反应详情

温度

80 °C

DMF (0.13 mL) and SOCl2 (0.734 mL, 10.05 mmol) were added to a mixture of 6-chloro-5-iodonicotinic acid (1.00 g, 3.35 mmol) and 4-(trifluoromethoxy)aniline (0.623 mg, 3.52 mmol) in toluene (7 mL) and the RM was stirred at 80° C. for 1 h. The solvent was evaporated off under reduced pressure and under argon the residue was dissolved in THF (7.00 mL) and DIPEA (1.17 mL, 6.7 mmol), cooled to −15° C. treated dropwise with a solution of 4-(trifluoromethoxy)aniline (0.476 mL, 3.52 mmol) in THF (7.00 mL) and stirred at RT for 1 h. The solvent was evaporated off under reduced pressure and the residue treated with aq. 1N HCl (30 mL) and extracted with TBME (100 mL). The combined extracts were washed with sat. aq. Na2CO3 (30 mL) and brine (30 mL), dried over Na2SO4 and the solvent was evaporated off under reduced pressure until crystallization commenced. The product was triturated with n-heptane, filtered and dried to afford the title compound as an off-white solid. HPLC (Condition 4) tR=6.36 min, UPLC-MS (Condition 3) tR=1.23 min, m/z=441.1 [M−H]−.

1. customThe solvent was evaporated off under reduced pressure and under argon the residue
2. dissolutionwas dissolved in THF (7.00 mL)
3. stirringstirred at RT for 1 h
4. customThe solvent was evaporated off under reduced pressure
5. additionthe residue treated with aq. 1N HCl (30 mL)
6. extractionextracted with TBME (100 mL)
7. washThe combined extracts were washed with sat. aq. Na2CO3 (30 mL) and brine (30 mL)
8. dry with materialdried over Na2SO4
9. customthe solvent was evaporated off under reduced pressure until crystallization
10. customThe product was triturated with n-heptane
11. filtrationfiltered
12. customdried