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【结 构 式】 
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【分子编号】27157 【品名】(2R)-3-cyclohexyl-2-methylpropanoyl chloride 【CA登记号】 |
【 分 子 式 】C10H17ClO 【 分 子 量 】188.69708 【元素组成】C 63.65% H 9.08% Cl 18.79% O 8.48% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The reaction of (XIII) with HCl in dioxane eliminates the carbamate protecting group giving (XIV) with a free amino group, which is condensed with N-(tert-butoxycarbonyl)-N-methyl-L-valine (XV) by means of NMM and TBTU in dichloromethane to provide the intermediate (XVI) with four amide groups. Elimination of the ter-butyl carbamate group of (XVI) with HCl in dioxane affords compound (XVII) with a reactive methylamino group, which is finally condensed with 3-cyclohexyl-2(R)-methylpropionyl chloride (XVIII) by means of NMM in dichloromethane to afford the target compound.
| 【1】 Gauthier, J.-A.; Moss, N. (Bio-Mega, Inc.; Boehringer Ingelheim GmbH); Herpes ribonucleotide reductase inhibitors. EP 0837845; JP 1999508246; US 5672586; WO 9700855 . |
| 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) | 27152 | benzyl 1-((1S)-1-[[(2R,5S)-5-[(tert-butoxycarbonyl)amino]-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-4-oxoheptanoyl]amino]-2-[[(1R)-1-ethyl-2,2-dimethylpropyl]amino]-2-oxoethyl)cyclopentanecarboxylate | C42H67N3O8 | 详情 | 详情 | |
| (XIV) | 27153 | benzyl 1-((1S)-1-[[(2R,5S)-5-amino-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-4-oxoheptanoyl]amino]-2-[[(1R)-1-ethyl-2,2-dimethylpropyl]amino]-2-oxoethyl)cyclopentanecarboxylate | C37H59N3O6 | 详情 | 详情 | |
| (XV) | 27154 | (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-methylbutyric acid | 45170-31-8 | C11H21NO4 | 详情 | 详情 |
| (XVI) | 27155 | benzyl 1-[(1S,4R,7S,10S)-7-(tert-butyl)-4-(3,3-dimethyl-2-oxobutyl)-1-([[(1R)-1-ethyl-2,2-dimethylpropyl]amino]carbonyl)-10-isopropyl-11,14,14-trimethyl-3,6,9,12-tetraoxo-13-oxa-2,8,11-triazapentadec-1-yl]cyclopentanecarboxylate | C48H78N4O9 | 详情 | 详情 | |
| (XVII) | 27156 | 1-((1S)-1-[((2R,5S)-2-(3,3-dimethyl-2-oxobutyl)-6,6-dimethyl-5-[[(2S)-3-methyl-2-(methylamino)butanoyl]amino]-4-oxoheptanoyl)amino]-2-[[(1R)-1-ethyl-2,2-dimethylpropyl]amino]-2-oxoethyl)cyclopentanecarboxylic acid | C36H64N4O7 | 详情 | 详情 | |
| (XVIII) | 27157 | (2R)-3-cyclohexyl-2-methylpropanoyl chloride | C10H17ClO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVIII)The intermediate 3-cyclohexyl-2(R)-methylpropionyl chloride (XVIII) has been obtained as follows: The reaction of 4(S)-isopropyloxazolidin-2-one (XIX) with propionyl chloride (XX) by means of BuLi in THF gives 4(S)-isopropyl-3-propionyloxazolidin-2-one (XXI), which is condensed with benzyl bromide (XXII) by means of LHMDS in THF yielding 4(S)-isopropyl-3-(2(R)-methyl-3-phenylpropionyl)oxazolidin-2-one (XXIII). The oxidative cleavage of (XXIII) with H2O2 in THF/water affords 2(R)-methyl-3-phenylpropionic acid (XXIV), which is hydrogenated with H2 over alumina providing 3-cyclohexyl-2(R)-methylpropionic acid (XXV). Finally, this compound is treated with oxalyl chloride in DMF to afford the desired intermediate 3-cyclohexyl-2(R)-methylpropionyl chloride (XVIII).
| 【1】 Gauthier, J.-A.; Moss, N. (Bio-Mega, Inc.; Boehringer Ingelheim GmbH); Herpes ribonucleotide reductase inhibitors. EP 0837845; JP 1999508246; US 5672586; WO 9700855 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 27157 | (2R)-3-cyclohexyl-2-methylpropanoyl chloride | C10H17ClO | 详情 | 详情 | |
| (XIX) | 12867 | (4S)-4-Isopropyl-1,3-oxazolidin-2-one; (R)-4-Isopropyl-2-oxazolidinone | 17016-83-0 | C6H11NO2 | 详情 | 详情 |
| (XX) | 15967 | propanoyl chloride; propionyl chloride | 79-03-8 | C3H5ClO | 详情 | 详情 |
| (XXI) | 11535 | (4S)-4-Isopropyl-3-propionyl-1,3-oxazolidin-2-one | 77877-19-1 | C9H15NO3 | 详情 | 详情 |
| (XXII) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (XXIII) | 27167 | (4S)-4-isopropyl-3-[(2R)-2-methyl-3-phenylpropanoyl]-1,3-oxazolidin-2-one | C16H21NO3 | 详情 | 详情 | |
| (XXIV) | 27168 | (2R)-2-methyl-3-phenylpropionic acid | C10H12O2 | 详情 | 详情 | |
| (XXV) | 27169 | (2R)-3-cyclohexyl-2-methylpropionic acid | C10H18O2 | 详情 | 详情 |