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【结 构 式】 
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【分子编号】32504 【品名】6-[(2R)oxiranyl][1,2,3,4]tetraazolo[1,5-a]pyridine 【CA登记号】 |
【 分 子 式 】C7H6N4O 【 分 子 量 】162.151 【元素组成】C 51.85% H 3.73% N 34.55% O 9.87% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The condensation of 2-(4-hydroxyphenyl)acetic acid methyl ester (XIII) with 2-(tert-butoxycarbonylamino)ethanol (XV) by means of diethyl azodicarboxylate (DEAD) in THF gives 2-[4-[2-(tert-butoxy carbonyl- amino)ethoxy]phenyl]acetic acid methyl ester (XVI), which is deprotected with TFA in dichloromethane yielding the 2-aminoethoxy derivative (XVII). The addition of (XVII) to the oxiranyl derivative (XVIII) in refluxing methanol affords the intermediate (XIX), which is reduced with SnCl2 in refluxing methanol to give the 6-aminopyridine derivative (XX). Finally, this compound is hydrolyzed to the target compound with KOH in methanol/water. The oxirane intermediate (XVIII) has been obtained by stereocontrolled reductive cyclization of 6-(2-bromoacetyl)tetrazolo[1,5-a]pyridine (XXI) with commercial (R)-Alpine Borane in THF.
| 【1】 Fisher, M.H.; Wyvratt, M.J. (Merck & Co., Inc.); Novel beta-adrenergic agonists. AU 9047392; EP 0377488; JP 1990231486; US 5030640 . |
| 【2】 Dow, R.L. (Pfizer Inc.); beta-Adrenergic agonists. EP 0824519; JP 1999504649; US 5977124; WO 9635671 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 15822 | Methyl 4-hydroxyphenylacetate; methyl 2-(4-hydroxyphenyl)acetate | 14199-15-6 | C9H10O3 | 详情 | 详情 |
| (XV) | 32500 | tert-butyl 2-hydroxyethylcarbamate | 26690-80-2 | C7H15NO3 | 详情 | 详情 |
| (XVI) | 32501 | methyl 2-(4-[2-[(tert-butoxycarbonyl)amino]ethoxy]phenyl)acetate | C16H23NO5 | 详情 | 详情 | |
| (XVII) | 32502 | methyl 2-[4-(2-aminoethoxy)phenyl]acetate | C11H15NO3 | 详情 | 详情 | |
| (XVIII) | 32504 | 6-[(2R)oxiranyl][1,2,3,4]tetraazolo[1,5-a]pyridine | C7H6N4O | 详情 | 详情 | |
| (XIX) | 32503 | methyl 2-[4-(2-[[(2R)-2-hydroxy-2-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-ylethyl]amino]ethoxy)phenyl]acetate | C18H21N5O4 | 详情 | 详情 | |
| (XX) | 32505 | methyl 2-[4-(2-[[(2R)-2-(6-amino-3-pyridinyl)-2-hydroxyethyl]amino]ethoxy)phenyl]acetate | C18H23N3O4 | 详情 | 详情 | |
| (XXI) | 32506 | 2-bromo-1-[1,2,3,4]tetraazolo[1,5-a]pyridin-6-yl-1-ethanone | C7H5BrN4O | 详情 | 详情 |