4-Methylmorpholine → HCID 21899148, compound

Participants

Reaction Steps

N-[1-(3-fluorophenyl)-5-piperidino-1-ylmethyl-1H-benzoimidazol-2-yl]-3-trifluoromethyl-benzamide: 500 mg 1-(3-fluorophenyl)-5-piperidin-1-ylmethyl-1H-benzoimidazol-2-ylamine (1.54 mmol, 1.0 equiv) was combined in a flask with 877 mg O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 2.32 mmol, 1.5 equiv), 440 mg 3-trifluoromethylbenzoic acid (2.32 mmol, 1.5 equiv) and 312 mg 1-hydroxybenzotriazole hydrate (HOBT, 2.32 mmol, 1.5 equiv) followed by the addition of 12 mL DMF and 254 μL N-methylmorpholine (NMM, 2.32 mmol, 1.5 equiv). The solution was allowed to stir for 24 h and then diluted with sat. Na2HCO3. The solution was extracted (2×10% MeOH/CH2Cl2), washed (1×brine), dried (NaSO4) and concentrated under reduced pressure. Purification by flash chromatography (SiO2, 5% MeOH/CH2Cl2) gave 0.2 g of the product as a tan solid (0.2 mmol). 1H NMR (DMSO-d6, 400 MHz) 13.0 (s, 1H), 8.35 (s, 1H), 8.30 (d, J=7.6 Hz, 1H), 7.88 (d, J=7.6 Hz, 1H), 7.72 (m, 3H), 7.62 (m, 2H), 7.47 (t, J=7.6 Hz, 1H), 7.22 (broad s, 2H), 3.55 (s, 2H), 2.38 (broad s, 4H), 1.5 (m, 6H).

Provenance & Evidence