Diisopropylethylamine → HCID 178522267, compound

Participants

Reaction Steps

To a solution of 5-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid (Example 105, 250 mg, 0.57 mmol) and diisopropylethylamine (350 μL, 2.0 mmol)) in dimethylformamide (5 mL) was added a mixture of 2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,3-triazol-4-yl)ethanamine and 2-(2-((2-(trimethylsilyl)ethoxy)methyl)-2H-1,2,3-triazol-4-yl)ethanamine and 2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,3-triazol-5-yl)ethanamine (Preparation 65, 210 mg, 0.84 mmol). The mixture was stirred for 5 minutes before the addition of HATU (220 mg, 0.57 mmol). The reaction was stirred at room temperature for 18 hours and concentrated in vacuo. The residue was partitioned between EtOAc (80 mL) and dilute aqueous sodium hydrogen carbonate solution (80 mL) with saturated aqueous sodium chloride solution (10 mL). The organic layer was collected, dried over anhydrous sodium sulphate and concentrated in vacuo. The residue was dissolved in DCM (20 mL) and treated with TFA (20 mL) with stirring at room temperature for 18 hours. After concentration in vacuo, the residue was partitioned between DCM (80 mL) with MeOH (4 mL) and dilute aqueous sodium hydrogen carbonate solution (50 mL). The organic layer was collected, dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 95:5:0.5 to 90.10:1 DCM:MeOH:NH3 followed by dissolving in hot MeCN (15 mL). The solution was cooled and decanted to afford a residue that was azeotroped with toluene and water to afford the title compound (31 mg, quant.).

Provenance & Evidence