HRID45607

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID9773

Ethanamine, 2,2,2-trifluoro-

C2H4F3N

HCID81531

Diisopropylethylamine

C8H19N

结构：COC(=O)[C@@H](CC(C)C)N(C(=O)[C@H](NC(=O)OC(C)(C)C)C1Cc2ccccc2C1)[C@@H](C(=O)O)c1ccc(F)cc1

HCID57439045

未命名化合物

PRODUCTS

生成物

结构：CC(C)C[C@@H]1C(=O)N[C@H](C2Cc3ccccc3C2)C(=O)N1[C@@H](C(=O)NCC(F)(F)F)c1ccc(F)cc1

HCID11375822

未命名化合物

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID6228

N,N-Dimethylformamide

C3H7NO

PROCEDURE

实验过程

A solution of (2R)-{[(2R)-2-[(tert-butoxycarbonyl)amino]-2-(2,3-dihydro-1H-inden-2-yl)ethanoyl][(1R)-1-(methoxycarbonyl)-3-methylbutyl]amino}(4-fluorophenyl)ethanoic acid (73 mg) in N,N-dimethylformamide (2 ml) was sequentially treated with diisopropylethylamine (51 μl), phosphorusI (1-hydroxy-1H-benzotriazolato-O)tri-1-pyrrolidinyl-(T-4)-hexafluorophosphate (80 mg) and then after 2 minutes, 2,2,2-trifluoroethylamine (25 μl). This reaction mixture was stirred for 2 hours before being partitioned between 2M aqueous hydrochloric acid and ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine before being dried over magnesium sulphate and evaporated in vacuo. The residue was dissolved in 4M hydrogen chloride in dioxane and stirred for 7 hours at room temperature. The reagent was removed in vacuo and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The separated organic fraction was washed with brine before being dried over magnesium sulphate and evaporated in vacuo. The crude material was purified by column chromatography (silica) eluting with methanol:dichloromethane (1% to 3%) to furnish ((2R)-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-2-(4-fluorophenyl)-N-(2,2,2-trifluoroethyl)ethanamide (10 mg)

WORKUP

后处理

custombefore being partitioned between 2M aqueous hydrochloric acid and ethyl acetate
washThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
dry with materialbefore being dried over magnesium sulphate
customevaporated in vacuo
dissolutionThe residue was dissolved in 4M hydrogen chloride in dioxane
stirringstirred for 7 hours at room temperature
customThe reagent was removed in vacuo
customthe residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
washThe separated organic fraction was washed with brine
dry with materialbefore being dried over magnesium sulphate
customevaporated in vacuo
customThe crude material was purified by column chromatography (silica)
washeluting with methanol

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-d2c49389091e4e5e99cd75694aff8b82
来源数据集: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
专利: US08541579B2
来源说明: uspto-grants-2013_09

反应 SMILES

C(O[C:6]([NH:8][C@H:9]([CH:33]1[CH2:41][C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34]1)[C:10]([N:12]([C@H:22]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C:23](O)=[O:24])[C@@H:13](C(OC)=O)[CH2:14][CH:15]([CH3:17])[CH3:16])=[O:11])=[O:7])(C)(C)C.C(N(C(C)C)CC)(C)C.[F:51][C:52]([F:56])([F:55])[CH2:53][NH2:54]>CN(C)C=O>[CH2:41]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:34][CH:33]1[C@H:9]1[NH:8][C:6](=[O:7])[C@@H:13]([CH2:14][CH:15]([CH3:17])[CH3:16])[N:12]([C@H:22]([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[C:23]([NH:54][CH2:53][C:52]([F:56])([F:55])[F:51])=[O:24])[C:10]1=[O:11]