合成路线1

In a different synthetic strategy, L-serine methyl ester (X) was protected as the N-benzyl derivative (XI) by reductive alkylation with benzaldehyde and NaBH4. Ammonolysis of ester (XI) then produced N-benzyl serinamide (XII). Subsequent reduction of the amide function of (XII) employing borane-dimethyl sulfide complex gave diamine (XIII). This was condensed with the chloropyrimidine (XIV) to afford adduct (XV). After protection of the exocyclic amine with di-tert-butyl dicarbonate, alcohol (XVI) oxidation with Dess-Martin periodinane reagent yielded aldehyde (XVII). Reductive coupling of (XVII) with p-aminobenzoyl glutamic acid (XVIII), followed by acidic Boc group deprotection, led to the triaminopropane derivative (XIX). Catalytic hydrogenation of the nitro group of (XIX) and N-debenzylation over Pd/C yielded the pteridine ring precursor (XX).