2,2-Dimethyl-1,3-dioxane-4,6-dione → 4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(pyridin-3-yl)-5-(thiophen-3-yl)-3,4-dihydropyridin-2(1H)-one

Participants

Reaction Steps

A mixture of 1-(pyridin-3-yl)-2-(thiophen-3-yl)ethanone (Intermediate 1, see Example 18 for synthesic description of all intermediates) (230 mg, 1.1 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (296 mg, 1.4 mmol), meldrum's acid (202 mg, 1.4 mmol) and AcONH4 (108 mg, 1.4 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 2 (60 mg, 12%). 1H NMR (MeOD 400 MHz): δ 8.70 (d, J=5.2 Hz, 1H), 8.67 (s, 1H), 8.30 (d, J=8.0 Hz, 1H), 7.90-7.62 (m, 1H), 7.72-7.60 (m, 1H), 7.27-7.24 (m, 2H), 6.94-6.92 (m, 1H), 6.58 (d, J=4.8 Hz, 1H), 4.20-4.11 (m, 3H), 3.30-3.25 (m, 1H), 2.79-2.74 (dd, J=16.2, 3.2 Hz, 1H), 1.45 (t, J=6.8 Hz, 3H). MS (ESI): m/z 438.3 [M+1]+.

Provenance & Evidence