تفاعل #471141

معادلة التفاعل

(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

المذيبات

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   أخرىbefore being partitioned between 2M aqueous hydrochloric acid and ethyl acetate
2. 2
   غسيلThe organic layer was washed with saturated aqueous sodium bicarbonate solution and brine
3. 3
   تجفيفbefore being dried over magnesium sulphate
4. 4
   أخرىevaporated 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
   أخرىThe reagent was removed in vacuo
8. 8
   أخرىthe residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
9. 9
   غسيلThe separated organic fraction was washed with brine
10. 10
    تجفيفbefore being dried over magnesium sulphate
11. 11
    أخرىevaporated in vacuo
12. 12
    أخرىThe crude material was purified by column chromatography (silica)
13. 13
    غسيلeluting with methanol

الإجراء التجريبي

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)

المصدر