ChemicalBook CAS DataBase List (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)butan-2-one

(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)butan-2-one synthesis

8synthesis methods

Product Name:(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)butan-2-one
CAS Number:764667-65-4
Molecular formula:C16H12F6N4O2
Molecular Weight:406.28

ethyl 3-oxo-4-(2,4,5-trifluorophenyl)butanoate

1151240-88-8

3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine

486460-21-3

(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)butan-2-one

764667-65-4

Potassium tert-butoxide (2.24 g, 20 mmol) was dissolved in 40 mL of tetrahydrofuran in a 100 mL single-necked flask and stirred for 1 min at room temperature. Subsequently, ethyl 3-oxo-4-(2,4,5-trifluorophenyl)butanoate (1.91 g, 10 mmol) and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (2.60 g, 10 mmol) were added sequentially and stirring was continued for 60 min at room temperature. After completion of the reaction, the tetrahydrofuran was removed by distillation under reduced pressure. The residue was extracted by adding 50 mL of water and 50 mL of dichloromethane to the residue. The organic phase was separated and dried over anhydrous sodium sulfate, followed by evaporation of the solvent. The crude product was recrystallized by dichloromethane and cyclohexane to give 3.33 g of 1-(3-trifluoromethyl-5,6-dihydro-8H-[1,2,4]triazol-[4,3-A]pyrazine-7(8H)-yl)-4-(2,4,5-trifluorophenyl)-1,3-butanedione in 82% yield and 99% purity.

209995-38-0 Synthesis

209995-38-0
520 suppliers
$10.00/10 g

762240-92-6 Synthesis

3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride

762240-92-6
551 suppliers
$25.00/1 g

764667-65-4
248 suppliers
$6.00/1g

Yield:764667-65-4 89%

Reaction Conditions:

Stage #1:(2,4,5-trifluorophenyl)acetic acid with cycl-isopropylidene malonate;N-ethyl-N,N-diisopropylamine;dmap in ISOPROPYLAMIDE at 20 - 40;
Stage #2: with pivaloyl chloride in ISOPROPYLAMIDE at 0 - 5; for 1 - 3 h;
Stage #3:3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride in ISOPROPYLAMIDE at 40 - 70;

Steps:

2; A Scheme 2; Step A : Preparation of 4-oxo-4-[3-(trifluoromethyl)-5,6- dihydro[1,2,4]triazolo[4,3-a]pyrazin- 7 (8H)-YLL-1- (2, 4, 5- TRIFLUOROPHENVL) butan-2-one (2-3)
2,4, 5-TRIFLUOROPHENYLACETIC acid (2-1) (150 g, 0.789 MOL), Meldrum's acid (125 g, 0.868 mol), and 4- (DIMETHYLAMINO) pyridine (DMAP) (7.7 g, 0063 mol) were charged into a 5 L three-neck flask. N, N-DIMETHYLACETAMIDE (DMAC) (525 mL) was added in one portion at room temperature to dissolve the solids. N, N-DIISOPROPYLETHYLAMINE (282 mL, 1.62 mol) was added in one portion at room temperature while maintaining the temperature below 40 °C. Pivaloyl chloride (107 ML, 0.868 mol) was added dropwise over 1 to 2 h while maintaining the temperature between 0 and 5 °C. The reaction mixture was aged at 5 °C for 1 h. Triazole hydrochloride 1-4 (180 g, 0.789 mol) was added in one portion at 40-50 °C. The reaction solution was aged at 70 °C for several h. 5% Aqueous sodium hydrogencarbonate solution (625 ML) was then added dropwise at 20-45 °C. The batch was seeded and aged at 20-30 °C for 1-2 h. Then an additional 525 mL of 5% aqueous sodium hydrogencarbonate solution was added dropwise over 2-3 h. After aging several h at room temperature, the slurry was cooled to 0-5 °C and aged 1 h before filtering the solid. The wet cake was displacement-washed with 20% aqueous DMAC (300 mL), followed by an additional two batches of 20% aqueous DMAC (400 mL), and finally water (400 mL). The cake was suction-dried at room temperature. The isolated yield of final product 2-3 was 89%.

References:

MERCK & CO., INC. WO2005/3135, 2005, A1 Location in patent:Page 12-13

FullText

2033-24-1 Synthesis