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【结 构 式】 
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【分子编号】46498 【品名】4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]-1-butanamine; 4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]butylamine 【CA登记号】 |
【 分 子 式 】C16H24N2O2 【 分 子 量 】276.37884 【元素组成】C 69.53% H 8.75% N 10.14% O 11.58% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Cycloaddition of the azomethine ylide resulting from N-trimethylsilylmethyl-N-methoxymethyl-(R)-alpha-methylbenzylamine (II) to 5-methoxycoumarin (I) produced the chiral cis-benzopyranopyrrole system (III). Lactone reduction by means of LiAlH4 or LiBH4 afforded diol (IV). After conversion of the primary alcohol of (IV) to either the corresponding chloride or the mesylate, cyclization in the presence of potassium tert-butoxide generated the tricyclic compound (V). The alpha-methylbenzyl group of (V) was removed by catalytic hydrogenation to give amine (VI), which was alkylated with 4-bromobutyronitrile yielding (VII). Reduction of the cyano group of (VII) using LiAlH4 in the presence AlCl3 or by catalytic hydrogenation in the presence of Raney-Ni produced the primary amine (VIII).
| 【1】 Meyer, M.D.; Altenbach, R.J.; Basha, F.; Carroll, W.A.; Drizin, I.; Kerwin, J.F.; Wendt, M.D.; Haight, A.R.; Zhang, W. (Abbott Laboratories Inc.); Benzopyranopyrrole and benzopyranopyridine alpha-1 adrenergic cpds.. EP 0942911; US 5891882; US 6046207; WO 9824791 . |
| 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) | 46491 | 5-methoxy-2H-chromen-2-one | C10H8O3 | 详情 | 详情 | |
| (II) | 46492 | (1R)-N-(methoxymethyl)-1-phenyl-N-[(trimethylsilyl)methyl]-1-ethanamine; N-(methoxymethyl)-N-[(1R)-1-phenylethyl]-N-[(trimethylsilyl)methyl]amine | C14H25NOSi | 详情 | 详情 | |
| (III) | 46493 | (3aR,9bR)-9-methoxy-2-[(1R)-1-phenylethyl]-2,3,3a,9b-tetrahydrochromeno[3,4-c]pyrrol-4(1H)-one | C20H21NO3 | 详情 | 详情 | |
| (IV) | 46494 | 2-[(3R,4R)-4-(hydroxymethyl)-1-[(1R)-1-phenylethyl]pyrrolidinyl]-3-methoxyphenol | C20H25NO3 | 详情 | 详情 | |
| (V) | 46495 | (3aR,9bR)-9-methoxy-2-[(1R)-1-phenylethyl]-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole; (3aR,9bR)-2-[(1R)-1-phenylethyl]-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrol-9-yl methyl ether | C20H23NO2 | 详情 | 详情 | |
| (VI) | 46496 | (3aR,9bR)-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrol-9-yl methyl ether; (3aR,9bR)-9-methoxy-1,2,3,3a,4,9b-hexahydrochromeno[3,4-c]pyrrole | C12H15NO2 | 详情 | 详情 | |
| (VII) | 46497 | 4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]butanenitrile | C16H20N2O2 | 详情 | 详情 | |
| (VIII) | 46498 | 4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]-1-butanamine; 4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]butylamine | C16H24N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)The amino ester intermediate (XIII) was treated with phosgene and Et3N, and to the resulting isocyanate (XXVI) was added the primary amine (VIII), producing urea (XXVII). Then, cyclization of (XXVII) in refluxing toluene generated the desired compound, which was isolated as the hydrochloride salt.
| 【1】 Meyer, M.D.; Altenbach, R.J.; Basha, F.; Carroll, W.A.; Drizin, I.; Kerwin, J.F.; Wendt, M.D.; Haight, A.R.; Zhang, W. (Abbott Laboratories Inc.); Benzopyranopyrrole and benzopyranopyridine alpha-1 adrenergic cpds.. EP 0942911; US 5891882; US 6046207; WO 9824791 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 46498 | 4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]-1-butanamine; 4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]butylamine | C16H24N2O2 | 详情 | 详情 | |
| (XIII) | 46503 | methyl 7-amino-2-phenylthieno[2,3-b]pyrazine-6-carboxylate | C14H11N3O2S | 详情 | 详情 | |
| (XXVI) | 46513 | methyl 7-isocyanato-2-phenylthieno[2,3-b]pyrazine-6-carboxylate | C15H9N3O3S | 详情 | 详情 | |
| (XXVII) | 46514 | methyl 7-[[([4-[(3aR,9bR)-9-methoxy-1,3a,4,9b-tetrahydrochromeno[3,4-c]pyrrol-2(3H)-yl]butyl]amino)carbonyl]amino]-2-phenylthieno[2,3-b]pyrazine-6-carboxylate | C31H33N5O5S | 详情 | 详情 |