-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	34607
标题:	6-Phenylpyridyl-2-amine derivs.
作者:	Lowe, J.A. III; Whittle, P.J. (Pfizer Inc.)
来源:	EP 0891332; JP 1999510513; WO 9736871

合成路线图解说明: 2-Amino-6-bromopyridine (II) was prepared by reaction of 2,6-dibromopyridine (I) with ammonium hydroxide in a pressure bomb at 170 C. The amino group of (III) was subsequently blocked as the pyrrole derivative (IV) by condensation with 2,5-hexanedione (III). Diazotization of p-aminophenyl ethanol (V) followed by treatment with KI gave iodo derivative (VI). Subsequent reaction of (VI) with SOCl2 provided chloride (VII). Arylpyridine (VIII) was obtained by lithiation of bromopyridine (IV) with BuLi, followed by conversion to the corresponding organozinc compound with ZnCl2 and palladium-catalyzed coupling with iodide (VII). Pyrrole ring cleavage in (VIII) upon treatment with hydroxylamine furnished aminopyridine (IX). Subsequent condensation with N-Boc-piperazine (X) provided adduct (XI). After acid cleavage of the Boc group of (XI), alkylation of the resulting piperazine with phenacyl chloride (XII) yielded the title compound. Alternatively, the title compound was obtained by condensation of chloride (IX) with N-phenacylpiperazine (XIII).

参考文献No.	552682
标题:	A new class of selective and potent inhibitors of neuronal nitric oxide synthase
作者:	Lowe, J.A.; Qian, W.; Volkmann, R.A.; Heck, S.; Nowakowski, J.; Nelson, R.; Nolan, C.; Liston, D.; Ward, K.; Zorn, S.; Johnson, C.; Vanase, M.; Faraci, W.S.; Verdries, K.A.; Baxter, J.; Doran, S.; Sanders, M.; Ashton, M.; Whittle, P.; Stefaniak, M.
来源:	Bioorg Med Chem Lett 1999,9(17),2569

合成路线图解说明: 2-Amino-6-bromopyridine (II) was prepared by reaction of 2,6-dibromopyridine (I) with ammonium hydroxide in a pressure bomb at 170 C. The amino group of (III) was subsequently blocked as the pyrrole derivative (IV) by condensation with 2,5-hexanedione (III). Diazotization of p-aminophenyl ethanol (V) followed by treatment with KI gave iodo derivative (VI). Subsequent reaction of (VI) with SOCl2 provided chloride (VII). Arylpyridine (VIII) was obtained by lithiation of bromopyridine (IV) with BuLi, followed by conversion to the corresponding organozinc compound with ZnCl2 and palladium-catalyzed coupling with iodide (VII). Pyrrole ring cleavage in (VIII) upon treatment with hydroxylamine furnished aminopyridine (IX). Subsequent condensation with N-Boc-piperazine (X) provided adduct (XI). After acid cleavage of the Boc group of (XI), alkylation of the resulting piperazine with phenacyl chloride (XII) yielded the title compound. Alternatively, the title compound was obtained by condensation of chloride (IX) with N-phenacylpiperazine (XIII).