反应详情

温度

120 °C

A mixture of 9-bromo-2-pyridin-3-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (35 mg, 0.10 mmol), 1-tert-butylpiperidine-4-thiol (53 mg, 0.30 mmol), Pd2(dba)3 (9 mg, 10 mol %), XantPhos (12 mg, 20 mol %) and DIPEA (72 μL, 0.41 mmol) in dioxane (2 mL) was purged with argon and heated at 120° C. for 40 min, then 130° C. for 1 h and 140° C. for 1 h using microwave irradiation. 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 0-20% 2M NH3/MeOH in EtOAc then C18, gradient 2-20% 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 affording 153 as an off-white solid (6 mg, 15%). LCMS: RT 2.42 min [M+H]+ 435.1. 1H NMR (CDCl3, 400 MHz): δ 9.03-9.02 (1H, m), 8.75-8.72 (1H, m), 8.51 (1H, dd, J=4.82, 1.67 Hz), 8.21 (1H, d, J=7.88 Hz), 7.35-7.33 (3H, m), 6.99 (1H, d, J=8.26 Hz), 4.52-4.50 (2H, m), 4.46-4.44 (2H, m), 3.03-2.98 (2H, br m), 2.20 (2H, br m), 2.06-1.94 (3H, br m), 1.66-1.62 (2H, br m), 1.06 (9H, br m)

1. customwas purged with argon
2. wait140° C. for 1 h using
3. custommicrowave irradiation
4. washwas washed with MeOH
5. washthe product eluted with 2M NH3/MeOH
6. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-20% 2M NH3/MeOH in EtOAc
7. washwas washed with MeOH
8. washthe product eluted with 2M NH3/MeOH affording 153 as an off-white solid (6 mg, 15%)