反应详情

温度

80 °C

A microwave vial was charged with an approximately 1:1 mixture of 4-(8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-2,5-dimethyl-2,4-dihydro-[1,2,4]triazol-3-one and 4-(8-iodo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-2-yl)-2,5-dimethyl-2,4-dihydro-[1,2,4]triazol-3-one (41 mg), 2-methyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-propan-2-ol (33 mg, 0.13 mmol), PdCl2(dppf)2.DCM (3.5 mg, 0.004 mmol), cesium carbonate (68 mg, 0.21 mmol), THF (1 mL) and water (0.2 mL). The vial was sealed and the mixture evacuated and purged with argon (×3). The reaction mixture was heated at 80° C. for 17 hours then a further 2-methyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-propan-2-ol (15 mg) and PdCl2(dppf)2.DCM (4 mg) were added, the vial was re-filled with argon as before and stirring at 80° C. was continued for a further 20 hours. After cooling the reaction mixture was concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 0-4% MeOH in DCM) to give 473 as a white solid (12 mg, 27%). LCMS: RT=4.14 min, [M+H]+=453. 1H NMR δ (ppm) (DMSO-d6): 8.14 (1H, d, J=8.26 Hz), 8.08 (1H, s), 7.87 (1H, s), 7.33 (1H, dd, J=8.26, 1.84 Hz), 7.22 (1H, d, J=1.82 Hz), 4.68 (1H, s), 4.31 (2H, t, J=5.01 Hz), 3.98 (2H, s), 3.35 (3H, s), 3.28 (2H, m), 2.65 (3H, s), 1.04 (6H, s)

1. customThe vial was sealed
2. customthe mixture evacuated
3. custompurged with argon (×3)
4. additionDCM (4 mg) were added
5. additionthe vial was re-filled with argon as before and
6. temperatureAfter cooling the reaction mixture
7. concentrationwas concentrated in vacuo
8. customThe resultant residue was purified by flash chromatography (SiO2, 0-4% MeOH in DCM)