新产品编号:294761
Chemical Name: 2-[4-[2-[4-(6-Aminopyridin-2-yl)phenyl]ethyl]piperazin-1-yl]-1-phenylethanone
CAS No. 198211-96-0
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线: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).
📌 参考资料/链接：
参考文献标题:6-Phenylpyridyl-2-amine derivs.
文献作者:Lowe,J.A.III; Whittle,P.J.(Pfizer Inc.)
参考来源:EP 0891332; JP 1999510513; WO 9736871
📄 详细内容
合成路线: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).
参考文献标题:A new class of selective and potent inhibitors of neuronal nitric oxide synthase
文献作者: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.
参考来源:Bioorg Med Chem Lett 1999,9(17),2569
产品链接: CAS No. 198211-96-0››