Ammonium Chloride → HCID 86692622, compound

Participants

Reaction Steps

2-Bromo-2-methylpropanoic acid ethyl ester (193 μl) was added to a suspension of N-[6-(4-cyanopiperidin-4-yl)pyridin-3-yl]-5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carboxamide (455 mg) described in Reference Example 169 and potassium carbonate (276 mg) in N,N-dimethylformamide (3.3 ml) and stirred at 50° C. for 12 hours. Then, 2-bromo-2-methylpropanoic acid ethyl ester (100 μl) and potassium carbonate (276 mg) were added and stirred at 50° C. for 5 hours and at 80° C. for 3 hours. Further, 2-bromo-2-methylpropanoic acid ethyl ester (100 μl) was added and stirred at 80° C. for 3 hours. Water was added to the reaction solution, the precipitated solid was purified with silica gel chromatography (chloroform/methanol) to give 2-{4-cyano-4-[5-({5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carbonyl}amino)pyridin-2-yl]piperidin-1-yl}-2-methylpropanoic acid ethyl ester (320 mg) as a white solid. MS (ESI) m/z: 570 (M+H)+. (2) Lithium borohydride (25 mg) was added to a solution of 2-{4-cyano-4-[5-({5-methyl-1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazole-4-carbonyl}amino)pyridin-2-yl]piperidin-1-yl}-2-methylpropanoic acid ethyl ester (320 mg) in tetrahydrofuran (3.7 ml) and stirred at room temperature for 1.5 hours. Then, lithium borohydride (25 mg) was added and stirred at 80° C. for 2 hours. To the reaction solution, were added methanol (1.5 ml) and sodium borohydride (85 mg), and stirred at room temperature for an hour. A saturated aqueous solution of ammonium chloride was added to the reaction solution, extracted with dichloromethane, and the organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was purified with silica gel chromatography (chloroform/methanol) to give the titled compound (35 mg) as a white solid.

Provenance & Evidence