反应详情

To a microwave vial was added 1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(4-piperazin-1-ylphenyl)-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide hydrochloride (8-3) (0.028 g, 0.059 mmol), HATU (0.029 g, 0.077 mmol), isoxazole-3-carboxylic acid (0.0087 g, 0.077 mmol), NMP (1 mL), and finally DIPEA (0.060 mL, 0.344 mmol). The reaction mixture was then stirred at room temperature for 1 hour. The crude reaction mixture was then diluted with methanol, then filtered. Purification of crude reaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 10% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water) to give 1-[(2,2-difluorocyclopropyl)methyl]-5-{4-[4-(isoxazol-3-ylcarbonyl)piperazin-1-yl]phenyl}-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (34-1) as a tan solid. HRMS (M+H)+: observed=531.1613, calculated=531.1621.

1. customThe crude reaction mixture
2. filtrationfiltered
3. customPurification of crude
4. customreaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 10% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water)