反应详情

A mixture of 1-(1-methyl-1H-pyrazol-4-yl)-2-(thiophen-3-yl)ethanone (Intermediate 3) (150 mg, 0.73 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (185 mg, 0.87 mmol), meldrum's acid (125 mg, 0.87 mmol) and AcONH4 (84 mg, 1.1 mmol) in AcOH (3 mL) was refluxed under N2 overnight. The mixture was concentrated under reduced pressure and the residue was purified by prep-HPLC (0.1% TFA as additive) to give Compound 4 as yellow solid (20 mg, 6%). 1H NMR (DMSO-d6, 400 MHz): δ 10.20 (s, 1H), 9.43 (s, 1H), 7.62 (s, 1H), 7.42-7.36 (m, 2H), 7.19-7.11 (m, 1H), 7.06 (s, 2H), 6.70-6.68 (m, 1H), 4.11-4.03 (m, 2H), 3.95-3.92 (m, 1H), 3.77 (s, 3H), 3.08 (dd, J=16.4, 7.6 Hz, 1H), 2.60-2.52 (m, 1H), 1.34 (t, J=6.8 Hz, 3H). MS (ESI): m/z 440.9 [M+1]+.

1. temperaturewas refluxed under N2 overnight
2. concentrationThe mixture was concentrated under reduced pressure
3. customthe residue was purified by prep-HPLC (0.1% TFA as additive)