(2Z)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine

764667-65-4

767340-03-4

Example 1: Preparation of (Z)-3-amino-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl)-4-(2,4,5-trifluorophenyl)but-2-en-1-one. 4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-1-one (427.0 g, prepared according to US 7,326,708 B2 or J. Am. Chem. Soc. 2009) was mixed with methanol (1000 ml) was mixed and passed through dry ammonia (53.6 g) at 25-30°C. The reaction mixture was then heated to reflux (60-65°C) and the reaction was maintained at this temperature for 3.0-4.0 hours. Upon completion of the reaction, the mixture was cooled to 0-5 °C and the precipitated solid was collected by filtration and washed with cold methanol. The wet filter cake was dried at 60-65 °C to afford 340.0 g of the target product (2Z)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine in a molar yield of 79.8% and an HPLC purity of 98.99%.