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【结 构 式】 
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【分子编号】37631 【品名】(1R,2S,4R,5S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]nonan-7-ol；Scopine 【CA登记号】498-45-3 |
【 分 子 式 】C8H13NO2 【 分 子 量 】155.19676 【元素组成】C 61.91% H 8.44% N 9.03% O 20.62% |
与该中间体有关的原料药合成路线共 2 条
合成路线1
该中间体在本合成路线中的序号：(IV)The Grignard condensation of oxalic acid dimethyl ester (I) with 2-thienylmagnesium bromide (II) gives 2-hydroxy-2,2-bis(2-thienyl)acetic acid methyl ester (III), which is submitted to transesterification with scopine (IV) catalyzed by Na or NaOEt, providing the corresponding ester (V). Finally, (V) is quaternized with methyl bromide in dichloromethane/acetonitrile.
| 【1】 Banholzer, R.; Bauer, R.; Reichl, R. (Boehringer Ingelheim GmbH; Boehringer Ingelheim Pharma KG); Thienylcarboxylic acid ester of aminoalcohols, their quaternary products, their preparation and use of the cpds.. DE 3931041; EP 0418716; JP 1993502438; US 5610163; WO 9104252 . |
| 【2】 Norman, P.; Rabasseda, X.; Castaner, J.; Graul, A.; Tiotropium Bromide. Drugs Fut 2000, 25, 7, 693. |
| 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) | 37412 | methyl 2-methoxy-2-oxoacetate;dimethyl oxalate;Methyl oxalate | 553-90-2 | C4H6O4 | 详情 | 详情 |
| (II) | 32082 | bromo(2-thienyl)magnesium | 5713-61-1 | C4H3BrMgS | 详情 | 详情 |
| (III) | 37630 | methyl 2-hydroxy-2,2-di(2-thienyl)acetate | 26447-85-8 | C11H10O3S2 | 详情 | 详情 |
| (IV) | 37631 | (1R,2S,4R,5S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]nonan-7-ol；Scopine | 498-45-3 | C8H13NO2 | 详情 | 详情 |
| (V) | 37632 | (1R,2S,4R,5S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]non-7-yl 2-hydroxy-2,2-di(2-thienyl)acetate；Scopine 2,2-dithienylglycolate | 136310-64-0 | C18H19NO4S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号： (VI)
| 【1】 冉臆峰，吕良忠，许军等．2006．毫托澳饺无水钧制备方法．发明专利申请公开说明书，CN 1861598 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 37631 | (1R,2S,4R,5S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]nonan-7-ol；Scopine | 498-45-3 | C8H13NO2 | 详情 | 详情 |
| (I) | 13681 | 2-Bromothiophene | 1003-09-4 | C4H3BrS | 详情 | 详情 |
| (II) | 32082 | bromo(2-thienyl)magnesium | 5713-61-1 | C4H3BrMgS | 详情 | 详情 |
| (III) | 37630 | methyl 2-hydroxy-2,2-di(2-thienyl)acetate | 26447-85-8 | C11H10O3S2 | 详情 | 详情 |
| (IV) | 66859 | C17H21NO4.HBr.3H2O | 详情 | 详情 | ||
| (V) | 37632 | (1R,2S,4R,5S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.0(2,4)]non-7-yl 2-hydroxy-2,2-di(2-thienyl)acetate；Scopine 2,2-dithienylglycolate | 136310-64-0 | C18H19NO4S2 | 详情 | 详情 |
Extended Information