1,1'-Carbonyldiimidazole → HCID 9999882, compound

Reaction equation

[S:1]1[CH:5]=[C:4]([C:6]2[NH:7][C:8]3[CH:14]=[C:13]([NH2:15])[CH:12]=[CH:11][C:9]=3[N:10]=2)[N:3]=[CH:2]1.[C:16]([N:23]1[CH:27]=[CH:26]N=C1)(N1C=CN=C1)=[O:17].[F:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=1)CCN>CN(C)C=O>[F:28][C:29]1[CH:37]=[C:36]([CH2:26][CH2:27][NH:23][C:16]([NH:15][C:13]2[CH:12]=[CH:11][C:9]3[N:10]=[C:6]([C:4]4[N:3]=[CH:2][S:1][CH:5]=4)[NH:7][C:8]=3[CH:14]=2)=[O:17])[CH:35]=[CH:31][CH:30]=1

Participants

Procedure

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).