【结 构 式】 |
【分子编号】52866 【品名】2-[2-fluoro(3-methoxyphenyl)anilino]-2-oxoacetyl chloride 【CA登记号】 |
【 分 子 式 】C15H11ClFNO3 【 分 子 量 】307.7083832 【元素组成】C 58.55% H 3.6% Cl 11.52% F 6.17% N 4.55% O 15.6% |
合成路线1
该中间体在本合成路线中的序号:(II)The isatin derivative (III) was prepared by acylation of diarylamine (I) with oxalyl chloride, followed by intramolecular cyclization of the intermediate (II) under Friedel-Crafts reaction conditions. Treatment of (III) with hydroxylamine led to formation of the oxime (IV), which was further reduced to amine (V) by catalytic hydrogenation over Pd/C. After protection of amine (V) as the benzyl carbamate (VI), alkylation with iodomethane in the presence of K2CO3 produced the 3-methyl oxindole (VII). Removal of the N-carbobenzoxy group of (VII) was achieved by catalytic hydrogenation over Pd/C to yield the deprotected amine, which was resolved by means of dibenzoyl-L-tartaric acid. The target (S)-amine (VIII) was finally acylated with beta-carboline-3-carbonyl chloride (IX) to furnish the title amide.
【1】 Yamada, K.; Hikota, M.; Yura, T.; Shikano, T.; Nagasaki, M. (Tanabe Seiyaku Co., Ltd.); Beta-carboline derivs. with anticholecystoquinine activity. EP 0572235; JP 1994041126; US 5434148 . |
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) | 52865 | N-(2-fluorophenyl)-N-(3-methoxyphenyl)amine; 2-fluoro-N-(3-methoxyphenyl)aniline | C13H12FNO | 详情 | 详情 | |
(II) | 52866 | 2-[2-fluoro(3-methoxyphenyl)anilino]-2-oxoacetyl chloride | C15H11ClFNO3 | 详情 | 详情 | |
(III) | 52867 | 1-(2-fluorophenyl)-6-methoxy-1H-indole-2,3-dione | C15H10FNO3 | 详情 | 详情 | |
(IV) | 52868 | 1-(2-fluorophenyl)-6-methoxy-1H-indole-2,3-dione 3-oxime | C15H11FN2O3 | 详情 | 详情 | |
(V) | 52869 | 3-amino-1-(2-fluorophenyl)-6-methoxy-1,3-dihydro-2H-indol-2-one | C15H13FN2O2 | 详情 | 详情 | |
(VI) | 52870 | benzyl 1-(2-fluorophenyl)-6-methoxy-2-oxo-2,3-dihydro-1H-indol-3-ylcarbamate | C23H19FN2O4 | 详情 | 详情 | |
(VII) | 52871 | benzyl 1-(2-fluorophenyl)-6-methoxy-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-ylcarbamate | C24H21FN2O4 | 详情 | 详情 | |
(VIII) | 52872 | (3S)-3-amino-1-(2-fluorophenyl)-6-methoxy-3-methyl-1,3-dihydro-2H-indol-2-one | C16H15FN2O2 | 详情 | 详情 | |
(IX) | 52873 | 9H-beta-carboline-3-carbonyl chloride | C12H7ClN2O | 详情 | 详情 |