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

Participants

Reaction Steps

The compound was synthesized following the approach outlined in Procedure 2G (Example 123), substituting 3-fluoro-2-nitroaniline in step (d), omitting step (e), and modifying step (g) to the following procedure: To a solution of 1-(6-((2-amino-3-methylphenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)urea (31 mg, 0.051 mmol), diisopropyl ethylamine (13.1 g, 0.103 mmol), and acrylic acid (39.9 g, 0.055 mmol) in DCM (1 ml, 15.54 mmol) was added a solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (48.1 g, 0.076 mmol, 50% solution EtOAc) at 0° C., and the resulting mixture was stirred at room temperature for 2 h. The mixture was concentrated and the residue was purified by silica gel column to obtain the SEM protected title compound (24 mg, yield: 71% in three steps). Following the final step (g), the title compound was isolated (12 mg, yield: 62%). 1H-NMR (400 MHz, CDCl3) δ 3.40 (s, 3H) 3.93 (m, 6H) 5.91 (d, 1H) 6.20 (s, 1H) 6.30-6.45 (m, 1H) 6.50-6.58 (m, 2H) 7.01 (t, 1H) 7.28-7.35 (m, 1H) 7.42-7.63 (m, 2H) 8.41 (s, 1H) 12.43 (br. s., 1H); ESI-MS: 535 [M+H]+.

Provenance & Evidence