5-Amino-2-chloropyridine → Ethyl 3-(6-chloropyridin-3-ylamino)-2-(methylsulfonyl)acrylate

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 3-ethoxy-2-(methylsulfonyl)acrylate (7.0 g, 32 mmol) and 2-chloro-5-aminopyridine (4.1 g, 32 mmol) in chlorobenzene (16 mL) was stirred with heat at 135° C. for 3 h in a round bottomed flask that was equipped with a short path distillation apparatus to collect the ethanol generated during the reaction. The reaction was cooled, concentrated and the residue was purified by chromatography (silica, methylene chloride/ethyl acetate) to afford the desired product (8.2 g, 84%) as a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 10.61 (d, 13.4 Hz, 1H), 8.34 (d, J=13.4 Hz, 1H), 8.27 (d, J=2.9 Hz, 1H), 7.50 (dd, J=8.6, 3.0 Hz, 1H), 7.37 (d, J=8.6 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 3.18 (s, 3H), 1.42 (t, J=7.2 Hz, 3H); ESI MS m/z 305 [M+H]+.

Provenance & Evidence