Condensation of S-methylisothiourea (I) and cyano acetate derivative (II) by means of NaOMe in MeOH affords pyrimidine derivative (III), whose hydroxy group is converted into chloro by means of refluxing POCl3, yielding derivative (IV). Alkylation of (IV) with cyclopentylamine (V) and Et3N in CH2Cl2 provides derivative (VI), whose nitrile group is then reduced by means of LiAlH4 in THF to afford aminomethyl compound (VII). Treatment of (VII) with 1,1-carbonyldiimidazole (CDI) in refluxing THF gives pyrimidopyrimidinone (VIII), whose methylsulfanyl group is oxidized with 3-phenyl-2-(phenylsulfonyl)oxaziridine (IX) in CHCl3 to afford methyl sulfoxide derivative (X). Displacement of the methyl sulfoxide group of (X) with substituted aniline (XI) in TFA/acetonitrile yields 3,4-dihydropyrimidopyrimidinone (XII), which is finally oxidized by means of KOtBu in THF or DMSO.

Condensation of S-methylisothiourea (I) and cyano acetate derivative (II) by means of NaOMe in MeOH affords pyrimidine derivative (III), whose hydroxy group is converted into chloro by means of refluxing POCl3, yielding derivative (IV). Alkylation of (IV) with cyclopentylamine (V) and Et3N in CH2Cl2 provides derivative (VI), whose nitrile group is then reduced by means of LiAlH4 in THF to afford aminomethyl compound (VII). Treatment of (VII) with 1,1-carbonyldiimidazole (CDI) in refluxing THF gives pyrimidopyrimidinone (VIII), whose methylsulfanyl group is oxidized with 3-phenyl-2-(phenylsulfonyl)oxaziridine (IX) in CHCl3 to afford methyl sulfoxide derivative (X). Displacement of the methyl sulfoxide group of (X) with substituted aniline (XI) in TFA/acetonitrile yields 3,4-dihydropyrimidopyrimidinone (XII), which is finally oxidized by means of KOtBu in THF or DMSO.