反应详情

To a solution of 1.00 g (2.15 mmol) 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide in 5.70 ml dioxane was added 0.31 g (2.58 mmol) 2-chloro-3-methylpyrazine, 0.014 mg (0.052 mmol) tricyclohexylphosphine, 0.020 g (0.022 mmol) Pd2dba3, and 2.88 mL (3.66 mmol) 1.7M potassium phosphate. The resulting suspension was degassed for 10mins. After 30 min in the microwave at 150° C., the reaction mixture was cooled, extracted with ethyl acetate, and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (silica gel, linear gradient 30-100% EtOAc:hexane) followed by purification by reverse phase chromatography afforded 0.68 g (73.3%) 2-[4-(3-methylpyrazin-2-yl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide. 1H NMR (CDCl3, 400 MHz) 8.49 (d, 1H, J=2.20 Hz); 8.45 (d, 1H, J=2.38 Hz); 8.21 (d, 1H, J=2.39 Hz); 7.57 (d, 2H, J=8.24 Hz); 7.41 (d, 2H, J=7.83 Hz); 7.24-7.17 (m, 2H); 6.73 (br d, 1H, J=7.33 Hz); 5.13 (m, 1H); 4.38 (q, 2H, J=8.05 Hz); 3.67 (s, 2H); 2.65 (s, 3H); 1.41 (d, 3H, J=6.77). FIRMS (ES) exact mass calcd for C22H21F3N4O2: 431.1689, Found: 431.1690. FLIPR alpha1I IP=24 nM.

1. customThe resulting suspension was degassed for 10mins
2. temperaturethe reaction mixture was cooled
3. extractionextracted with ethyl acetate
4. washwashed with brine
5. dry with materialThe organic layer was dried over NaSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification by flash chromatography (silica gel, linear gradient 30-100% EtOAc:hexane)
9. customfollowed by purification by reverse phase chromatography