Benzyl Bromide → Benzyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinylpyrimidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinylpyrimidine-4-carboxylic acid (prepared by the methods described in U.S. Pat. No. 7,786,044 B2; 0.150 g, 0.463 mmol), (bromomethyl)benzene (0.103 g, 0.602 mmol), and lithium carbonate (Li2CO3; 0.044 g, 0.602 mmol) were combined in DMF (1.5 mL) and heated at 60° C. overnight. The cooled reaction mixture was concentrated and then partitioned between EtOAc and water. The organic phase was dried, concentrated and purified by column chromatography (eluting with an EtOAc/hexanes gradient) to yield benzyl 6-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinylpyrimidine-4-carboxylate as a white solid (0.154 g, 80%): mp 119-121° C.; 1H NMR (400 MHz, CDCl3) δ 7.67 (dd, J=8.5, 7.5 Hz, 1H), 7.49-7.42 (m, 2H), 7.42-7.32 (m, 3H), 7.21 (dd, J=8.6, 1.7 Hz, 1H), 6.70 (dd, J=17.8, 11.6 Hz, 1H), 5.60 (dd, J=7.7, 1.0 Hz, 1H), 5.57 (s, 1H), 5.39 (s, 2H), 5.35 (s, 2H), 4.00 (d, J=0.8 Hz, 3H); ESIMS m/z 414 ([M+H]+).

Provenance & Evidence