反应详情

A solution of 2-thiazol-4-yl-3H-benzoimidazol-5-ylamine (1-5, 100 mg, 0.46 mmol) in N,N-dimethylformamide (2 mL). The 1,1′-carbonyldiimidazole (CDI, 82 mg, 0.51 mmol) was added in one sum to the solution and was stirred for two hours. The 3-fluorophenethylamine (2-1, 72 uL, 0.56 mmol) was added to the reaction mixture via pipet and stirred to completion by LCMS analysis. The LCMS indicated that the dibenzimidazole urea was the by-product. The reaction mixture was partitioned between ethyl acetate and dilute sodium bicarbonate solution. The insoluble urea by-product was removed by vacuum filtration of the layers and the aqueous was extracted (3×10 mL) with ethyl acetate. The organic layer was washed twice with water, once with brine, separated, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting red solid was triturated in ethyl acetate/hexanes mixtures to afford the pure 1-[2-(3-fluoro-phenyl)-ethyl]-3-(2-thiazol-4-yl-3H-benzoimidazol-5-yl)-urea as a gray solid (2-77); 1H NMR (500 MHz, DMSO-d6) δ 12.72 (s, 1H), 9.31 (t, 1H, J=2.0 Hz), 8.52 (s, 1H), 8.34 (d, 1H, J=2.0 Hz), 7.87 (d, 1H, J=1.0 Hz), 7.47 (d, 1H, J=8.5 Hz), 7.35 (d, 1H, J=6.5 Hz), 7.11 (d, 2H, J=8.0 Hz), 7.04 (dt, 1H, J=8.5, 2.0 Hz), 6.96 (dd, 1H, J=8.5, 2.0 Hz), 6.06 (m, 1H), 3.38 (q, 2H, J=7.0 Hz), 2.80 (t, 2H, J=7.0 Hz).

1. stirringstirred to completion by LCMS analysis
2. customThe reaction mixture was partitioned between ethyl acetate and dilute sodium bicarbonate solution
3. customThe insoluble urea by-product was removed by vacuum filtration of the layers
4. extractionthe aqueous was extracted (3×10 mL) with ethyl acetate
5. washThe organic layer was washed twice with water, once with brine
6. customseparated
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe resulting red solid was triturated in ethyl acetate/hexanes mixtures