ethyl 5-amino-1H-indole-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】38164

【品名】ethyl 5-amino-1H-indole-2-carboxylate

【CA登记号】

【分子式】C₁₁H₁₂N₂O₂

【分子量】204.22856

【元素组成】C 64.69% H 5.92% N 13.72% O 15.67%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

Ethyl 5-nitroindole-2-carboxylate (I) was hydrogenated over Pd/C to give amino indole (II), which was condensed with methanesulfonyl chloride, affording sulfonamide (III). Subsequent hydrolysis of the ester group of (III) furnished the intermediate indolecarboxylic acid (IV).

参考文献中间体

合成目标

【1】 Romero, D.L.; Thomas, R.C.; May, P.D.; Poel, T.-J. (Pharmacia Corp.); Alkyl substd. piperadinyl and piperazinyl anti-AIDS cpds.. EP 0797576; JP 1998510530; US 5866589; WO 9618628 .

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)	38163	ethyl 5-nitro-1H-indole-2-carboxylate	16732-57-3	C₁₁H₁₀N₂O₄	详情	详情
(II)	38164	ethyl 5-amino-1H-indole-2-carboxylate		C₁₁H₁₂N₂O₂	详情	详情
(III)	38165	ethyl 5-[(methylsulfonyl)amino]-1H-indole-2-carboxylate		C₁₂H₁₄N₂O₄S	详情	详情
(IV)	38166	5-[(methylsulfonyl)amino]-1H-indole-2-carboxylic acid		C₁₀H₁₀N₂O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Treatment of the cyclopropabenzindole derivative (CBI) (I) with hydrochloric acid in ethyl acetate affords the chloromethyl derivative (II). The final step is the condensation of (II) with the acid (VIII) by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) in DMF. The acid (VIII) was prepared as follows: Ethyl 5-nitroindole-2-carboxylate (III) is reductively transformed to its corresponding amine (IV) by hydrogenation over Pd/C. The amine (IV) is then converted to its acetamido ester (V) by treatment with acetic anhydride in ethyl acetate. Ester (V) is then hydrolyzed using NaOH to afford the corresponding acid (VI), which is coupled to amine (IV) in the presence of EDCI to yield ester (VII). Finally (VII) is converted to acid (VIII) by treatment with NaOH.

参考文献中间体

合成目标

【1】 Wang, Y.; Ye, W.; Wright, S.C.; Larrick, J.W.; Wang, H.; Yuan, H.; Synthesis and preliminary biological evaluations of CC-1065 analogues: Effects of different linkers terminal amides on biological activity. J Med Chem 2000, 43, 8, 1541.
【2】 Larrick, J.W.; Wright, S.C.; Wang, Y. (Panorama Research, Inc.); DNA-binding indole derivs., their prodrugs and immunoconjugates as anticancer agents. WO 9744000 .

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)	40977	1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol		C₁₃H₁₂ClNO	详情	详情
(II)	40978	1,2,2a,3,9,9a-hexahydro-4H-benzo[e]cyclopropa[c]indol-4-one		C₁₃H₁₃NO	详情	详情
(III)	38163	ethyl 5-nitro-1H-indole-2-carboxylate	16732-57-3	C₁₁H₁₀N₂O₄	详情	详情
(IV)	38164	ethyl 5-amino-1H-indole-2-carboxylate		C₁₁H₁₂N₂O₂	详情	详情
(V)	40973	ethyl 5-(acetamido)-1H-indole-2-carboxylate		C₁₃H₁₄N₂O₃	详情	详情
(VI)	40974	5-(acetamido)-1H-indole-2-carboxylic acid		C₁₁H₁₀N₂O₃	详情	详情
(VII)	40975	ethyl 5-([[5-(acetamido)-1H-indol-2-yl]carbonyl]amino)-1H-indole-2-carboxylate		C₂₂H₂₀N₄O₄	详情	详情
(VIII)	40976	5-([[5-(acetamido)-1H-indol-2-yl]carbonyl]amino)-1H-indole-2-carboxylic acid		C₂₀H₁₆N₄O₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Coupling between ethyl 5-aminoindole-2-carboxylate (I) and 5-nitrobenzofuran-2-carboxylic acid (II) by means of HBTU affords amide (III). Subsequent ethyl ester hydrolysis under alkaline conditions yields the carboxylic acid (IV). Ring opening of the cyclopropane-fused compound (V) with anhydrous HCl in EtOAc leads to the chloromethyl compound (VI). Acid (IV) is finally coupled to amine (VI) in the presence of EDC to furnish the title compound.

参考文献中间体

合成目标

【1】 Wang, Y.; Li, L.; Ye, W.; Tian, Z.; Jiang, W.; Wang, H.; Wright, S.C.; Larrick, J.W.; CC-1065 analogues bearing different DNA-binding subunits: Synthesis, antitumor activity, and preliminary toxicity study. J Med Chem 2003, 46, 4, 634.

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)	38164	ethyl 5-amino-1H-indole-2-carboxylate		C₁₁H₁₂N₂O₂	详情	详情
(II)	63365	5-nitro-1-benzofuran-2-carboxylic acid	10242-12-3	C₉H₅NO₅	详情	详情
(III)	63366	ethyl 5-{[(5-nitro-1-benzofuran-2-yl)carbonyl]amino}-1H-indole-2-carboxylate		C₂₀H₁₅N₃O₆	详情	详情
(IV)	63367	5-{[(5-nitro-1-benzofuran-2-yl)carbonyl]amino}-1H-indole-2-carboxylic acid		C₁₈H₁₁N₃O₆	详情	详情
(V)	40978	1,2,2a,3,9,9a-hexahydro-4H-benzo[e]cyclopropa[c]indol-4-one		C₁₃H₁₃NO	详情	详情
(VI)	40977	1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol		C₁₃H₁₂ClNO	详情	详情

Extended Information