反应详情

In a 250 mL round bottom flask THF (225 mL) was taken. It was cooled to less than −5° C. and NaBH4 (5.62 g) was added. After that methanesulfonic acid (17.8 g) was added dropwise at less than −5° C. over a period of 30 min. 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine (20.0 g) is mixed in a solvent mixture of THF (50 mL) and IPA (22 mL) and added into the reaction mixture, keeping the temperature below 0° C. It was stirred for 4-6 h below 5° C. After usual work-up procedure, product was extracted in a suitable solvent. Extract was washed and dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-20.8 g, % Purity by HPLC-80.7% and % of 3-hydroxy-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one by HPLC-15.5%).

1. temperatureIt was cooled to less than −5° C.
2. additionadded into the reaction mixture
3. customthe temperature below 0° C
4. extractionAfter usual work-up procedure, product was extracted in a suitable solvent
5. extractionExtract
6. washwas washed
7. dry with materialdried over anhydrous sodium sulfate
8. customSolvent was evaporated at reduced pressure
9. customto obtain the product