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【结 构 式】 
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【分子编号】42920 【品名】5-methoxy-2-nitrophenylamine; 5-methoxy-2-nitroaniline 【CA登记号】16133-49-6 |
【 分 子 式 】C7H8N2O3 【 分 子 量 】168.1522 【元素组成】C 50% H 4.8% N 16.66% O 28.54% |
合成路线1
该中间体在本合成路线中的序号：(IV)The esterification of endo-8-methyl-8-azabicyclo[3,2,1]octan-3-ol (I) with trichloromethyl chloroformate (II) in acetonitrile gives the corresponding chloroformate (III), which is condensed with 5-methoxy-2-nitroaniline (IV) in pyridine, yielding the carbamate (V). The hydrogenation of the nitro group of (V) with H2 over Pd/C in methanol affords the expected amino derivative (VI). Finally, this compound is cyclized with trichloromethyl chloroformate (II) and Et3N in THF.
| 【1】 Turconi, M.; Schiantarelli, P.; Borsini, F.; Rizzi, C.A.; Ladinsky, H.; Donetti, A.; Azabicycloalkyl benzimidazolones: Interaction with serotonergic 5-HT3 and 5-HT4 receptors and potential therapeutic implications. Drugs Fut 1991, 16, 11, 1011. |
| 【2】 Turconi, M.; et al.; Synthesis of a new class of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid derivatives as highly potent 5-HT3 receptor antagonists. J Med Chem 1990, 33, 8, 2101. |
| 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) | 27768 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol | 120-29-6 | C8H15NO | 详情 | 详情 |
| (II) | 42918 | Chloroformic acid trichloromethyl ester; di-Phosgene; Chloroformic Acid, Trichloromethyl Ester; Trichloromethyl chloroformate; Diphosgene | 503-38-8 | C2Cl4O2 | 详情 | 详情 |
| (III) | 42919 | (1R,5S)-3-[(chlorocarbonyl)oxy]-8-methyl-8-azabicyclo[3.2.1]octane | C9H14ClNO2 | 详情 | 详情 | |
| (IV) | 42920 | 5-methoxy-2-nitrophenylamine; 5-methoxy-2-nitroaniline | 16133-49-6 | C7H8N2O3 | 详情 | 详情 |
| (V) | 42921 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 5-methoxy-2-nitrophenylcarbamate | C16H21N3O5 | 详情 | 详情 | |
| (VI) | 42922 | (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl 2-amino-5-methoxyphenylcarbamate | C16H23N3O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The intermediate phenylenediamine (VI) was prepared as follows. Reaction of 5-chloro-2-nitroaniline (I) with sodium methoxide afforded 5-methoxy-2-nitroaniline (II), which was subsequently converted to the N-Boc derivative (III). Methylation of (III) with iodomethane and NaH, followed by acidic treatment of the resulting N-methyl carbamate (IV), produced the N-methyl aniline (V). The nitro group of (V) was then reduced with the combination SnCl2-NaBH4 to furnish the diamine (VI).
| 【1】 Fujita, T.; Wada, K.; Oguchi, M.; Yanagisawa, H.; Fujimoto, K.; Fujiwara, T.; Horikoshi, H.; Yoshioka, T. (Sankyo Co., Ltd.); Benzimidazole derivs., their preparation and their therapeutic use. CA 2177858; EP 0745600; JP 1997295970; JP 2000001487; US 5886014 . |
| 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) | 15709 | 5-chloro-2-nitrophenylamine; 5-chloro-2-nitroaniline | 1635-61-6 | C6H5ClN2O2 | 详情 | 详情 |
| (II) | 42920 | 5-methoxy-2-nitrophenylamine; 5-methoxy-2-nitroaniline | 16133-49-6 | C7H8N2O3 | 详情 | 详情 |
| (III) | 46874 | tert-butyl 5-methoxy-2-nitrophenylcarbamate | C12H16N2O5 | 详情 | 详情 | |
| (IV) | 46875 | tert-butyl 5-methoxy-2-nitrophenyl(methyl)carbamate | C13H18N2O5 | 详情 | 详情 | |
| (V) | 46876 | 5-methoxy-N-methyl-2-nitroaniline; N-(5-methoxy-2-nitrophenyl)-N-methylamine | C8H10N2O3 | 详情 | 详情 | |
| (VI) | 46877 | N-(2-amino-5-methoxyphenyl)-N-methylamine; 4-methoxy-N(2)-methyl-1,2-benzenediamine | C8H12N2O | 详情 | 详情 |