反应详情

温度

80 °C

(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylphenyl)methanol (39-1) (7.3 g, 18.4 mmol, 1.0 eq) was dissolved in NMP (90 mL) and triethylamine (7.7 mL, 55.2 mmol, 3.0 eq) was added followed by mesyl chloride (1.6 mL, 20.3 mmol, 1.1 eq). After 20 minutes, 1-acetylpiperazine (3.3 g, 25.7 mmol, 2.0 eq) and DIPEA (9.0 mL, 51.3 mmol, 3.0 eq) were added. The resulting mixture stirred at 80° C. for 2 hours minutes. The mixture was cooled, diluted with EtOAc (300 mL), washed with sodium bicarbonate (50 mL), water (6×50 mL) and brine (50 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (330 g SiO2, 0-20% IPA in DCM) to afford 1-[4-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzyl)piperazin-1-yl]ethanone (39-2) as an off-white solid. 1H NMR (400 MHz, CD3OD): δ 7.36 (d, J=8.0 Hz, 1 H); 7.35 (s, 1 H); 7.25 (s, 2 H); 7.08 (d, J=8.0 Hz, 1 H); 3.97 (d, J=6.8 Hz, 2 H); 3.56 (s, 2 H); 3.54 (dt, J=5.2, 20.4 Hz, 4 H); 3.38 (s, 3 H); 2.46 (dt, J=5.2, 18.8 Hz, 4 H); 2.35 (s, 3 H); 2.21 (m, 1 H); 2.07 (s, 3 H); 1.67 (m, 1 H); 1.43 (m, 1 H). HRMS m/z (M+H) 506.2029 found, 506.2032 required.

1. temperatureThe mixture was cooled
2. washwashed with sodium bicarbonate (50 mL), water (6×50 mL) and brine (50 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude residue was purified by flash chromatography (330 g SiO2, 0-20% IPA in DCM)