反应详情

温度

150 °C

A microwaveable vial was charged with 4-(4-bromo-2-methylphenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (100 mg, 0.247 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (63.2 mg, 0.259 mmol), PdCl2(dppf) (9.03 mg, 0.012 mmol), K2CO3 (85 mg, 0.617 mmol), 1,4-dioxane (3 mL) and water (1 mL). The reaction was purged with nitrogen, sealed and heated in a microwave reactor at 150° C. for 30 min (LCMS indicated complete conversion of starting material to desired product). The reaction mixture was concentrated under reduced pressure and the residue was dissolved in DMSO, filtered through a syringe filter and purified by reverse phase HPLC (Gilson, YMC-Pack ODS-A C18 5 μm 75×30 mm column, 10-90% MeCN/water+0.1% TFA, 3×1 mL injections). The appropriate fractions were concentrated to dryness and the residue was diluted with water (10 mL) and adjusted to pH 5 with conc. NH4OH. The resulting precipitate was collected by filtration and dried to constant weight under vacuum to provide the title product (40 mg, 0.090 mmol, 36.6% yield) as a white solid. MS(ES)+ m/e 443.1 [M+H]+.

1. customThe reaction was purged with nitrogen
2. customsealed
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. dissolutionthe residue was dissolved in DMSO
5. filtrationfiltered through a syringe
6. filtrationfilter
7. custompurified by reverse phase HPLC (Gilson, YMC-Pack ODS-A C18 5 μm 75×30 mm column, 10-90% MeCN/water+0.1% TFA, 3×1 mL injections)
8. concentrationThe appropriate fractions were concentrated to dryness
9. additionthe residue was diluted with water (10 mL)
10. filtrationThe resulting precipitate was collected by filtration
11. customdried to constant weight under vacuum