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【结 构 式】 
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【分子编号】53412 【品名】2,2,2-trichloro-N-[(1S)-2-chloro-2-cyclohexen-1-yl]acetamide 【CA登记号】n/a |
【 分 子 式 】C8H9Cl4NO 【 分 子 量 】276.9764 【元素组成】C 34.69% H 3.28% Cl 51.2% N 5.06% O 5.78% |
合成路线1
该中间体在本合成路线中的序号：(XXV)Treatment of 2-cyclohexenone (XXI) with SO2Cl2 and 2,6-lutidine in dichloromethane provides 2-chloro-2-cyclohexenone (XXII), which is reduced with (S)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c][1,3,2]-oxazaborole and borane dimethyl sulfide complex in THF/MeOH giving (R)-2-chloro-2-cyclohexen-1-ol (XXIII). Reaction of (XXIII) with trichloroacetonitrile by means of NaH in diethyl ether gives the cyclohexenol derivative (XXIV), which is converted into acetamide (XXV) by heating at 140 C in chlorobenzene. Hydrolysis of (XXV) with K2CO3 in water/methanol affords (S)-2-chloro-2-cyclohexen-1-amine (XXVI), which is then condensed with N-phthaloyl-L-phenylalanine acid chloride (VI) in ethyl acetate to yield amide (XXVII). Finally, ozonolysis of amide (XXVII) in CH2Cl2/MeOH, followed by reduction with tributylphosphine and treatment with TFA in refluxing CH2Cl2 provides the previously described intermediate (XII).
| 【1】 del Fresno, M.; Bayes, M.; Castaner, R.M.; Sorbera, L.A.; MDL-100240. Drugs Fut 2002, 27, 5, 458. |
| 【2】 Flynn, G.A. (Merrell Pharmaceuticals, Inc.); Novel process for preparing (S)-1-[2(S)-(1,3-dihydro-1,3-dioxo-isoindo-2-yl)-1-oxo-3-phenylpropyl]-1,2,3,4-tetrahydro-2-pyridine-carboxylic acid methyl ester and intermediates thereof. WO 9514663 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 28292 | (S)-Methyl oxazaborolidine; (3aS)-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole | 112022-81-8 | C18H20BNO | 详情 | 详情 | |
| (VI) | 52756 | (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-phenylpropanoyl chloride | C17H12ClNO3 | 详情 | 详情 | |
| (XII) | 37296 | methyl (2S)-1-[(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-phenylpropanoyl]-1,2,3,4-tetrahydro-2-pyridinecarboxylate | C24H22N2O5 | 详情 | 详情 | |
| (XXI) | 26253 | 2-cyclohexen-1-one；Cyclohex-2-enone；2-cyclohexenone | 930-68-7 | C6H8O | 详情 | 详情 |
| (XXII) | 53409 | 2-chloro-2-cyclohexen-1-one | n/a | C6H7ClO | 详情 | 详情 |
| (XXIII) | 53410 | (1R)-2-chloro-2-cyclohexen-1-ol | n/a | C6H9ClO | 详情 | 详情 |
| (XXIV) | 53411 | (1R)-2-chloro-2-cyclohexen-1-yl 2,2,2-trichloroethanimidoate | n/a | C8H9Cl4NO | 详情 | 详情 |
| (XXV) | 53412 | 2,2,2-trichloro-N-[(1S)-2-chloro-2-cyclohexen-1-yl]acetamide | n/a | C8H9Cl4NO | 详情 | 详情 |
| (XXVI) | 53413 | (1S)-2-chloro-3-cyclohexen-1-amine; (1S)-2-chloro-3-cyclohexen-1-ylamine | n/a | C6H10ClN | 详情 | 详情 |
| (XXVII) | 53414 | (2S)-N-[(1S)-2-chloro-3-cyclohexen-1-yl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-phenylpropanamide | n/a | C23H21ClN2O3 | 详情 | 详情 |