反応 #90754

反応方程式

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

収率 49.3%

溶媒

THF

DMF

反応条件

後処理

1. 1
   その他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
   その他Remove the solvent in vacuo
5. 5
   抽出the residue was extracted with DCM
6. 6
   洗浄the combined organic layer was washed with water, brine
7. 7
   乾燥dried over anhydrous Na2SO4
8. 8
   濃縮The organic layer was concentrated in vacuo
9. 9
   その他the residue was purified by silica gel column chromatography (DCM/THF=100/20)

実験手順

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%).

出典