Dichloromethane → (E)-3-chloro-N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)acrylamide

Participants

Reaction Steps

The title compound was synthesized following the approach outlined in Procedure 2A (Example 100), modifying step (i) to the following procedure: To a solution of 1-(6-((2-aminophenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylurea (10 mg, 0.022 mmol), triethylamine (10.9 g, 0.11 mmol), and (E)-3-chloroacrylic acid (2.76 g, 0.026 mmol) in DCM (0.4 ml, 6.22 mmol), cooled to 0° C., was added 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (0.023 ml, 0.039 mmol, 50% solution in EtOAc). The resulting mixture was stirred at room temperature for 4 h and concentrated. The remaining residue was purified by silica gel flash chromatography to obtain the title compound (7.2 mg, yield: 61%). 1H NMR (400 MHz, CDCl3) δ 3.30 (s, 3H) 3.90 (s, 6H) 6.02 (s, 1H) 6.36 (d, J=12.92 Hz, 1H) 6.49 (s, 1H) 7.21-7.33 (m, 2H) 7.36-7.50 (m, 2H) 7.75 (d, J=6.53 Hz, 1H) 7.93 (br. s., 1H) 8.41 (s, 1H) 12.50 (s, 1H); MS (ESI): 551.0 [M+H]+

Provenance & Evidence