Reaktion #73885

Reaktionsgleichung

2,2,2-trifluoroethylamine

(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

→

(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

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigebefore being partitioned between 2M aqueous hydrochloric acid and ethyl acetate
2. 2
   WaschenThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
3. 3
   Trocknenbefore being dried over magnesium sulphate
4. 4
   Sonstigeevaporated 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
   SonstigeThe reagent was removed in vacuo
8. 8
   Sonstigethe residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
9. 9
   WaschenThe separated organic fraction was washed with brine
10. 10
    Trocknenbefore being dried over magnesium sulphate
11. 11
    Sonstigeevaporated in vacuo
12. 12
    SonstigeThe crude material was purified by column chromatography (silica)
13. 13
    Wascheneluting with methanol

Vorschrift

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)

Quelle