反応 #90736

反応方程式

(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

収率 99.0%

溶媒

dichloromethane

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

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

実験手順

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.

出典