Iodine → 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one

Participants

Reaction Conditions

Reaction Steps

A 5-L round bottomed flask was charged with 516 g (2.62 mol) of 4-ethylamino-2-methylsulfanyl-pyrimidine-5-carboxaldehyde, 587 g (2.62 mol) of (3,5-dimethoxyphenyl)-acetic acid ethyl ester and 391 mL (2.62 mol) of 1,8-diazabicyclo[5.4.0]undec-7-ene. The mixture was heated at 80° C. for 1 hour. Thin layer chromatography (TLC) (silica, 6:4/heptane:ethyl acetate, developed in an iodine chamber) showed all the 4-ethylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde was consumed. Ethyl alcohol (absolute, 2.75 L) was added to the reaction vessel, which was allowed to cool to room temperature. The solid was collected by filtration, washed once with ethyl alcohol, and dried in a vacuum oven at 45° C. for 12 hours to provide 530 g (57% yield) of 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidin-7-one. Proton NMR (s,1H), 6.83 (d, 2H), 6.51 (s, 1H), 4.36 (q, 2H), 3.75 (s, 1H), 2.58 (s, 3H), (t, 3H). The combined mother liquor and washes were allowed to stand at room temperature for 7 days. At this time a second crop was collected, washed once with ethyl alcohol, and dried in a vacuum oven at 45° C. for 12 hours to provide 79 g (8.5% yield) of 2-(methylsulfanyl)-6-(3,5-dimethoxyphenyl)-8-ethyl-8H-pyrido[2,3-d]pyrimidine-7-one. Proton NMR (DMSO) is consistent with the structure.

Provenance & Evidence