反应详情

温度

80 °C

A mixture of 9-bromo-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (750 mg, 1.91 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-1H-pyrazole (550 mg, 2.10 mmol), PdCl2dppf.DCM (156 mg, 0.19 mmol) and Cs2CO3 (1.55 g, 4.77 mmol) in dioxane (12 mL) and H2O (3 mL) was purged with argon and heated at 80° C. for 18 h. Further 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-1H-pyrazole (225 mg, 1.05 mmol) and PdCl2dppf.DCM (78 mg, 0.09 mmol) were added and the mixture heated at 85° C. for a further 24 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-5% MeOH in DCM) affording 9-Bromo-2-(3-trifluoromethyl-1H-pyrazol-4-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene as a white solid (20 mg, 3%). LCMS: RT 4.42 min [M+H]+ 399.0 and 401.0. 1H NMR (CDCl3, 400 MHz): δ 13.65 (1H, s), 8.57 (1H, d, J=2.61 Hz), 8.30 (1H, s), 7.43-7.42 (2H, m), 7.00 (1H, d, J=8.71 Hz), 4.52-4.45 (4H, m)

1. temperaturethe mixture heated at 85° C. for a further 24 h
2. washwas washed with MeOH
3. washthe product eluted with 2M NH3/MeOH
4. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-5% MeOH in DCM)