反应 #1135884

反应方程式

cyanoborohydride

(3-((3-(trifluoromethyl)phenyl)ethynyl) imidazo[1,2-a]pyridin-2-yl) methanamine

2-oxoacetic acid hydrate

→

2-(((3-((3-(trifluoromethyl)phenyl)ethynyl) imidazo[1,2-a]pyridin-2-yl)methyl)amino) acetic acid

收率 22.0%

溶剂

dichloromethane

methanol

反应条件

后处理

1. 1
   其他In a reactor equipped with
2. 2
   过滤a filter
3. 3
   其他dichloromethane was removed by filtration
4. 4
   workup.ADDITIONwas added
5. 5
   workup.STIRRINGThe mixture was stirred under a slow vortex at r.t. for 24 h
6. 6
   其他The resin was removed by filtration
7. 7
   洗涤washed with 15 ml of methanol, 15 ml of dichloromethane
8. 8
   浓缩The obtained filtrate was concentrated in vacuo
9. 9
   其他the residue was purified by flash chromatography on a silica gel cartridge (eluent: dichloromethane/methanol/aqueous ammonia (20% by mass), 80/20/2, v/v/v)

实验过程

In a reactor equipped with a filter and an emptying system and placed on a vortex, were introduced 0.33 g (0.656 mmol) of cyanoborohydride resin. The resin was swelled in 3 ml of dichloromethane, the mixture was stirred at r.t. for 10 min and then dichloromethane was removed by filtration. The operation was repeated a second time and then a mixture of 0.2 g of (3-((3-(trifluoromethyl)phenyl)ethynyl) imidazo[1,2-a]pyridin-2-yl) methanamine and 0.055 g (0.596 mmol) of 2-oxoacetic acid hydrate solubilised in 3 ml of methanol was added. The mixture was stirred under a slow vortex at r.t. for 24 h. The resin was removed by filtration, washed with 15 ml of methanol, 15 ml of dichloromethane and then again 15 ml of methanol. The obtained filtrate was concentrated in vacuo and the residue was purified by flash chromatography on a silica gel cartridge (eluent: dichloromethane/methanol/aqueous ammonia (20% by mass), 80/20/2, v/v/v). 0.049 g (yield=22%) of 2-(((3-((3-(trifluoromethyl)phenyl)ethynyl) imidazo[1,2-a]pyridin-2-yl)methyl)amino) acetic acid were obtained as a white solid. LC-MS: m/z=374 (MH+); UV purity at 254 nm=98%. 1H NMR (300 MHz, DMSO) δ 8.76 (d, J=6.7 Hz, 1H), 8.13 (s, 1H), 8.01 (d, J=7.6 Hz, 1H), 7.78 (d, J=7.9 Hz, 1H), 7.69 (dd, J=8.3, 7.1 Hz, 2H), 7.53-7.42 (m, 1H), 7.16 (td, J=6.8, 1.0 Hz, 1H), 4.17 (s, 2H), 3.31 (s, 6H).

来源