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【结 构 式】 
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【分子编号】65990 【品名】 【CA登记号】 |
【 分 子 式 】C15H20N2O4 【 分 子 量 】292.33488 【元素组成】C 61.63% H 6.9% N 9.58% O 21.89% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The precursors N-(benzyloxycarbonyl)-N-[1-(benzyloxycarbonyl)-3(R)-pyrrolidinyl]glycine (XII) and its dicyclohexylamine salt (XIII) are prepared as follows. Alkylation of 3(R)-amino-1-(benzyloxycarbonyl)pyrrolidine or its hydrochloride (XVI) with methyl 2-bromoacetate (XVII) by means of K2CO3 in MTBE/H2O yields the amino ester (XVIII), which, without isolation, is further protected with benzyloxycarbonyl chloride to provide the diprotected compound (XIX). Hydrolysis of the methyl ester (XIX) with NaOH in refluxing MTBE/H2O followed by in situ treatment of the obtained sodium salt with HCl leads to the carboxylic acid (XII) , which by treatment with dicyclohexylamine in THF provides the corresponding dicyclohexylammonium salt (XIII) .
| 【1】 Wu, Z.P., Campbell, D.A., Cherrington, J.M. (Phenomix Corp.). Solid citrate and tartrate salts of DPP-IV inhibitors. EP 2061474, JP 2010502610, WO 2008027273. |
| 【4】 Campbell, D.A., Winn, D.T. (Phenomix Corp.). Methods of preparing heterocyclic boronic acids and derivatives thereof. EP 1919485, JP 2009503077, US 2008300413, WO2007016356. |
| 【6】 Campbell, D.A., Leitao, E.P.T., Wu, Z.-P., Wang, P. (Phenomix Corp.). Methods and intermediates for synthesis of selective DPP-IV inhibitors. EP 2173709, WO 2008109681. |
| 【7】 Wang, P. (Phenomix Corp.). A crystalline synthetic intermediate for pyrrolidin-3-yl-glycylaminoalkylboronates. WO 2009094462. |
| 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) | 63162 | 2-[(E)-2-phenyldiazenyl]malononitrile | 6017-21-6 | C9H6N4 | 详情 | 详情 |
| (XIII) | 63163 | 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-2-phenyldiazenyl]-4,6-pyrimidinediamine; 6-amino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-[(E)-2-phenyldiazenyl]-4-pyrimidinylamine | 428854-23-3 | C23H18FN9 | 详情 | 详情 |
| (XVI) | 65989 | (3R)-1-Cbz-3-Aminopyrrolidine hydrochloride | 870621-17-3 | C12H16N2O2.HCl | 详情 | 详情 |
| (XVII) | 12309 | methyl 2-bromoacetate; methyl bromoacetate | 96-32-2 | C3H5BrO2 | 详情 | 详情 |
| (XVIII) | 65990 | C15H20N2O4 | 详情 | 详情 | ||
| (XIX) | 65991 | C23H26N2O6 | 详情 | 详情 |