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【结 构 式】 
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【药物名称】NIP-141 【化学名称】N-[(3R*,4S*)-4-(Cyclopropylamino)-3-hydroxy-2,2-dimethyl-7-nitro-3,4-dihydro-2H-1-benzopyran-6-yl]-2-(4-methoxyphenyl)acetamide hydrochloride 【CA登记号】203002-58-8 (free base) 【 分 子 式 】C23H28ClN3O6 【 分 子 量 】477.94911 |
【开发单位】Nissan Chemical (Originator) 【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, Potassium Channel Blockers |
合成路线1
The acylation of 6-amino-2,2-dimethyl-7-nitro-2H-1-benzopyran (I) with p-methoxyphenylacetyl chloride (II) furnished amide (III). Subsequent bromination of the pyran ring of (III) employing N-bromosuccinimide in H2O-DMSO formed the trans bromohydrin (IV), which was further cyclized to epoxide (V) upon treatment with NaOH. Finally, oxirane ring opening in (IV) with cyclopropylamine (VI) in boiling EtOH yielded the title trans amino alcohol.
| 【1】 Tanikawa, K.; Ohrai, K.; Sato, M.; Yamashita, T.; Yanagihara, K. (Nissan Chemical Industry, Ltd.); Chroman derivs.. EP 0934296; JP 1998087650; US 6066631; WO 9804542 . |
| 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) | 26757 | 2,2-dimethyl-7-nitro-2H-chromen-6-amine | C11H12N2O3 | 详情 | 详情 | |
| (II) | 26758 | 2-(4-methoxyphenyl)acetyl chloride | 4693-91-8 | C9H9ClO2 | 详情 | 详情 |
| (III) | 26759 | N-(2,2-dimethyl-7-nitro-2H-chromen-6-yl)-2-(4-methoxyphenyl)acetamide | C20H20N2O5 | 详情 | 详情 | |
| (IV) | 59601 | N-[(3S,4R)-3-bromo-4-hydroxy-2,2-dimethyl-7-nitro-3,4-dihydro-2H-chromen-6-yl]-2-(4-methoxyphenyl)acetamide | C20H21BrN2O6 | 详情 | 详情 | |
| (V) | 26760 | N-[(1aR,7bR)-2,2-dimethyl-5-nitro-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl]-2-(4-methoxyphenyl)acetamide | C20H20N2O6 | 详情 | 详情 | |
| (VI) | 12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 |