Oxalyl chloride → 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide

To a solution of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid (1.63 g, 6.93 mmol) in THF (35 mL) was added dropwise (COCl)2 (4.4 g, 34.66 mmol) and 0.1 mL of DMF at 0° C., the mixture was stirred at this temperature for 1 hours and then the solvent was removed. The resulting residue was dissolved in THF (35 mL), (3-chloropyrazin-2-yl)methanamine hydrochloride (1.37 g, 7.63 mmol) and DIEA (2.68 g, 20.79 mmol) was added, the mixture was stirred at 60° C. for 1 h. Remove the solvent in vacuo and the residue was extracted with DCM and the combined organic layer was washed with water, brine and dried over anhydrous Na2SO4. The organic layer was concentrated in vacuo and the residue was purified by silica gel column chromatography (DCM/THF=100/20) to afford N4(3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (0.8 g, yield 32%).

1. customthe solvent was removed
2. dissolutionThe resulting residue was dissolved in THF (35 mL)
3. stirringthe mixture was stirred at 60° C. for 1 h
4. customRemove the solvent in vacuo
5. extractionthe residue was extracted with DCM
6. washthe combined organic layer was washed with water, brine
7. dry with materialdried over anhydrous Na2SO4
8. concentrationThe organic layer was concentrated in vacuo
9. customthe residue was purified by silica gel column chromatography (DCM/THF=100/20)

ORD record

ord-46a5574f15624fc8bc99b20e7bb7552f

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09446130B2