Cesium carbonate → HCID 57422411, compound

Participants

Reaction Steps

2-(1H-pyrazol-4-yl)isoindoline-1,3-dione (example 9-1a) (1.5 g, 7 mmol), 4-(chloromethyl)-3,5-dimethylisoxazole (1.5 g, 10 mmol), and cesium carbonate (3.3 g, 10 mmol) were stirred in DMF (20 mL) at 80° C. for 3 hours. The reaction was cooled, diluted with H2O (150 mL), and extracted with ethyl acetate (3×, 75 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated on the rotovap. The solid product was triturated with ethyl acetate/hexanes (1/9) and re-crystallized from refluxing absolute ethanol (30 mL) to afford 2-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)isoindoline-1,3-dione (900 mg, 38%) as a bright, light yellow solid. 1H NMR (DMSO-d6, 400 MHz) 1.36 (d, 3H, δ J2.16 (s, 3H), 2.41 (s, 3H),=7.2 Hz), 5.22 (s, 2H), 7.81 (s, 1H), 7.91-7.83 (m, 4H), 8.21 (s, 1H). MS M+H calculated 323.11; found 323.1. Melting point: 170-171° C. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.18 μM.

Provenance & Evidence