反应详情

温度

75 °C

A suspension of 3-bromo-4-hydroxy-N-(4-(trifluoromethoxy)phenyl)benzamide (50 mg, 0.133 mmol), 2-bromoethyl acetate (21.94 μL, 0.199 mmol) and powdered K2CO3 (92 mg, 0.665 mmol) in acetone (500 μL) was stirred at 75° C. for 16 h and the solvent was evaporated off under reduced pressure. The residue, together with pyrimidin-5-ylboronic acid (57.61 mg, 0.465 mmol), Pd(PPh3)2Cl2 (18.66 mg, 0.026 mmol) water (125 μL), EtOH (62 μL) and DME (550 μL) were added to a vial, which was sealed, evacuated/purged with argon and the RM stirred at 80° C. for 20 h. The RM was diluted with THF (3 mL) then stirred with Si-Thiol (Silicycle, 105 mg, 0.133 mmol) for 2 h, filtered and the filtrate was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 12 g, cyclohexane/EtOAc from 30% to 95% EtOAc) to afford the acylated product, which was treated with aq. 4 M NaOH (138 μL, 0.552 mmol) and MeOH (250 μL) at and stirred at RT for 4 h. The RM was acidified with TFA and purified by preparative HPLC (Condition 8, 50% for 0.2 min then 50% to 80% in 14 min) to afford the title compound as a beige solid. UPLC-MS (Condition 1) tR=2.24 min, m/z=420.0 [M+H]+, m/z=418 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.64-3.82 (m, 2H) 4.21 (t, J=4.6 Hz, 2H) 4.91 (t, J=5.4 Hz, 1H) 7.32-7.41 (m, 3H) 7.88 (d, J=9.0 Hz, 2H) 8.07 (dd, J=8.8, 2.2 Hz, 1H) 8.12 (d, J=2.2 Hz, 1H) 9.13 (s, 2H) 9.18 (s, 1H) 10.32 (s, 1H).

1. customthe solvent was evaporated off under reduced pressure
2. customwas sealed
3. customevacuated/purged with argon
4. stirringthe RM stirred at 80° C. for 20 h
5. additionThe RM was diluted with THF (3 mL)
6. filtrationfiltered
7. customthe filtrate was evaporated off under reduced pressure
8. customto give the crude product which
9. customwas purified by flash chromatography (Silica gel column, 12 g, cyclohexane/EtOAc from 30% to 95% EtOAc)
10. customto afford the acylated product, which
11. stirringstirred at RT for 4 h
12. custompurified by preparative HPLC (Condition 8, 50% for 0.2 min