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【结 构 式】

【分子编号】69060

【品名】 

【CA登记号】 

【 分 子 式 】C38H51N5O9S

【 分 子 量 】753.917

【元素组成】C 60.54% H 6.82% N 9.29% O 20.10% S 4.25%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(V)

In one method, intramolecular ring-closing metathesis of diene (I) using Neolyst-M1 or Zhan 1B catalysts in CH2Cl2 produces the macrocyclic triamide (II), which undergoes methyl ester hydrolysis with LiOH in THF/H2O at 40 °C, giving carboxylic acid (III). Subsequent coupling of acid (III) with the vinylcyclopropylamine derivative (IV) in the presence of HATU, DMAP and DIEA in CH2Cl2 at 40 °C yields the corresponding amide (V), which is finally reduced by catalytic hydrogenation over Pd/C in EtOAc .
In an alternative strategy, reduction of the macrocyclic alkene (II) by means of H2 and Pd/C in EtOAc yields the saturated macrocycle (VI), which by hydrolysis with LiOH in THF/MeOH/H2O furnishes carboxylic acid (VII). Finally, macrocyclic free acid (VII) is condensed with the ethylcyclopropylamine derivative (VIII) by means of HATU, DMAP and DIEA in DMF .

1 Holloway, M.K., Liverton, N.J., Ludmerer, S.W. et al. (Merck & Co., Inc.). HCV NS3 protease inhibitors. EP 1910404, EP 924593, JP 2009502793, US 2007027071, WO 2007015787, WO 2007015855.
2 McCauley, J.A., McIntyre, C.J., Rudd, M.T. et al. Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor. J Med Chem 2010, 53(6): 2443-63.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 69055 (3S,5R)-1-(2-((((2,2-dimethylhex-5-en-1-yl)oxy)carbonyl)amino)-3,3-dimethylbutanoyl)-5-(methoxycarbonyl)pyrrolidin-3-yl 4-vinylisoindoline-2-carboxylate   C32H45N3O7 详情 详情
(II) 69056     C30H41N3O7 详情 详情
(III) 69057     C29H39N3O7 详情 详情
(IV) 69058 (1S,2R)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide hydrochloride   C9H14N2O3S.HCl 详情 详情
(V) 69060     C38H51N5O9S 详情 详情
(VI) 69061     C30H43N3O7 详情 详情
(VII) 69062     C29H39N3O7 详情 详情
(VIII) 69059 (1S,2S)-1-amino-N-(cyclopropylsulfonyl)-2-ethylcyclopropanecarboxamide hydrochloride   C9H16N2O3S.HCl 详情 详情
Extended Information