【药物名称】Sumanirole maleate, U-95666(free base), U-95666E, PNU-95666E, PNU-95666A, U-95666A
化学结构式(Chemical Structure):
参考文献No.447273
标题:Synthesis of the selective D2 receptor agonist PNU-95666E from D-phenylalanine using a sequential oxidative cyclization strategy
作者:Romero, A.G.; et al.
来源:J Org Chem 1997,62(19),6582
合成路线图解说明:

D-Phenylalanine (I) was protected as the methyl carbamate (II) by acylation with methyl chloroformate under Schotten-Baumann conditions. The N-methoxy amide (III) was then prepared by coupling of (II) with O-methyl hydroxylamine in the presence of EDC. Cyclization of (III) to the N-methoxy quinolinone (IV) was accomplished by treatment with bis(trifluoroacetoxy)iodobenzene in the presence of trifluoroacetic acid. Simultaneous reduction of the N-methoxy lactam and carbamate functions of (IV) by means of borane-methyl sulfide complex provided diamine (V). The aliphatic amino group of (V) was then selectively protected as the benzyl carbamate (VI) by using N-(benzyloxycarbonyloxy)succinimide at -40 C. Reaction of (VI) with phosgene, followed by treatment of the intermediate carbamoyl chloride with O-methyl hydroxylamine gave rise to the N-methoxy urea derivative (VII). This was cyclized with bis(trifluoroacetoxy)iodobenzene to the imidazoquinolinone (VIII). The N-methoxy and N-benzyloxycarbonyl groups of (VIII) were then removed by hydrogenolysis in the presence of Pearlman's catalyst, and the title compound was finally converted to the corresponding maleate salt.

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