【结 构 式】 |
【分子编号】38550 【品名】methyl (2S)-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butanoate 【CA登记号】 |
【 分 子 式 】C10H18N2O3 【 分 子 量 】214.2646 【元素组成】C 56.06% H 8.47% N 13.07% O 22.4% |
合成路线1
该中间体在本合成路线中的序号:(XXI)The intermediate 3-methyl 2(S)-(2-oxoperhydropyrimidin1-yl)butyric acid (XIII) has been obtained as follows: The oxidation of 3-(benzyloxycarbonylamino)-1-propanol (XVII) with oxalyl chloride in dichloromethane gives the corresponding aldehyde (XVIII), which is reductocondensed with L-valine methyl ester (XIX) by means NaBH3CN in methanol yielding the N-substituted valine (XX). The cyclization of (XX) by elimination of the benzyloxycarbonyl group by hydrogenation with H2 over Pd/C in dichloromethane, followed by reaction with carbonyldiimidazole (CDI) affords the 3-methyl 2(S)-(2-oxoperhydropyrimidin-1-yl)butyric acid methyl ester (XXI). Finally, this compound is hydrolyzed with LiOH in dioxane/water to afford the target intermediate (XIII).
【1】 Retroviral protease inhibiting cpds.. EP 0882024; JP 2000502085; US 5914332; WO 9721685 . |
【2】 Sham, H.L.; Stewart, K.D.; Kempf, D.J. (Abbott Laboratories Inc.); Retroviral protease inhibiting cpds.. EP 0876353; JP 2000502997; WO 9721683 . |
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) | 38264 | (2S)-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butyric acid | C9H16N2O3 | 详情 | 详情 | |
(XVII) | 38547 | benzyl 3-hydroxypropylcarbamate | C11H15NO3 | 详情 | 详情 | |
(XVIII) | 38548 | benzyl 3-oxopropylcarbamate | C11H13NO3 | 详情 | 详情 | |
(XIX) | 16613 | methyl (2S)-2-amino-3-methylbutanoate | C6H13NO2 | 详情 | 详情 | |
(XX) | 38549 | methyl (2S)-2-[(3-[[(benzyloxy)carbonyl]amino]propyl)amino]-3-methylbutanoate | C17H26N2O4 | 详情 | 详情 | |
(XXI) | 38550 | methyl (2S)-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butanoate | C10H18N2O3 | 详情 | 详情 |