Methacryloyl chloride → HCID 89629892, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (3-methylphenyl)boronic acid (26.4 mg, 0.194 mmol), tert-butyl 5-bromo-4-{3-[(tert-butoxycarbonyl)amino]phenyl}-7H-pyrrolo[2,3-d]pyrimidine-7-carboxylate (50 mg, 0.10 mmol), potassium phosphate (1 M aqueous solution, 511 μL, 0.511 mmol), and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (6.66 mg, 10.2 μmol) in degassed toluene (1.02 mL) was heated to 60° C. for 18 hours. The reaction mixture was filtered through Celite and concentrated under reduced pressure. The crude residue was dissolved in 0.5 mL of DCM:TFA:Water (50:48:2) and stirred at room temperature for 2 hours before being concentrated under reduced pressure. To this deprotected intermediate was added DMF (0.50 mL), TEA (57 μl, 0.41 mmol), 3-(diethoxyphosphorylloxy)-1,2,3-benzotriazin-4-(3H)-one (61.1 mg, 0.204 mmol) and 2-methylprop-2-enoyl chloride (17.6 mg, 0.204 mmol). The reaction mixture was stirred at room temperature for 20 hours, filtered, and purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier to afford 2-methyl-N-{3-[5-(3-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]phenyl}prop-2-enamide. LRMS (ESI) calc'd for C23H21N4O [M+H]+: 369, found 369. 1H NMR (600 MHz, DMSO-D6) δ 12.71 (br s, 1H); 9.60 (s, 1H); 8.91 (s, 1H); 7.81 (br s, 1H); 7.74 (s, 1H); 7.65 (d, 1H, J=6.0 Hz), 7.07 (dd, 1H, J=6.5, 6.5 Hz); 6.94 (d, 2H, J=6.0 Hz); 6.88 (d, 1H, J=6.5 Hz); 6.80 (d, 1H, J=5.5 Hz); 6.62 (s, 1H); 5.67 (s, 1H); 5.46 (s, 1H); 1.99 (s, 3H); 1.88 (s, 3H).

Provenance & Evidence