反应详情

温度

80 °C

(R,E)-6-(3-Hydroxypyrrolidin-1-yl)-5-(3-oxobut-1-en-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 3.1, 50 mg, 0.091 mmol) and toluene-4-sulfonic acid hydrazide (34.5 mg, 0.181 mmol) and EtOH (302 μL) were added to a MW vial, which was sealed and stirred at 80° C. for 1.5 h. The mixture was cooled to RT, NaOMe (17.15 mg, 0.318 mmol) was added and the RM was stirred at 80° C. for 48 h. Aq. The RM was acidified with aq. formic acid, filtered through a 0.2 μM PTFE membrane filter and purified by preparative HPLC (Condition 9, from 20% to 50% in 18 min) to yield the title compound as a white solid. UPLC-MS (Condition 1) tR=2.08 min, m/z=448.0 [M+H]+, m/z=446.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.79 (m, 1H) 1.78-1.90 (m, 1H) 2.29 (br. s, 3H) 2.98 (d, J=11.74 Hz, 1H) 3.25-3.37 (m, 2H) 3.40-3.53 (m, 1H) 4.21 (br. s, 1H) 4.83 (br. s, 1H) 6.13 (s, 1H) 7.33 (d, J=8.31 Hz, 2H) 7.86 (d, 2H) 8.01 (br. s, 1H) 8.71 (br. s, 1H) 10.15 (s, 1H) 12.57 (br. s, 1H).

1. customwas sealed
2. temperatureThe mixture was cooled to RT
3. stirringthe RM was stirred at 80° C. for 48 h
4. filtrationfiltered through a 0.2 μM PTFE membrane
5. filtrationfilter
6. custompurified by preparative HPLC (Condition 9, from 20% to 50% in 18 min)