反应详情

温度

130 °C

A mixture of 3-bromo-4-fluoro-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 1.2, 100 mg, 0.264 mmol), thiazole (113 mg, 1.322 mmol), KOAc (130 mg, 1.322 mmol) and Pd(OAc)2 (0.297 mg, 1.322 μmol) were added to a vial, which was sealed and evacuated/purged with argon. DMA (0.81 mL) was added and the mixture was stirred at 130° C. for 20 h. The RM was diluted with THF (3 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 9.18 mg, 0.013 mmol) and filtered off. The filtrate was poured onto 1 M HCl (40 mL) and extracted 3 times with TBME. The combined extracts were washed 3 times with 1M HCl, sat. NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc from 10% to 40% EtOAc) to yield the title compound as an off-white solid. UPLC-MS (Condition 1) tR=2.80 min, m/z=383.0 [M+H]+, m/z=381.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.40 (m, J=8.31 Hz, 2H) 7.58 (dd, J=10.76, 8.80 Hz, 1H) 7.83-7.97 (m, 2H) 8.02 (ddd, J=8.62, 4.95, 2.32 Hz, 1H) 8.40 (dd, J=7.21, 2.32 Hz, 1H) 8.49 (s, 1H) 9.28 (s, 1H) 10.54 (s, 1H).

1. additionwere added to a vial, which
2. customwas sealed
3. customevacuated/purged with argon
4. additionDMA (0.81 mL) was added
5. additionThe RM was diluted with THF (3 mL)
6. filtrationfiltered off
7. additionThe filtrate was poured onto 1 M HCl (40 mL)
8. extractionextracted 3 times with TBME
9. washThe combined extracts were washed 3 times with 1M HCl, sat. NaHCO3 and brine
10. dry with materialdried over Na2SO4
11. customthe solvent was evaporated off under reduced pressure
12. customto give a crude product which
13. customwas purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc from 10% to 40% EtOAc)