反应 #471141

反应方程式

(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

diisopropylethylamine

phosphorus

2,2,2-trifluoroethylamine

→

(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

溶剂

N,N-dimethylformamide

反应条件

后处理

1. 1
   其他before being partitioned between 2M aqueous hydrochloric acid and ethyl acetate
2. 2
   洗涤The organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
3. 3
   干燥before being dried over magnesium sulphate
4. 4
   其他evaporated in vacuo
5. 5
   workup.DISSOLUTIONThe residue was dissolved in 4M hydrogen chloride in dioxane
6. 6
   workup.STIRRINGstirred for 7 hours at room temperature
7. 7
   其他The reagent was removed in vacuo
8. 8
   其他the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
9. 9
   洗涤The separated organic fraction was washed with brine
10. 10
    干燥before being dried over magnesium sulphate
11. 11
    其他evaporated in vacuo
12. 12
    其他The crude material was purified by column chromatography (silica)
13. 13
    洗涤eluting with methanol

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), phosphorus, (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)

来源