반응 #220245

반응 방정식

2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine

2-(Trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine

(3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid

Intermediate 3

(3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid

hydroxybenzotriazole

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

title compound

7-[(3R)-3-[(tert-Butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoyl]-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine

용매

DMF

반응 조건

후처리

1. 1
   기타After removal of the ice-bath
2. 2
   workup.STIRRINGto stir at ambient temperature for 16 h
3. 3
   기타After removal of the DMF
4. 4
   기타by evaporation
5. 5
   기타the residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
6. 6
   추출The aqueous layer was extracted three times with ethyl acetate
7. 7
   세척The combined organic layers were washed with brine
8. 8
   건조dried over magnesium sulfate
9. 9
   농축Concentration

실험 절차

To a solution of 2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine (28.8 mg, 0.15 mmol, from Step D) and (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (Intermediate 3, 50.0 mg, 0.15 mmol) in DMF (3 mL) was added hydroxybenzotriazole (HOBT, 26.1 mg, 0.19 mmol) at 0° C. The reaction was stirred at 0° C. for 5 min, then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 37.0 mg, 0.19 mmol) was added. After removal of the ice-bath, the reaction was allowed to stir at ambient temperature for 16 h. After removal of the DMF by evaporation, the residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over magnesium sulfate. Concentration followed by preparative TLC (10% methanol/dichloromethane) gave the title compound as a foamy solid.

출처