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【结 构 式】

【分子编号】69280

【品名】(1S,2S,4S)-1-benzyl 2-methyl 4-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)cyclopentane-1,2-dicarboxylate

【CA登记号】 

【 分 子 式 】C32H34N2O6S

【 分 子 量 】574.698

【元素组成】C 66.88% H 5.96% N 4.87% O 16.70% S 5.58%

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:(XIX)

Condensation of the cyclopentanol derivative (XV) with the quinolinol derivative (XI) under Mitsunobu conditions (PPh3, DIAD) in toluene affords adduct (XVI). Methyl ester (XVI) is hydrolyzed with LiOH.H2O in THF/H2O, giving the carboxylate lithium salt (XV), which upon coupling with ethyl 1(R)-amino-2(S)-vinylcyclopropanecarboxylate (IX) in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) in THF/H2O yields the desired intermediate (I) .
Intermediate (XVI) can also be prepared by condensation of quinolinol derivative (XI) with a different cyclopentanol derivative (XVIII) under Mitsunobu conditions (PPh3, DIAD) in toluene/THF. The benzyl ester in the resulting adduct (XIX) is converted to the corresponding carboxylic acid (XX) by treatment with triethylsilane and Pd(OAc)2 in refluxing THF or Me-THF. Finally, acid (XX) is amidated with N-methylhex-5-enamine (VII) in the presence of EEDQ in Me-THF or THF/Me-THF at 50 °C .

1 Horvath, A., Depre, D.P.M., Ormerod, D.J. (Tibotec Pharmaceuticals Ltd.). Processes and intermediates for preparing a macrocyclic protease inhibitor of HCV. WO 2008092955.
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) 69263 (1S,2R)-ethyl 1-((1S,2S,4S)-2-(hex-5-en-1-yl(methyl)carbamoyl)-4-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)cyclopentanecarboxamido)-2-vinylcyclopropanecarboxylate   C39H50N4O6S 详情 详情
(VII) 69268 N-methylhex-5-enamine;N-methylhex-5-en-1-amine   C7H15N 详情 详情
(IX) 69270 (1R,2S)-ethyl 1-amino-2-vinylcyclopropanecarboxylate 746657-36-3 C8H13NO2 详情 详情
(XI) 69272 7-methoxy-8-methyl-2-[4-(1-methylethyl)-2-thiazolyl]-2-4-Quinolinol;(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-ol 923289-21-8 C17H18N2O2S 详情 详情
(XV) 69276 (1S,2S,4S)-methyl 2-(hex-5-en-1-yl(methyl)carbamoyl)-4-hydroxycyclopentanecarboxylate   C15H25NO4 详情 详情
(XVI) 69277 (1S,2S,4S)-methyl 2-(hex-5-en-1-yl(methyl)carbamoyl)-4-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)cyclopentanecarboxylate   C32H41N3O5S 详情 详情
(XVII) 69278 lithium (1S,2S,4S)-2-(hex-5-en-1-yl(methyl)carbamoyl)-4-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)cyclopentanecarboxylate   C31H38LiN3O5S 详情 详情
(XVIII) 69279 (1S,2S,4S)-1-benzyl 2-methyl 4-hydroxycyclopentane-1,2-dicarboxylate   C15H18O5 详情 详情
(XIX) 69280 (1S,2S,4S)-1-benzyl 2-methyl 4-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)cyclopentane-1,2-dicarboxylate   C32H34N2O6S 详情 详情
(XX) 69281 (1S,2S,4S)-4-((2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yl)oxy)-2-(methoxycarbonyl)cyclopentanecarboxylic acid   C25H28N2O6S 详情 详情
Extended Information