反应详情

To a 25-mL two-neck round bottom flask under argon was charged with 2-(3-(4-fluorobenzyl)-2-oxo-2,3-dihydro-1H-imidazol-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide (0.10 g, 0.24 mmol) and tetrahydrofuran (5 mL). Diethylzinc in hexanes (0.35 mL of 1 M solution, 0.35 mmol) was added slowly with a syringe. The solution was stirred and maintained at ambient temperature while diiodomethane (0.10 g, 0.35 mmol) was added slowly with a syringe. The reaction mixture was stirred at 60° C. for 8 hours and cooled in an ice-water bath, followed by the addition of saturated aqueous ammonium chloride (5 mL). The mixture was extracted with ethyl acetate (80 mL) and washed with saturated aqueous ammonium chloride (2×8 mL), water (3×8 mL), dried over sodium sulfate and filtered. The filtrate was concentrated and purified by preparative thin layer chromatography eluted with dichloromethane/methanol (20/1) to afford the title compound in 7% yield (7 mg). 1H NMR (300 MHz, CDCl3) δ 8.57 (br, 2H), 7.66-7.63 (m, 1H), 7.35-7.26 (m, 2H), 7.20-7.18 (m, 1H), 7.06-7.00 (m, 2H), 6.31-6.29 (m, 1H), 4.87 (br s, 2H), 4.74 (br s, 2H), 3.00 (br s, 2H), 2.39 (s, 3H), 0.92-0.81 (m, 2H); MS (ES+) m/z 437.9 (M+1).

1. additionwas added slowly with a syringe
2. stirringThe reaction mixture was stirred at 60° C. for 8 hours
3. temperaturecooled in an ice-water bath
4. extractionThe mixture was extracted with ethyl acetate (80 mL)
5. washwashed with saturated aqueous ammonium chloride (2×8 mL), water (3×8 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was concentrated
9. custompurified by preparative thin layer chromatography
10. washeluted with dichloromethane/methanol (20/1)