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【结 构 式】 
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【分子编号】62956 【品名】ethyl [3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methylcarbamate 【CA登记号】 |
【 分 子 式 】C14H19NO4 【 分 子 量 】265.3092 【元素组成】C 63.38% H 7.22% N 5.28% O 24.12% |
合成路线1
该中间体在本合成路线中的序号：(IV)Reduction of 4,5-dimethoxybenzocyclobutane-1-carbonitrile (I) with BH3 in THF gives 4,5-dimethoxybenzocyclobutan-1-ylmethylamine (II), which is treated with ethyl chloroformate (III) and triethylamine in dichloromethane to yield carbamate (IV). Reduction of carbamate (IV) by means of LiAlH4 in THF provides racemic N-(4,5-dimethoxybenzocyclobutan-1-yl)-N-methylamine (V), which is submitted to optical resolution with camphorsulfonic acid (CSA) to afford the desired (S)-enantiomer (VI). Reaction of the known 3-(3-chloropropyl)-7,8-dimethoxy-2,3-dihydro-1H-3-benzazepin-2-one (VII) with NaI in acetone yields the corresponding 3-iodopropyl derivative (VIII), which is condensed with the chiral amine (VI) by means of K2CO3 in acetone to afford adduct (IX). Finally, this compound is hydrogenated with H2 over Pd(OH)2 in AcOH.
| 【2】 Peglion, J.-L.; Vian, J.; Vilaine, J.-P.; Villeneuve, N.; Janiak, P.; Bidouard, J.-P. (ADIR et Cie.); Benzocyclobutyl- or indanyl-alkyl-amino-alkyl substd. 3-benzazepin-2-ones useful in the treatment of cardiovascular diseases. EP 0534859; FR 2681862; JP 1993213890; US 5296482 . |
| 【1】 Sorbera, L.A.; Castaner, J.; Ivabradine Hydrochloride. Drugs Fut 2003, 28, 7, 652. |
| 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) | 62954 | 3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile | C11H11NO2 | 详情 | 详情 | |
| (II) | 62955 | [3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine; [3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methylamine | C11H15NO2 | 详情 | 详情 | |
| (III) | 11229 | 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate | 541-41-3 | C3H5ClO2 | 详情 | 详情 |
| (IV) | 62956 | ethyl [3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methylcarbamate | C14H19NO4 | 详情 | 详情 | |
| (V) | 62957 | N-{[3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-N-methylamine; [3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine | C12H17NO2 | 详情 | 详情 | |
| (VI) | 62958 | N-{[3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-N-methylamine; [3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]-N-methylmethanamine | C12H17NO2 | 详情 | 详情 | |
| (VII) | 24899 | 3-(3-chloropropyl)-7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one | C15H18ClNO3 | 详情 | 详情 | |
| (VIII) | 62959 | 3-(3-iodopropyl)-7,8-bis(methyloxy)-1,3-dihydro-2H-3-benzazepin-2-one | C15H18INO3 | 详情 | 详情 | |
| (IX) | 62960 | 3-{3-[{[3,4-bis(methyloxy)bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino]propyl}-7,8-bis(methyloxy)-1,3-dihydro-2H-3-benzazepin-2-one | C27H34N2O5 | 详情 | 详情 |