Tris(hydroxymethyl)aminomethane → HCID 178514074, compound

Participants

Reaction Steps

To 3-(5-morpholin-4-ylmethyl-1H-benzimidazol-2-yl)-1H-pyrazol-ylamine (Example 1E) (100 mg, 0.33 mmol), in THF (2 ml), was added 4-fluorophenyl isocyanate and the mixture was stirred for about 16 hours at room temperature. Resin-supported tris-amine (800 mg, 4 mmol/g) was added and the mixture agitated for a further 4 hours. The resin was removed by filtration, the filtrate was treated with 1N KOH (2 ml, MeOH:THF; 1:3) and the solution stirred for approximately 16 hours. The mixture was then partitioned between EtOAc and H2O. The aqueous layer was further extracted with EtOAc and then the combined organic fractions washed with brine, dried (MgSO4) and evaporated to dryness. The crude solid was dissolved in DCM and triturated with hexanes to give a solid which was collected by filtration. The solid was purified by flash column chromatography [SiO2, EtOAc-MeOH (90:10)] to give 1-(4-fluorophenyl)-N-[3-(5-morpholin-4-ylmethyl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-urea (30 mg, 20%) as a yellow solid (LC/MS (acidic method): Rt 2.01 min, [M−H+]− 434).

Provenance & Evidence