【结 构 式】 |
【分子编号】38163 【品名】ethyl 5-nitro-1H-indole-2-carboxylate 【CA登记号】16732-57-3 |
【 分 子 式 】C11H10N2O4 【 分 子 量 】234.21148 【元素组成】C 56.41% H 4.3% N 11.96% O 27.32% |
合成路线1
该中间体在本合成路线中的序号:(I)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).
【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:(III)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.
【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 |