反应详情

温度

150 °C

A microwave 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 (60.0 mg, 0.148 mmol), (4-fluorophenyl)boronic acid (20.71 mg, 0.148 mmol), PdCl2(dppf) (5.42 mg, 7.40 μmmol), K2CO3 (51.2 mg, 0.370 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. 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, 2×1 mL injections). The appropriate fractions were concentrated to remove a majority of the MeCN. The remaining aqueous mixture (product had oiled out) was extracted with two portions of dichloromethane. The combined dichloromethane layers were dried over Na2SO4, filtered, concentrated under reduced pressure and dried to constant weight under vacuum to provide the title product (36 mg, 0.086 mmol, 57.8% yield) as a yellow solid. MS(ES)+ m/e 421.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.75 (d, J=4.04 Hz, 1H), 7.75-7.86 (m, 2H), 7.73 (br. s., 1H), 7.58-7.66 (m, 1H), 7.42 (td, J=8.34, 4.29 Hz, 1H), 7.33 (t, J=8.84 Hz, 2H), 3.59-3.88 (m, 1H), 3.46-3.59 (m, 1H), 2.82-3.38 (m, 2H), 2.28-2.49 (m, 3H), 2.12-2.20 (m, 3H), 1.87-2.07 (m, 1H), 1.39-1.76 (m, 2H), 0.59-0.76 (m, 4H).

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, 2×1 mL injections)
8. concentrationThe appropriate fractions were concentrated
9. customto remove a majority of the MeCN
10. extractionwas extracted with two portions of dichloromethane
11. dry with materialThe combined dichloromethane layers were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customdried to constant weight under vacuum