反应详情

A solution of 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (0.245 mmol) in dioxane (1.5 mL) was treated with 4-bromo-2-methylbenzonitrile (0.245 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (10 mg), and 2M aq potassium carbonate (0.736 mmol). The reaction mixture was purged with nitrogen, sealed, and irradiated in a microwave (Biotage Initiator) at 150° C. for 15 min. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH˜4 using 1N aq HCl and was extracted with dichloromethane. The organic layer was dried over magnesium sulfate, treated with Si-Thiol (Silicycle, 20 mg), filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (20-50% acetonitrile/water+0.1% NH4OH) to afford the title compound as an amorphous off-white solid (57%). MS(ES)+ m/e 446.2 [M+H]+.

1. customThe reaction mixture was purged with nitrogen
2. customsealed
3. customirradiated in a microwave (Biotage Initiator) at 150° C. for 15 min
4. additionwas diluted with water (50 mL)
5. extractionwas extracted with dichloromethane
6. dry with materialThe organic layer was dried over magnesium sulfate
7. additiontreated with Si-Thiol (Silicycle, 20 mg)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude residue was purified by reverse phase HPLC (20-50% acetonitrile/water+0.1% NH4OH)