyl;
R 4 is hydrogen, aryl, arylalkyl or (C 1 -C 6 ) alkyl;
Nu is F, Cl, Br, N 3 , CN, NO 3 , CF 3 , SCN, OR or NR 2 where each R is independently arylalkyl or (C 1 -C 6 ) alkyl; and
M + is tetrabutylammonium, tetraethylammonium, tetramethylammonium, sodium, potassium, cesium, rubidium or silver.
2. A compound of formula 52B:
wherein:
each R 1 is independently (C 1 -C 6 ) alkyl, phenyl or benzyl; or two R 1 with the carbon attached thereto form a cyclopentyl or cyclohexanyl group;
R 2 is hydrogen, (C 1 -C 6 ) alkyl, hydroxymethyl, methoxymethyl, halomethyl, vinyl, halovinyl, ethynyl, haloethnyl, allyl or haloallyl;
R 3 is (C 1 -C 6 ) alkyl, hydroxymethyl, methoxymethyl, halomethyl, vinyl, halovinyl, ethynyl, haloethynyl, allyl or haloallyl;
R 4 is hydrogen, aryl, arylalkyl or (C 1 -C 6 ) alkyl; and
Nu is F, Cl, Br, N 3 , CN, NO 3 , CF 3 , SCN, OR or NR 2 where each R is independently arylalkyl or (C 1 -C 6 ) alkyl.