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【结 构 式】 
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【分子编号】50061 【品名】(3R,4R)-4-bromo-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-yl (2R)-2-methoxy-2-phenylethanoate 【CA登记号】 |
【 分 子 式 】C26H26BrNO4 【 分 子 量 】496.40078 【元素组成】C 62.91% H 5.28% Br 16.1% N 2.82% O 12.89% |
合成路线1
该中间体在本合成路线中的序号：(XV)Electrophilic bromination of chromene (XII) with N-bromosuccinimide in moist DMSO produced the trans-bromohydrin (XIII). The racemic (XIII) was then resolved by esterification with (R)-alpha-methoxyphenylacetic acid (XIV), using DCC as the coupling reagent, and subsequent chromatographic separation of the diastereomeric mixture. Hydrolysis of the desired bromoester isomer (XV) under basic conditions gave rise to the chiral cis-epoxide (XVI). The target amino alcohol (XVII) was then obtained by regioselective ring opening of epoxide (XVI) with ethanolic ammonia in a pressure vessel. Finally, coupling of (XVII) with nicotinoyl chloride (XVIII) furnished the title amide.
| 【1】 Manley, P.W. (Novartis AG; Novartis Deutschland GmbH); 2,2-Dialkyl- and 2,2-dialkyl-3, 4-dihydro-3-hydroxy-2H-1-benzopyrans, their use as pharmaceuticals. EP 0623129; WO 9412493 . |
| 【2】 Manley, P.W. (Novartis AG); 2,2-Dialkyl- and 2,2-dialkyl-3, 4-dihydro-3-hydroxy-2H-1-benzopyrans. US 5574049 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 50058 | 4-(2,2-dimethyl-2H-chromen-6-yl)-2-methylpyridine | C17H17NO | 详情 | 详情 | |
| (XIII) | 50059 | (3R,4R)-4-bromo-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-ol | C17H18BrNO2 | 详情 | 详情 | |
| (XIV) | 50060 | (2R)-2-methoxy-2-phenylethanoic acid | 3966-32-3 | C9H10O3 | 详情 | 详情 |
| (XV) | 50061 | (3R,4R)-4-bromo-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-yl (2R)-2-methoxy-2-phenylethanoate | C26H26BrNO4 | 详情 | 详情 | |
| (XVI) | 50062 | 4-[(1aS,7bS)-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl]-2-methylpyridine | C17H17NO2 | 详情 | 详情 | |
| (XVII) | 50063 | (3S,4R)-4-amino-2,2-dimethyl-6-(2-methyl-4-pyridinyl)-3,4-dihydro-2H-chromen-3-ol | C17H20N2O2 | 详情 | 详情 | |
| (XVIII) | 10753 | Nicotinoyl chloride | C6H4ClNO | 详情 | 详情 |