Preparation of 2′-fluoro-2′-alkyl-substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives

Patent metadata

Field	Value
Publication number	US-10577359-B2
Application number	US-201715425198-A
Country	US
Kind code	B2
Filing date	Feb 6, 2017
Priority date	Sep 14, 2004
Publication date	Mar 3, 2020
Grant date	Mar 3, 2020

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Gilead Pharmasset Llc

Inventors

• Chun Byoung-Kwon
• Du Jinfa
• Rachakonda Suguna
• Wang Peiyuan

Classifications

• A61P31/14

  for RNA viruses · CPC title

• C07D307/20

  Oxygen atoms · CPC title

• C07H15/203

  Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems · CPC title

• C07D317/30

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D307/33

  in position 2, the oxygen atom being in its keto or unsubstituted enol form · CPC title