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 (100 mg, 0.27 mmol), 1-tert-butylpiperidine-4-thiol (120 mg, 0.69 mmol), Pd2(dba)3 (24 mg, 10 mol %), XantPhos (31 mg, 20 mol %) and DIPEA (186 μL, 1.07 mmol) in dioxane (3 mL) was purged with argon and heated at 120° C. for 40 min using microwave irradiation. The reaction mixture was diluted with DCM and purified by column chromatography (Si-PCC, gradient 0-20% MeOH in DCM then C18, gradient 20-50% MeOH in H2O). The resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The residue was triturated with Et2O affording 139 as a white solid (16 mg, 51%). LCMS: RT 3.11 min [M+H]+ 467.4. 1H NMR (DMSO, 400 MHz): δ 8.54 (1H, d, J=2.35 Hz), 7.94 (1H, d, J=0.67 Hz), 7.77 (1H, s), 7.36 (1H, dd, J=8.49, 2.37 Hz), 7.02 (1H, d, J=8.48 Hz), 5.92-5.91 (1H, m), 4.55-4.49 (4H, m), 3.06-3.04 (3H, m), 2.30 (2H, t, J=11.23 Hz), 2.08-1.96 (2H, m), 1.65-1.64 (2H, m), 1.58 (6H, d, J=6.65 Hz), 1.08 (9H, s)

1. customwas purged with argon
2. custommicrowave irradiation
3. additionThe reaction mixture was diluted with DCM
4. custompurified by column chromatography (Si-PCC, gradient 0-20% MeOH in DCM
5. washwas washed with MeOH
6. washthe product eluted with 2M NH3/MeOH
7. customThe residue was triturated with Et2O affording 139 as a white solid (16 mg, 51%)