反应详情

To a solution of 2-bromo-1-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)ethanone (Example 26, Step 2) (0.413, 1.11 mmol) in ethanol (10 mL) in a 25 mL round bottom flask was added N-(4-cyanophenyl)thiourea (0.207 g, 1.17 mmol). The solution was heated to reflux (24 hours) and the reaction was cooled to room temperature. The resulting suspension was concentrated in vacuo, suspended in methylene chloride (100 mL) and washed with sodium carbonate solution (10%, 3×20 mL), brine (1×20 mL), dried over sodium sulfate, filtered and concentrated yielding a solid. This solid was flash chromatographed (1:1, hexane:ethyl acetate with 1% acetic acid). The resulting product was recrystallized from methylene chloride and isooctane yielding 2-(4-cyanophenylamino)-4-(4-fluorophenyl)-5-(4-methylsulfonylphenyl)thiazole (0.266 g, 53%) as a pale yellow solid: mp 273°-274° C.; 1HNMR (DMSO d6) 400 mHz 10.98 (s, 1 H), 7.86 (d, J=8.32 Hz, 2 H), 7.83 (d, J=9.05 Hz, 2 H), 7.76 (d, J=8.80 Hz, 2 H), 7.55-7.47 (m, 4 H), 7.21 (t, J=8.80 Hz, 2 H), 3.22 (s, 3 H); MS m/z 450 (M+H). HRMS Δ=2.6 mmu.

1. temperatureThe solution was heated
2. temperatureto reflux (24 hours)
3. concentrationThe resulting suspension was concentrated in vacuo
4. washwashed with sodium carbonate solution (10%, 3×20 mL), brine (1×20 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customyielding a solid
9. customchromatographed (1:1, hexane:ethyl acetate with 1% acetic acid)
10. customThe resulting product was recrystallized from methylene chloride and isooctane