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【结 构 式】 
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【分子编号】30195 【品名】benzyl 3-[[(1-methyl-1H-pyrrol-3-yl)carbonyl]amino]propanoate 【CA登记号】 |
【 分 子 式 】C16H18N2O3 【 分 子 量 】286.3306 【元素组成】C 67.12% H 6.34% N 9.78% O 16.76% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of 1-methylpyrole-3-carboxylic acid (I) with beta-alanine benzyl ester (II) by means of diethyl phosphorocyanidate (PCA) in DMF gives the corresponding amide (III), which is debenzylated with H2 over Pd/C in THF yielding the substituted beta-alanine (IV). The cyclization of (IV) by means of polyphosphoric acid (PPA) at 100 C affords the pyrroloazepine (V), which is alkylated with 1-bromo-3-chloropropane (VI) and potassium tert-butoxide in THF giving the 3-chloropropyl derivative (VII). The condensation of (VII) with 1-(4-fluorophenyl)piperazine (VIII) by means of K2CO3 and NaI in refluxing acetonitrile yields the expected addition product (IX), which is selectively reduced at the 8-position with NaBH4 in ethanol affording the 8-hydroxy derivative (X) as a racemic mixture. Finally, this compound is submitted to optical resolution by chiral chromatography providing the target chiral compound.
| 【1】 Shibata, M.; Ogata, A.; Hayashi, Y.; Kamei, T.; Mizuno, A.; Shimamoto, T.; Takiguchi, C.; Inomata, N.; Nakanishi, K.; Oka, N.; Synthesis and serotonin 2 (5-HT2) receptor antagonist activity of 5-aminoalkyl-substituted pyrrolo [3,2-c]azepines and related compounds. Chem Pharm Bull 2000, 48, 5, 623. |
| 【2】 Mizuno, A.; Shibata, M.; Iwamori, T.; Shimamoto, T.; Nakanishi, K.; Inomata, N. (Suntory Ltd.); Pyrroloazepine derivs.. EP 0807632; US 5962448; WO 9720845 . |
| 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) | 30193 | 1-methyl-1H-pyrrole-3-carboxylic acid | C6H7NO2 | 详情 | 详情 | |
| (II) | 30194 | benzyl 3-aminopropanoate | 27019-47-2 | C10H13NO2 | 详情 | 详情 |
| (III) | 30195 | benzyl 3-[[(1-methyl-1H-pyrrol-3-yl)carbonyl]amino]propanoate | C16H18N2O3 | 详情 | 详情 | |
| (IV) | 30196 | N-[(1-methyl-1H-pyrrol-3-yl)carbonyl]-beta-alanine | C9H12N2O3 | 详情 | 详情 | |
| (V) | 30197 | 1-methyl-6,7-dihydropyrrolo[3,2-c]azepine-4,8(1H,5H)-dione | C9H10N2O2 | 详情 | 详情 | |
| (VI) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (VII) | 30198 | 5-(3-chloropropyl)-1-methyl-6,7-dihydropyrrolo[3,2-c]azepine-4,8(1H,5H)-dione | C12H15ClN2O2 | 详情 | 详情 | |
| (VIII) | 12143 | 1-(4-Fluorophenyl)piperazine | 2252-63-3 | C10H13FN2 | 详情 | 详情 |
| (IX) | 30199 | 5-[3-[4-(4-fluorophenyl)-1-piperazinyl]propyl]-1-methyl-6,7-dihydropyrrolo[3,2-c]azepine-4,8(1H,5H)-dione | C22H27FN4O2 | 详情 | 详情 | |
| (X) | 30200 | 5-[3-[4-(4-fluorophenyl)-1-piperazinyl]propyl]-8-hydroxy-1-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one | C22H29FN4O2 | 详情 | 详情 |