Abstract: Provided is a method for preparing islatravir, including: 1) subjecting compound of Formula II as a raw material to selective hydroxyl protection reaction to obtain compound of Formula III, 2) subjecting the compound of Formula III to hydroxyl oxidation reaction to obtain compound of Formula IV; 3) subjecting the compound of Formula IV and dimethyl diazomethylphosphonate to reaction under an alkaline condition to obtain compound of Formula V; 4) subjecting the compound of Formula V to protecting group conversion reaction to obtain compound of Formula VI; 5) subjecting the compound of Formula VI to glycosylation reaction to obtain compound of Formula VII; 6) subjecting the compound of Formula VII to selective deprotection reaction to obtain compound of Formula VIII; 7) subjecting the compound of Formula VIII to deoxidation reaction to obtain compound of Formula IX; and 8) subjecting the compound of Formula IX to debenzylation reaction to obtain the islatravir.

Abstract: The present disclosure provides a preparation method of a 2?-substituted pyrimidine nucleoside, including the following steps: subjecting a compound of Formula I or Formula II to a series of process including dehydration, selective 5?-protection, ring-opening reaction using magnesium alkoxide and deprotection to obtain a 2?-substituted pyrimidine nucleoside of Formula VII or Formula VIII. In the present disclosure, the preparation method has desirable universality for different substrates; the ring-opening with a protected anhydrous pyrimidine nucleoside improves a solubility of the substrate, with milder reaction conditions than those of a traditional synthetic route; the formation of a dimer is avoided during the ring-opening to improve the yield; in addition, an intermediate (5?-O-bis-p-methoxytrityl-protected 2?-substituted pyrimidine nucleoside) can be directly used in synthesis of a corresponding phosphoramidite monomer, with a wider potential for use.