|
【结 构 式】 
|
【分子编号】44272 【品名】tert-butyl (1R)-2-([[(Z,2R)-1-[[(3,5-dichlorobenzoyl)(methyl)amino]methyl]-2-(3,4-dichlorophenyl)-5-methyl-4-hexenylidene]amino]oxy)-2-oxo-1-phenylethylcarbamate 【CA登记号】 |
【 分 子 式 】C35H37Cl4N3O5 【 分 子 量 】721.5068 【元素组成】C 58.26% H 5.17% Cl 19.65% N 5.82% O 11.09% |
合成路线1
该中间体在本合成路线中的序号：(X)Acylation of sarcosine methyl ester (I) with 3,5-dichlorobenzoyl chloride (II) produced the corresponding amide (III). Claisen condensation of (III) with the dianion of 3,4-dichlorophenylacetic acid (IV), generated in the presence of lithium hexamethyldisilazide, gave, after acid decarboxylation, ketone (V). The lithium enolate of ketone (V) was then alkylated with 1-bromo-3-methyl-2-butene (VI) to afford (VII). Treatment of ketone (VII) with hydroxylamine produced a geometric mixture of oximes from which the desired (E)-isomer (VIII) was isolated by column chromatography. Resolution of the racemic (VIII) was achieved by coupling with N-Boc-D-phenylglycine (IX) followed by fractional crystallization of the desired diastereoisomer (X). Hydrazinolysis of the oxime ester then furnished the chiral intermediate (XI).
| 【1】 Carruthers, N.I.; Alaimo, C.A.; Shih, N.-Y.; Lavey, B.J.; Ting, P.C.; Reichard, G.A. (Schering Corp.); Substd. oximes as neurokinin antagonists. EP 1032561; WO 9926924 . |
| 【2】 Carruthers, N.I.; Reichard, G.A.; Shih, N.-Y.; Lavey, B.J.; Alaimo, C.A.; Ting, P.C. (Schering Corp.); Substd. oximes as neurokinin antagonists. US 6063926 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 10430 | methyl 2-(methylamino)acetate; methyl N-methylglycinate | 5473-12-1 | C4H9NO2 | 详情 | 详情 |
| (II) | 27769 | 3,5-dichlorobenzoyl chloride | 2905-62-6 | C7H3Cl3O | 详情 | 详情 |
| (III) | 44268 | methyl 2-[(3,5-dichlorobenzoyl)(methyl)amino]acetate | C11H11Cl2NO3 | 详情 | 详情 | |
| (IV) | 30414 | 2-(3,4-dichlorophenyl)acetic acid；2-(3,4-Dichlorophenyl)acetic acid | 5807-30-7 | C8H6Cl2O2 | 详情 | 详情 |
| (V) | 44269 | 3,5-dichloro-N-[3-(3,4-dichlorophenyl)-2-oxopropyl]-N-methylbenzamide | C17H13Cl4NO2 | 详情 | 详情 | |
| (VI) | 12989 | 4-Bromo-2-methyl-2-butene; 1-Bromo-3-methyl-2-butene | 870-63-3 | C5H9Br | 详情 | 详情 |
| (VII) | 44270 | 3,5-dichloro-N-[3-(3,4-dichlorophenyl)-6-methyl-2-oxo-5-heptenyl]-N-methylbenzamide | C22H21Cl4NO2 | 详情 | 详情 | |
| (VIII) | 44271 | 3,5-dichloro-N-[3-(3,4-dichlorophenyl)-2-(hydroxyimino)-6-methyl-5-heptenyl]-N-methylbenzamide | C22H22Cl4N2O2 | 详情 | 详情 | |
| (IX) | 22613 | (2R)-2-[(tert-butoxycarbonyl)amino]-2-phenylethanoic acid | 2900-27-8 | C13H17NO4 | 详情 | 详情 |
| (X) | 44272 | tert-butyl (1R)-2-([[(Z,2R)-1-[[(3,5-dichlorobenzoyl)(methyl)amino]methyl]-2-(3,4-dichlorophenyl)-5-methyl-4-hexenylidene]amino]oxy)-2-oxo-1-phenylethylcarbamate | C35H37Cl4N3O5 | 详情 | 详情 | |
| (XI) | 44273 | 3,5-dichloro-N-[(3R)-3-(3,4-dichlorophenyl)-2-(hydroxyimino)-6-methyl-5-heptenyl]-N-methylbenzamide | C22H22Cl4N2O2 | 详情 | 详情 |