【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% |
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 |