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 (400 mg, 1.07 mmol), 1-isopropylpiperidine-4-thiol (340 mg, 2.14 mmol), Pd2(dba)3 (50 mg, 5 mol %), XantPhos (61 mg, 10 mol %) and DIPEA (0.745 mL, 4.28 mmol) in dioxane (10 mL) was purged with nitrogen and then heated at 120° C. for 1 h using microwave irradiation. The reaction mixture was diluted with DCM (200 mL) and purified by column chromatography (Si-PCC, 0-13% MeOH in DCM) then (C18, 20-45% MeOH in 0.003M HCl/H2O). The product containing fractions were combined and concentrated in vacuo and the resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 0.5M NH3/MeOH. The basic fractions were concentrated under reduced pressure affording 176 as a colorless solid (437 mg, 90%). LCMS: RT 3.01 min [M+H]+ 453.3. 1H NMR (MeOD, 400 MHz): δ 8.54 (1H, d, J=2.36 Hz), 7.93 (1H, s), 7.77 (1H, s), 7.36 (1H, dd, J=8.49, 2.37 Hz), 7.02 (1H, d, J=8.49 Hz), 5.96-5.86 (1H, m), 4.55-4.46 (4H, m), 3.11-3.05 (1H, m), 2.94-2.84 (2H, m), 2.75-2.63 (1H, m), 2.28 (2H, t, J=11.32 Hz), 2.05-1.95 (2H, m), 1.69-1.53 (8H, m), 1.04 (6H, d, J=6.57 Hz)

1. customwas purged with nitrogen
2. custommicrowave irradiation
3. additionThe reaction mixture was diluted with DCM (200 mL)
4. custompurified by column chromatography (Si-PCC, 0-13% MeOH in DCM)
5. additionThe product containing fractions
6. concentrationconcentrated in vacuo
7. washwas washed with MeOH
8. washthe product eluted with 0.5M NH3/MeOH
9. concentrationThe basic fractions were concentrated under reduced pressure