反应 #90754

反应方程式

3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid

(COCl)2

(3-chloropyrazin-2-yl)methanamine hydrochloride

DIEA

→

3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide

收率 49.3%

溶剂

THF

DMF

反应条件

后处理

1. 1
   其他the solvent was removed
2. 2
   workup.DISSOLUTIONThe resulting residue was dissolved in THF (35 mL)
3. 3
   workup.STIRRINGthe mixture was stirred at 60° C. for 1 h
4. 4
   其他Remove the solvent in vacuo
5. 5
   萃取the residue was extracted with DCM
6. 6
   洗涤the combined organic layer was washed with water, brine
7. 7
   干燥dried over anhydrous Na2SO4
8. 8
   浓缩The organic layer was concentrated in vacuo
9. 9
   其他the residue was purified by silica gel column chromatography (DCM/THF=100/20)

实验过程

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%).

来源