反应详情

温度

120 °C

To a solution of 3-bromo-5-(tetrahydro-2H-pyran-4-yl)pyrazin-2-amine (154 mg, 0.418 mmol), (S)—N-(2-hydroxy-1-phenylethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (90 mg, 0.349 mmol), and PdCl2(dppf) (25.5 mg, 0.035 mmol) was added dioxane (2.3 mL) and 2 M Na2CO3 solution (1.163 mL). The reaction mixture was heated at the microwave synthesizer (120° C., 10 min). The reaction mixture was worked up with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered off, and concentrated in vacuo. The crude product was purified by prep HPLC. The pure fractions were combined, free-based with sodium carbonate solution, and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate, filtered off, and dried in vacuo. The pure solid was dissolved in MeCN/water (1:1, 6 mL) and lyophilized yielding (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-hydroxy-1-phenylethyl)benzamide as free base (46%). LCMS (m/z): 419.2 (MH+), 0.58 min; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.74 (d, J=12 Hz, 1H), 7.99 (d, J=8 Hz, 2H), 7.88 (s, 1H), 7.79 (d, J=12 Hz, 2H), 7.37 (d, J=8 Hz, 2H), 7.29 (m, 2H), 7.22 (m, 1H), 5.99 (bs, 1H), 5.07 (m, 1H), 3.91 (m, 2H), 3.67 (m, 2H), 3.41 (m, 2H), 2.82 (m, 1H), 1.72 (m, 4H).

1. washThe organic layer was washed with water and brine
2. dry with materialdried over anhydrous sodium sulfate
3. filtrationfiltered off
4. concentrationconcentrated in vacuo
5. customThe crude product was purified by prep HPLC
6. extractionextracted with EtOAc
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. filtrationfiltered off
9. customdried in vacuo
10. dissolutionThe pure solid was dissolved in MeCN/water (1:1, 6 mL)