Dimethylformamide → HCID 86724391, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 1-(4-chlorophenyl)-5-cyclobutyl-pyrazole-4-carboxylic acid (4.0 g, 14.4 mmol) in CH2Cl2 (100 mL) was added oxalyl chloride (3.78 mL, 43.4 mmol) and DMF (0.06 mL). After 2 h at room temperature, the reaction mixture was concentrated in vacuo, re-dissolved in 40 mL of acetone, and added to a 0° C. solution of NaN3 (3.75 g, 57.8 mmol) in H2O (40 mL). Brine (150 mL) and EtOAc (350 mL) were then added. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was stirred in 100 mL of toluene at 95° C. for 1 h, cooled to room temperature, and then treated with 150 mL of 6 M aqueous HCl at 110° C. for 1 h. After cooling to room temperature the mixture was basified with dilute NH4OH and extracted with EtOAc (500 mL). The organic layer was separated, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography (SiO2, 0-100% EtOAc/CH2Cl2 gradient elution) to yield 1-(4-chlorophenyl)-5-cyclobutyl-pyrazol-4-amine (2.9 g, 81% yield).

Provenance & Evidence