反应详情

3-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2,4-dioxoimidazolidin-1-yl)methyl)benzoic acid (100 mg, 0.24 mmol) (example 10-8), methylamaine hydrochloride (67 mg, 1 mmol), triethylamine (155 mg, 1.5 mmol), and EDC (57 mg, 0.3 mmol) in acetonitrile (3 mL) were irradiated in the microwave reactor at 80° C. for 10 minutes. The reaction was cooled, diluted with aqueous 1N HCl (100 mL) and extracted with ethyl acetate (3×, 75 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The crude product was dissolved in MeOH (3 mL) and purified by reversed phase HPLC (5 to 95% acetonitrile in H2O: 25 minute gradient) to afford 3-((3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-2,4-dioxoimidazolidin-1-yl)methyl)-N-methylbenzamide (25 mg, 25%) as white solid. MS M+H calculated 423.17. Found 423.2. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.14 μM.

1. temperatureThe reaction was cooled
2. extractionextracted with ethyl acetate (3×, 75 mL)
3. dry with materialThe combined organic extracts were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe crude product was dissolved in MeOH (3 mL)
7. custompurified by reversed phase HPLC (5 to 95% acetonitrile in H2O: 25 minute gradient)