合成路线1

In an alternative method, 2-thiobarbituric acid (XIII) is alkylated with 1-iodopropane and NaOH in N-methylpyrrolidone to afford the 2-(propylsulfanyl)pyrimidine (XIV). Diazotization of p-toluidine (XV) with NaNO2 and HCl, followed by coupling of the intermediate diazonium salt with pyrimidine (XIV) in the presence of NaOAc, produces the diazo adduct (XVI). After chlorination of (XVI) with POCl3, reductive cleavage of the diazo compound (XVII) with H2 and Pt/C gives 5-amino-4,6-dichloro-2-(propylsulfanyl)pyrimidine (XVIII). Subsequent condensation of (XVIII) with the cyclopentylamino compound (XIX) in ethanolic triethylamine at 120 °C in a pressure vessel provides the diaminopyrimidine (XX), which is further converted to the azapurine (XXI) by treatment with NaNO2 in acetic acid. Then, substitution of chloride (XXI) with 2-(3,4-difluorophenyl)cyclopropylamine (X) in the presence of triethylamine in acetonitrile affords the acetonide (XII), which is finally hydrolyzed to the title compound as in the above method (3). Scheme 2.