Preparation of 2'-fluoro-2'-alkyl-substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives
First Claim
Patent Images
1. A method of synthesizing a 2′
- -deoxy-2′
-fluoro-2′
-C-methyl-β
-D-ribofuranosyl nucleoside of the following formula;
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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-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.
152 Citations
83 Claims
-
1. A method of synthesizing a 2′
- -deoxy-2′
-fluoro-2′
-C-methyl-β
-D-ribofuranosyl nucleoside of the following formula;
- View Dependent Claims (2, 49, 50)
- -deoxy-2′
-
3. A 3,5-di-O-protected-2-deoxy-2-fluoro-2-C-methyl-D-ribono-γ
- -lactone of the following general formula;
- -lactone of the following general formula;
- 4. The cyclic sulfite (IIIa), cyclic sulfate (IIIb), and cyclic carbonate (IIIc) of the following general formula:
- 5. The cyclic sulfate (IIIb) of the following general formula:
- 16. A compound of the following general formula 51B:
- 20. A compound of the following general formula 52B:
- 25. A process for the preparation of a compound of formula 53 comprising:
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28. A compound of the following general formula 53B:
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29. A process for the preparation of a compound of the formula 53B comprising:
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(a) heating a compound of the formula 51B or 52B;
with an acid with a solvent;
wherein the solvent is selected from one or more of the group consisting of MeOH, EtOH, i-PrOH, CH3CN, THF, and water;
(b) optionally, followed by azeotropic distillation in benzene or toluene in presence of an acid. - View Dependent Claims (30, 31)
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32. A compound of the following general formula, 53C:
- 33. A process for the preparation of a compound of formula 53C comprising selective protection of the 5-hydroxy of the formula 53B:
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37. A compound of the following general formula, 49B:
- 41. A compound of the following general formula, 56:
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46. A compound of the formula, 57:
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47. A process for the preparation of a compound of the formula I:
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48. A process for the preparation of the L-enantiomers, IB-L
- 51. An intermediate of the formula 42B, 42B-L, 42C, 42D:
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52. A 2-alkyl-4,5-di-O-protected-2,3-dihydroxy-pentanoic-acid ester of the following general formula (42B) and its isomer (42B-L):
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69. A 3,5-di-O-protected-2-deoxy-2-fluoro-2-C-methyl-D-ribono-γ
- -lactone of the following general formula (49B) and its L-isomer (49B-L);
- View Dependent Claims (70, 71)
- -lactone of the following general formula (49B) and its L-isomer (49B-L);
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72. A method for the synthesis of an intermediate in the synthesis of a lactone 53,
- 75. A compound of the following general formula 51B:
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79. A compound of the following general formula 52B:
- 80. A process for the preparation of a compound of formula 53 comprising:
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83. A process for the preparation of a compound of the formula 49B:
Specification