【结 构 式】 |
【分子编号】52271 【品名】ethyl 3-{2-(dimethylamino)-1-[(ethyloxy)carbonyl]ethenyl}-5-fluoro-1-methyl-1H-indole-2-carboxylate 【CA登记号】 |
【 分 子 式 】C19H23FN2O4 【 分 子 量 】362.4011032 【元素组成】C 62.97% H 6.4% F 5.24% N 7.73% O 17.66% |
合成路线1
该中间体在本合成路线中的序号:(VI)Condensation between 4-fluorophenylhydrazine (I) and 2-ketoglutaric acid (II) produced the intermediate hydrazone (III), which was cyclized and esterified to the indole diester (IV) under Fischer synthesis conditions. Alkylation of the indole nitrogen with iodomethane and NaH produced the N-methyl indole (V). This was condensed with dimethylformamide-dimethylacetal in refluxing DMF to furnish the enamino ester (VI). Condensation of enamine (VI) with aniline (VII), followed by cyclization of the intermediate enamino ester under basic conditions, gave rise to the pyridoindole (VIII). The remaining ester group of (VIII) was then hydrolyzed with NaOH to the corresponding carboxylic acid (IX), which was finally coupled with pyrrolidine (X) via activation with carbonyldiimidazole.
【1】 Sevrin, M.; Maloizel, C.; Evanno, Y.; Legalloudec, O.; George, P. (Sanofi-Synthelabo); 1H-Pyrido[3,4-b]indole-4-carboxamide derivs., preparation and application thereof in therapeutics. FR 2754262; JP 2001508403; US 6075021; WO 9815552 . |
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) | 22135 | 1-(4-fluorophenyl)hydrazine | 371-14-2 | C6H7FN2 | 详情 | 详情 |
(II) | 52267 | 2-Ketoglutaric acid; 2-Oxoglutaric acid; alpha-Ketoglutaric acid; 2-Oxopentanedioic acid | 328-50-7 | C5H6O5 | 详情 | 详情 |
(III) | 52268 | 2-[2-(4-fluorophenyl)hydrazono]pentanedioic acid | C11H11FN2O4 | 详情 | 详情 | |
(IV) | 52269 | ethyl 3-[2-(ethyloxy)-2-oxoethyl]-5-fluoro-1H-indole-2-carboxylate | C15H16FNO4 | 详情 | 详情 | |
(V) | 52270 | ethyl 3-[2-(ethyloxy)-2-oxoethyl]-5-fluoro-1-methyl-1H-indole-2-carboxylate | C16H18FNO4 | 详情 | 详情 | |
(VI) | 52271 | ethyl 3-{2-(dimethylamino)-1-[(ethyloxy)carbonyl]ethenyl}-5-fluoro-1-methyl-1H-indole-2-carboxylate | C19H23FN2O4 | 详情 | 详情 | |
(VII) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
(VIII) | 52272 | ethyl 6-fluoro-9-methyl-1-oxo-2-phenyl-2,9-dihydro-1H-beta-carboline-4-carboxylate | C21H17FN2O3 | 详情 | 详情 | |
(IX) | 52273 | 6-fluoro-9-methyl-1-oxo-2-phenyl-2,9-dihydro-1H-beta-carboline-4-carboxylic acid | C19H13FN2O3 | 详情 | 详情 | |
(X) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |