反应详情

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 6.2, 1 g, 2.53 mmol), pyrrolidine (0.544 g, 5.06 mmol), DIPEA (1.325 mL, 7.58 mmol) and iPrOH (2.53 mL) were added to a MW vial and subjected to MW irradiation at 140° C. for 1 h. The mixture was treated with aqueous HCl (40 mL of 0.5 M) was added and extracted with EtOAc The combined extracts were washed with 0.5 M HCl (40 mL) and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue was crystallized from cyclohexane/EtOAc to yield the title compound as an off-white solid. UPLC-MS (Condition 3) tR=1.34 min, m/z=430.1/432.1 [M+H]+, m/z=428.3/430.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.76-2.01 (m, 4H) 3.60-3.80 (m, 4H) 7.33 (d, J=8.20 Hz, 2H) 7.72-7.91 (m, 2H) 8.32 (d, J=1.95 Hz, 1H) 8.66 (d, J=1.95 Hz, 1H) 10.20 (s, 1H).

1. customsubjected to MW irradiation at 140° C. for 1 h
2. additionwas added
3. extractionextracted with EtOAc The combined extracts
4. washwere washed with 0.5 M HCl (40 mL) and brine
5. dry with materialdried over Na2SO4
6. customthe solvent was evaporated off under reduced pressure
7. customto give a residue
8. customwas crystallized from cyclohexane/EtOAc