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【结 构 式】

【分子编号】41137

【品名】N-[2-[2-(acetamido)ethyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]-4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamide

【CA登记号】

【 分 子 式 】C27H26F3N3O2

【 分 子 量 】481.5176696

【元素组成】C 67.35% H 5.44% F 11.84% N 8.73% O 6.65%

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:(XII)

Condensation of 2-chloro-4-nitrobenzoic acid (I) with dimethyl malonate produced the arylmalonate (II). This was subjected to hydrolysis and subsequent decarboxylation to afford diacid (III). Conversion of (III) to the cyclic anhydride (IV) upon refluxing with Ac2O, and then reduction with borane in THF gave rise to diol (V). Optionally, diol (V) was obtained by direct reduction of diacid (III) with borane. Nitro diol (V) was reduced to amine (VI) by hydrogenation over Pt/C. This was condensed with acid chloride (VIII) (prepared from carboxylic acid (VII) and SOCl2) to afford amide (IX). After conversion to dimesylate (X), cyclization with N-acetyl ethylenediamine (XI) furnished the tetrahydroisoquinoline (XII). Acidic hydrolysis of the acetamido group of (XIV) gave primary amine (XIII) which was finally treated with methyl chloroformate to furnish the title carbamate.

1 Chang, G.; Quallich, G.J. (Pfizer Inc.); Apo B-secretion/MTP inhibitory amides. EP 0944602; JP 2000505810; WO 9823593 .
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) 41126 2-chloro-4-nitrobenzoic acid 99-60-5 C7H4ClNO4 详情 详情
(II) 41127 2-[2-methoxy-1-(methoxycarbonyl)-2-oxoethyl]-4-nitrobenzoic acid C12H11NO8 详情 详情
(III) 41128 2-(carboxymethyl)-4-nitrobenzoic acid C9H7NO6 详情 详情
(IV) 41129 6-nitro-1H-isochromene-1,3(4H)-dione C9H5NO5 详情 详情
(V) 41130 2-[2-(hydroxymethyl)-5-nitrophenyl]-1-ethanol C9H11NO4 详情 详情
(VI) 41131 2-[5-amino-2-(hydroxymethyl)phenyl]-1-ethanol C9H13NO2 详情 详情
(VII) 41132 4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxylic acid C14H9F3O2 详情 详情
(VIII) 41133 4'-(trifluoromethyl)[1,1'-biphenyl]-2-carbonyl chloride C14H8ClF3O 详情 详情
(IX) 41134 N-[3-(2-hydroxyethyl)-4-(hydroxymethyl)phenyl]-4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamide C23H20F3NO3 详情 详情
(X) 41135 2-[[(methylsulfonyl)oxy]methyl]-5-([[4'-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino)phenethyl methanesulfonate C25H24F3NO7S2 详情 详情
(XI) 41136 N-(2-aminoethyl)acetamide 1001-53-2 C4H10N2O 详情 详情
(XII) 41137 N-[2-[2-(acetamido)ethyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]-4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamide C27H26F3N3O2 详情 详情
(XIII) 41138 N-[2-(2-aminoethyl)-1,2,3,4-tetrahydro-6-isoquinolinyl]-4'-(trifluoromethyl)[1,1'-biphenyl]-2-carboxamide C25H24F3N3O 详情 详情
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