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【结 构 式】

【分子编号】52267

【品名】2-Ketoglutaric acid; 2-Oxoglutaric acid; alpha-Ketoglutaric acid; 2-Oxopentanedioic acid

【CA登记号】328-50-7

【 分 子 式 】C5H6O5

【 分 子 量 】146.09964

【元素组成】C 41.11% H 4.14% O 54.76%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

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

合成路线2

该中间体在本合成路线中的序号:(I)

 

1 Kuang H, Brown ML, Darries RR, et aL 1996. Enantioselective reductive amination of-keto acids to-amino acids by a pyridoxamine cafactor in a protein cavity. J Am Chem Soc, 118 (44): 10702~10706.
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) 52267 2-Ketoglutaric acid; 2-Oxoglutaric acid; alpha-Ketoglutaric acid; 2-Oxopentanedioic acid 328-50-7 C5H6O5 详情 详情
(II) 66460 2-(aminomethyl)-3-(hydroxymethyl)-6-methylphenol   C9H13NO2 详情 详情
Extended Information