Diisopropylethylamine → Ethyl 4-chloro-6-((4-ethoxy-4-oxobutyl)(4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

The mixture of ethyl 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylate (7.9 g, 29.88 mmol) and ethyl 4-((4-methoxybenzyl)amino)butanoate (5 g, 19.92 mmol) in DMF (500 mL) and DIPEA (4.6 g, 35.85 mmol) was heated at 80° C. for 2 h. The reaction mixture was then cooled to room temperature and crushed ice was added. The reaction mixture was extracted with EtOAc (3×100 mL), and the combined EtOAc layer was dried over sodium sulphate, filtered and evaporated under reduced pressure to give a residue which was purified by column chromatography (silica gel, gradient 0-5% EtOAc in hexanes) to afford ethyl 4-chloro-6-((4-ethoxy-4-oxobutyl)(4-methoxybenzyl)amino)-2-(methylthio)pyrimidine-5-carboxylate (5.5 g, 40%). 1H NMR (400 MHz, CDCl3): δ 7.12 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 4.66 (s, 2H), 4.16 (q, J=6.8 Hz, 2H), 4.10 (q, J=7.2 Hz, 2H), 3.79 (s, 3H), 3.42 (t, J=7.6 Hz, 2H), 2.45 (s, 3H), 2.24 (t, J=6.8 Hz, 2H), 1.94 (quintet, J=7.2 Hz, 2H), 1.24 (t, J=7.2 Hz, 3H), 1.22 (t, J=7.2 Hz, 3H). LCMS [M+H]: 482

Provenance & Evidence