反应详情

温度

-30 °C

A solution of 1-isopropyl-3-methyl-1H-[1,2,4]triazole (in a 6:4 mixture with 1-isopropyl-5-methyl-1H-[1,2,4]triazole, 0.292 g, 1.4 mmol) in THF (5 mL) was cooled to −30° C. and treated with n-butyllithium (2.5M in hexanes, 0.56 mL, 1.40 mmol). Stirring was continued for 1 h maintaining the internal temperature between −30° C. and −20° C. The mixture was then cooled to −30° C. and a solution of zinc chloride (0.5M in THF, 1.66 mL, 0.83 mmol) was added over 2 min. The reaction mixture was then slowly warmed to RT over 1 h. A solution of 9-bromo-2-iodo-8-methyl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (404 mg, 1.0 mmol) in THF (5 mL) was added followed by Pd(PPh3)4 (58 mg, 0.128 mmol) and the reaction mixture was stirred at 60° C. under a nitrogen atmosphere for 18 h. After cooling to RT, volatiles were removed in vacuo and the residue was partitioned between EtOAc (300 mL) and water. The aqueous phase was further extracted with EtOAc (300 mL) and the combined organic layers were washed with water followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, eluent 100% EtOAc followed by gradient 1-10% MeOH in EtOAc) affording the title compound (0.168 g, 35%). LCMS: RT 3.71 min [M+H]+ 402.0/404.0. 110178153

1. temperaturemaintaining the internal temperature between −30° C. and −20° C
2. temperatureThe reaction mixture was then slowly warmed to RT over 1 h
3. stirringthe reaction mixture was stirred at 60° C. under a nitrogen atmosphere for 18 h
4. temperatureAfter cooling to RT
5. customvolatiles were removed in vacuo
6. customthe residue was partitioned between EtOAc (300 mL) and water
7. extractionThe aqueous phase was further extracted with EtOAc (300 mL)
8. washthe combined organic layers were washed with water
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customThe resulting residue was purified by column chromatography (Si-PCC, eluent 100% EtOAc followed by gradient 1-10% MeOH in EtOAc)