5-METHYLURIDINE METHOD FOR PRODUCING FESTINAVIR

摘要

The NRTI compound festinavir is made using 5-methyluridine as a starting material, followed by Claisen rearrangement.

主权项

1. A method for making the compound of Formula I which comprises: (1) Treating 5-Methyluridine  with acid and acetaldehyde to produce the compound 1 (2) Reacting compound 1 with 4-biphenyl acid chloride and pyridine in solvent to yield compound 2 (3) Reacting compound 2 with Lewis acid and triethylamine (Et3N) in solvent, followed by reaction with aqueous acid or methanolic NH4F, to produce compound 3 (4) Treating compound 3 with iodine (I2), PPh3 and imidazole with THF solvent to produce compound 4 (5) Performing iodide elimination reaction by heating a solution of compound 4 in toluene in the presence of a Lewis base to yield compound 5 (6) Conducting a Claisen rearrangement by heating compound 5 in benzonitrile or toluene to produce compound 6 (7) Reacting compound 6 with a TMSCl/Et3N mixture, followed by NfF, and then warming in the presence of P-base to produce compound 7  and (8) Removing the ester protecting group by hydrolysis of compound 7 to yield the compound of Formula I.