反应详情

温度

120 °C

A mixture of 9-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene from Example 1 (100 mg, 0.267 mmol), 4-mercaptopiperidine-1-carboxylic acid tertbutyl ester (87 mg, 0.401 mmol), Pd2(dba)3 (13 mg, 5 mol %), XantPhos (15 mg, 10 mol %) and DIPEA (0.19 mL) in dioxane (3 mL) was purged with nitrogen and then heated at 120° C. for 1 h using microwave irradiation. The same process was repeated using a mixture of 9-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (400 mg, 1.068 mmol), 4-mercaptopiperidine-1-carboxylic acid tertbutyl ester (348 mg, 1.604 mmol), Pd2(dba)3 (50 mg, 5 mol %), XantPhos (61 mg, 10 mol %) and DIPEA (0.745 mL) in dioxane (10 mL). The two crude reaction mixtures were combined into DCM (200 mL) and purified by column chromatography (Si-PCC, gradient 0-7% MeOH in DCM) affording the title compound as an orange gum (1.27 g, quantitative). LCMS: RT 4.15 min [M+H]+ 511.3. (110174852)

1. customwas purged with nitrogen
2. custommicrowave irradiation
3. customThe two crude reaction mixtures
4. custompurified by column chromatography (Si-PCC, gradient 0-7% MeOH in DCM)