methyl 6-[(5-amino-1-benzofuran-2-yl)carbonyl]-8-(chloromethyl)-4-hydroxy-2-methyl-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】63443

【品名】methyl 6-[(5-amino-1-benzofuran-2-yl)carbonyl]-8-(chloromethyl)-4-hydroxy-2-methyl-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate

【CA登记号】

【分子式】C₂₃H₂₀ClN₃O₅

【分子量】453.88172

【元素组成】C 60.86% H 4.44% Cl 7.81% N 9.26% O 17.63%

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：(VII)

5-Nitrobenzofuran-2-carboxylic acid (I) is coupled to 4-nitrophenol (II) in the presence of EDC to produce the p-nitrophenyl ester (III). Subsequent acylation of the duocarmycin derivative (IV) with active ester (III) leads to amide (V). Cyclopropane ring opening in (V) with HCl in DMF furnishes the chloromethyl derivative (VI). The nitro group of (VI) is then reduced by catalytic hydrogenation, yielding amine (VII). Acylation of (VII) with 7-nitroindole-2-carboxylic acid (VIII) affords the corresponding amide (IX)

参考文献中间体

合成目标

【1】 McGee, D.P.C.; Saunders, O.L.; Martichonok, V.; Wu, G.; Ng, H.P.; Li, Z.; Yarranton, G.T. (Medarex, Inc.); Cytotoxic agents. US 2003050331; WO 0296910 .

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)	63365	5-nitro-1-benzofuran-2-carboxylic acid	10242-12-3	C₉H₅NO₅	详情	详情
(II)	11236	4-Nitrophenol; p-Nitrophenol	100-02-7	C₆H₅NO₃	详情	详情
(III)	63440	4-nitrophenyl 5-nitro-1-benzofuran-2-carboxylate		C₁₅H₈N₂O₇	详情	详情
(IV)	38365	methyl (3bR,4aS)-2-methyl-8-oxo-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate		C₁₄H₁₄N₂O₃	详情	详情
(V)	63441	methyl 2-methyl-6-[(5-nitro-1-benzofuran-2-yl)carbonyl]-8-oxo-1,4,4a,5,6,8-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-3-carboxylate		C₂₃H₁₇N₃O₇	详情	详情
(VI)	63442	methyl 8-(chloromethyl)-4-hydroxy-2-methyl-6-[(5-nitro-1-benzofuran-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate		C₂₃H₁₈ClN₃O₇	详情	详情
(VII)	63443	methyl 6-[(5-amino-1-benzofuran-2-yl)carbonyl]-8-(chloromethyl)-4-hydroxy-2-methyl-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate		C₂₃H₂₀ClN₃O₅	详情	详情
(VIII)	63444	7-nitro-1H-indole-2-carboxylic acid		C₉H₆N₂O₄	详情	详情
(IX)	63445	methyl 8-(chloromethyl)-4-hydroxy-2-methyl-6-[(5-{[(7-nitro-1H-indol-2-yl)carbonyl]amino}-1-benzofuran-2-yl)carbonyl]-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-1-carboxylate		C₃₂H₂₄ClN₅O₈	详情	详情

Extended Information