PROCESS FOR THE SYNTHESIS OF HIV PROTEASE INHIBITORS

摘要

1. A process for the preparation of the compound of formula (I) comprising: i) reacting a p-nitrophenylsulfonyl group with a compound of formula (A) in which P is an amine-protecting group; ii) deprotecting the resultant compound of step i); iii) reacting the resultant compound of step (ii) with a tetrahydrofuryloxy carbonyl group; or reacting the resultant compound of step ii) with phosgene, or equivalent, and reacting the resultant intermediate with (S)-tetrahydro-3-furanol; and iv) reducing the resultant compound of step iii) to form a compound of formula (I). 2. A process as claimed in claim 1 in which the protecting group P in the compound of formula (A) is an alkyl, aryl, benzyl or hetero carbamate, alkyl or aryl amide, or silyl group. 3. A process as claimed in claim 2 in which the protecting group P in the compound of formula (A) is t-butyl carbamate. 4. A process as claimed in claim 1 in which the p-nitrophenylsulfonyl group in step i) is a p-nitrophenyisulfonyl halide. 5. A process as claimed in claim 1 in which step i) is carried out in dimethylacetamide or toluene. 6. A process as claimed in any preceding claim in which step ii) is carried out in ethanol or toluene. 7. A process as claimed in claim 1 in which the step ii) product is crystallised as a solvate. 8. A process as claimed in claim 1 in which step iii) is carried out by reacting (S)-tetrahydro-3-furanol with 1,1'-carbonyidiimidazole and the step ii) product in a single step. 9. A process as claimed in claim 8 in which step iii) is carried in ethyl acetate. 10. A process as claimed in claim 1 in which step iv) is carried out by treating the step iii) product with palladium under a hydrogen atmosphere. 11. A process as claimed in claim 10 in which step iv) is carried out in isopropanol. 12. The compound (2R,3S)-N-(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-nitrobenzene sulphonamide hydrochloride and solvates thereof.