Alkylation of 2-mercapto-4-methylpyrimidine (I) with iodomethane and NaOH affords 2-methylthio-4-methylpyrimidine (II). Condensation of (II) with methyl 4-fluorobenzoate (III) in the presence of sodium hexamethyldisilazide produces ketone (IV), which is further oxidized to dione (V) with DMSO/HBr. Ring closure of dione (V) with glyoxal dimethyl acetal (VI) in the presence of ammonium acetate leads to imidazole (VII). Acid-catalyzed transketalization of (VII) with the dihydroxy ester (VIII) yields the 1,3-dioxane derivative (IX) as a 3:2 mixture of cis- and trans- isomers. After chromatographic separation of the desired trans- isomer, oxidation of the methylthio group with mCPBA furnishes sulfone (X)

Attachment of the sulfonylpyrimidine (X) to a Merrifield thiol resin in the presence of NaH in DMF provides resin-bounded compound (XI). Then, saponification of the methyl ester group of (XI) yields carboxylic acid (XII). After formation of the corresponding acid chloride (XIII), coupling with N-methylpiperazine (XIV) gives rise to amide (XV). Sulfide group oxidation in (XV) leads to the sulfonylpyrimidine resin (XVI). Finally, cleavage from the resin in the presence of cyclopropylmethylamine (XVII) in hot NMP affords the target 2-aminopyrimidine derivative