Carbon Dioxide → HCID 68512093, compound

Participants

Reaction Steps

To a stirred solution of 1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (0.341 g, 1.53 mmol; prepared from cyclopropane-1,1-dicarboxylic acid and 4-fluoroaniline using the methods of WO 2005/030140 and by Shih and Rankin, Synth. Comm., 1996, 26(4), 833-836), catalytic DMF (5 microliters), and THF (5 mL), was added oxalyl dichloride (0.194 g, 1.53 mmol) at room temperature under N2. The reaction was stirred for 30 minutes at room temperature as CO2 evolved. Then 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.500 g, 1.02 mmol) was added as a solution in THF (2 mL). After stirring for 1 hour at room temperature, the reaction mixture was diluted with 5% MeOH/DCM (100 mL), saturated aqueous NaHCO3 (25 mL), and water (125 mL). The cloudy phases were filtered through celite. The phases were separated, and the organic phase washed with 1N NaOH (50 mL) and then brine (50 mL). The organic phases were dried (Na2SO4), filtered, and concentrated in vacuo. The resulting residue was triturated with diethyl ether (50 mL) and filtered. The solid was discarded. The filtrate was concentrated, and the residue purified by preparative TLC, eluting with 10% MeOH/DCM. The product was used in the next step without further purification. Yield: 25 mg, 2.5%. LRMS (APCI+): m/z 696 (M+1) detected.

Provenance & Evidence