Water → N1-(cyanomethyl)-N2-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1-methyl-1H-pyrazol-3-yl)leucinamide

Participants

Reaction Conditions

Reaction Steps

To N2-(4-bromo-1-methyl-1H-pyrazol-3-yl)-N1-(cyanomethyl)leucinamide (250 mg, 0.762 mmol), and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (350 mg, 1.14 mmol, prepared as described in Example 1) in DMF (8 mL) under dry nitrogen was added aqueous sodium carbonate (2.0 M, 0.9 mL, 1.7 mmol) followed by the catalyst PdCl2(dppf) (20 mg, 0.022 mmol). The reaction was heated to 90° C. for 0.5 hours and an additional aliquot of PdCl2(dppf) (20 mg, 0.022 mmol) was added and the reaction mixture heated for 1½ hour during which time an additional aliquot of PdCl2(dppf) (20 mg, 0.022 mmol) was added. Water was added and the product extracted with ether (2×), dried over Na2SO4, concentrated in vacuo and purified by flash chromatography over silica gel (EtOAc/Hex, 6/4 then 8/2) to afford N1-(cyanomethyl)-N2-(4-{4-[4-(tert-butoxycarbonyl)piperazin-1-yl]phenyl}-1-methyl-1H-pyrazol-3-yl)leucinamide.

Provenance & Evidence