反应详情

A solution of 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (0.252 mmol) in dioxane (1.5 mL) was treated with 1-(4-bromophenyl)-1H-pyrrole (0.252 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (10 mg), and 2M aq potassium carbonate (0.756 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 resulting organic phase was treated with Si-Thiol (Silicycle, 20 mg), dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by reverse phase HPLC (35-65% acetonitrile/water+0.1% NH4OH). The resulting product was purified by silica gel chromatography (0-8% methanol/dichloromethane) to afford the title compound as an amorphous white solid (42%). MS(ES)+ m/e 454.1 [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. additionThe resulting organic phase was treated with Si-Thiol (Silicycle, 20 mg)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude residue was purified by reverse phase HPLC (35-65% acetonitrile/water+0.1% NH4OH)
11. customThe resulting product was purified by silica gel chromatography (0-8% methanol/dichloromethane)