Process for preparation of substantially pure fosamprenavir calcium and its intermediates

摘要

The present invention relates to fosamprenavir calcium (Ia) substantially free of isomer impurity, (3R)tetrahydro-3-furanyl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-(phosphonooxy)propyl carbamate (Ib), and its process for preparation thereof. The present invention also provides fosamprenavir calcium intermediate, (S)-3-tetrahydrofuranyl-N-succinimidyl carbonate (IIa) substantially free of (R)-3-tetrahydrofuranylsuccinimidyl carbonate (IIb) and its process for preparation thereof.

主权项

1. A process for preparation of fosamprenavir calcium (Ia) substantially free of R-isomer impurity (Ib) comprising: a) analyzing the level of intermediate R-isomer impurity (IIb) in a sample of (S)-3-tetrahydrofuranyl-N-succinimidyl carbonate (IIa); b) selecting a sample of (S)-3-tetrahydro furanyl-N-succinimidyl carbonate (IIa) containing less than 0.2% area percentage of HPLC of intermediate R-isomer impurity (IIb); c) reacting said (S)-3-tetrahydrofuranyl-N-succinimidyl carbonate (IIa) with (2R,3S)—N-(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-nitrobenzene sulphonamide (III) to obtain (3S)-tetrahydro-3-furanyl N-[(1S,2R)-1-benzyl-2-hydroxy-3-(N-isobutyl-4-nitrobenzene sulphonamido)propyl]carbamate (IV); and d) conversion of compound (IV) to fosamprenavir calcium (Ia).