SB-262470, NPS-2143
2-氯-6-[(2R)-3-[[1,1-二甲基-2-(2-萘基)乙基]氨基]-2-羟基丙氧基]苯腈 2-氯-6-[(2R)-3-[[1,1-二甲基-2-(2-萘基)乙基]氨基]-2-羟基丙氧基]苯腈盐酸盐 Chemical Name: 2-Chloro-6-[3-[1,1-dimethyl-2-(2-naphthyl)ethylamino]-2(R)-hydroxypropoxy]benzonitrile
CAS No. 284035-33-2, 324523-20-8 (monoHCl)
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator), NPS Pharmaceuticals (Originator)
合成路线:NPS-2143 can be obtained by coupling 2-chloro-6-[2(R)-oxiranylmethoxy]benzonitrile (I) with 1,1-dimethyl-2-(2-naphthyl)ethylamine (II) in ethanol at 50-60 C.Intermediates (I) and (II) can be obtained as follows:a) Treatment of 2-chloro-6-fluorobenzonitrile (III) with 18-crown-6 and potassium acetate in refluxing acetonitrile,followed by hydrolysis with NaOH in H2O provides 3-chloro-2-cyanophenol (IV),which is then condensed with 3-nitrobenzenesulfonic acid (2R)-2-oxiranylmethyl ester (V) in DMF by means of NaH to furnish 2-chloro-6-[2(R)-oxiranylmethoxy]benzonitrile (I).b) Treatment of 2-(aminomethyl)naphthalene (VI) with 2,4,6-triphenylpyrylium tetrafluoroborate in EtOH,followed by the reaction of the resulting compound dissolved in DMSO with the sodium salt obtained by treatment of 2-nitropropane (VII) with NaH in MeOH,gives the nitro derivative (VIII).Finally,reduction of the nitro group of (VIII) by hydrogenation over Ni Raney in EtOH yields 1,1,-dimethyl-2-(2-naphthyl)ethylamine (II).
📌 参考资料/链接：
参考文献标题:Method of using calcilytic cpds.
文献作者:Sheehan,D.; Del Mar,E.G.; Lago,M.A.; Southall,L.S.; Callahan,J.F.; Kotecha,N.R.; Thompson,M.; Barmore,R.M.; Keenan,R.M.; Van Wagenen,B.C.(GlaxoSmithKline Inc.; GlaxoSmithKline plc; NPS Pharmaceuticals,Inc.)
参考来源:US 6022894
📄 详细内容
合成路线:NPS-2143 can be obtained by coupling 2-chloro-6-[2(R)-oxiranylmethoxy]benzonitrile (I) with 1,1-dimethyl-2-(2-naphthyl)ethylamine (II) in ethanol at 50-60 C.Intermediates (I) and (II) can be obtained as follows:a) Treatment of 2-chloro-6-fluorobenzonitrile (III) with 18-crown-6 and potassium acetate in refluxing acetonitrile,followed by hydrolysis with NaOH in H2O provides 3-chloro-2-cyanophenol (IV),which is then condensed with 3-nitrobenzenesulfonic acid (2R)-2-oxiranylmethyl ester (V) in DMF by means of NaH to furnish 2-chloro-6-[2(R)-oxiranylmethoxy]benzonitrile (I).b) Treatment of 2-(aminomethyl)naphthalene (VI) with 2,4,6-triphenylpyrylium tetrafluoroborate in EtOH,followed by the reaction of the resulting compound dissolved in DMSO with the sodium salt obtained by treatment of 2-nitropropane (VII) with NaH in MeOH,gives the nitro derivative (VIII).Finally,reduction of the nitro group of (VIII) by hydrogenation over Ni Raney in EtOH yields 1,1,-dimethyl-2-(2-naphthyl)ethylamine (II).
参考文献标题:NPS-2143
文献作者:del Fresno,M.; Doggrell,S.A.; Castar,J.
参考来源:Drugs Fut 2002,27(2),140
产品链接: CAS No. 284035-33-2›› 产品链接: CAS No.324523-20-8››