反应详情

To a solution of 0.10 g (0.48 mmol) (4-pyrazin-2-ylphenyl)acetic acid in 2.00 ml of CH2Cl2 was added 0.17 g (0.58 mmol) of 2-[(1R)-1-ammonioethyl]-5-(2,2,2-trifluoroethoxy)pyridinium dichloride, 0.085 g (0.63 mmol) of HOAt, 0.12 g (0.63 mmol) of EDC, and 0.25 mL (1.44 mmol) of DIEA. After 1 h at room temperature, the reaction mixture was diluted with CH2Cl2, washed three times with water, and washed with brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (silica gel, linear gradient 50-100% EtOAc in hexanes) afforded 0.14 g (70%) of 2-(4-pyrazin-2-ylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide. 1H NMR (CD3OD, 400 MHz) 9.09 (d, J=1.46 Hz, 1H); 8.65 (t, J=1.74 Hz, 1H); 8.51 (d, J=2.57 Hz, 1H); 8.26 (d, J=3.02 Hz, 1H); 8.03 (d, J=8.15 Hz, 2H); 7.46 (d, J=8.15 Hz, 2H); 7.43 (dd, J=3.02, 8.70 Hz, 1H); 7.30 (d, J=8.70 Hz, 1H); 5.03 (quintet, J=6.96 Hz, 1H); 4.62 (q, J=8.34 Hz, 2H); 3.64 (s, 2H); 1.46 (d, 3H, J=6.96 Hz). HRMS (ES) [M+1]+calcd for C21H20F3N4O2: 417.1538, Found: 417.1523. FLIPR alpha1I IP=30 nM.

1. washwashed three times with water
2. washwashed with brine
3. dry with materialThe organic layer was dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification by flash chromatography (silica gel, linear gradient 50-100% EtOAc in hexanes)