合成路线1

Esterification of 2-amino-4,6-dimethoxybenzoic acid (XVI) with diazomethane in ethanol gives the corresponding methyl ester (XVII), which is cyclized with formamidine (XVIII) in refluxing 2-methoxyethanol to yield 5,7-dimethoxyquinazolin-4(3H)-one (IXX). Selective demethylation of compound (IXX) by means of MgBr2 in refluxing pyridine affords 5-hydroxy-7-methoxyquinazolin-4(3H)-one (XX), which is condensed with pivaloyloxymethyl chloride (POM-Cl) and NaH in DMF to provide the protected quinazolinone (XXI). Condensation of compound (XXI) with 4-hydroxytetrahydropyran (X) by means of PPh3 in dichloromethane gives 7-methoxy-5-(tetrahydropyran-4-yloxy)quinazolin-4(3H)-one (XXII), which is demethylated by means of PhSH and K2CO3 in NMP at 195 °C to yield the 7-hydroxyquinazolinone derivative (XXIII). Acylation of compound (XXIII) with acetic anhydride affords the 7-acetoxy derivative (XXIV) , which is treated with POCl3 at 80 °C to provide 7-acetoxy-4-chloro-5-(tetrahydropyran-4-yloxy)quinazoline (XXV). Condensation of (XXV) with 4-amino-5-chloro-1,3-benzodioxole (II) in hot isopropanol gives adduct (XXVI), which is treated with ammonia in methanol to afford the 7-hydroxyquinazoline derivative (IV). Finally, this compound is condensed with 1-(2-chloroethyl)-4-methylpiperazine (XXVII) by means of K2CO3 in DMF (3, 4). Scheme 3.