反应 #90736

反应方程式

(3-chloropyrazin-2-yl)methanamine hydrochloride

triethylamine

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

N-ethyl-N-isopropylpropan-2-amine

trichloromethyl carbonochloridate

→

N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxamide

收率 99.0%

溶剂

dichloromethane

tetrahydrofuran

tetrahydrofuran

反应条件

后处理

1. 1
   其他were removed by filtration
2. 2
   浓缩the filtrate was concentrated in vaccuo (50° C. bath temperature)
3. 3
   workup.STIRRINGthe reaction mixture was stirred for three hours
4. 4
   其他The solids were removed by filtration
5. 5
   浓缩the filtrate was concentrated in vacuo
6. 6
   其他Purification

实验过程

A stirred solution of trichloromethyl carbonochloridate (1.038 g, 5.25 mmol) in tetrahydrofuran (10 mL) was cooled to 0° C. and a solution of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride (1 g, 4.37 mmol, J. Med. Chem., 2005, 141) and N-ethyl-N-isopropylpropan-2-amine (1.131 g, 8.75 mmol) in tetrahydrofuran (10 mL) was added slowly in 25 minutes. After stirring at 0° C. for one hour the solids were removed by filtration and the filtrate was concentrated in vaccuo (50° C. bath temperature). The residue was added to a solution of (3-chloropyrazin-2-yl)methanamine hydrochloride (0.788 g, 4.37 mmol) and triethylamine (1.018 g, 10.06 mmol) in dichloromethane (20 mL) and the reaction mixture was stirred for three hours. The solids were removed by filtration and the filtrate was concentrated in vacuo. Purification using column chromatography (silica gel; gradient dichloromethane/methanol 100:0 to 95:5) to afford N-((3-chloropyrazin-2-yl)methyl)-3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxamide (1.56 g, 4.31 mmol, 99% yield). LC-MS: C12H11ClF3N7O: 361. found 362.04[M+H]+, RT=0.42 min.

来源