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

関与物質

反応条件

反応手順

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-dimethoxy-phenyl)-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 one 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, and the reaction mixture was cooled to room temperature. The solid that precipitated 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]pyrimidine-7-one. Proton NMR (DMSO) is consistent with the structure: 1H NMR (DMSO): δ 8.86 (s, 1H), 8.10 (s, 1H), 6.83 (d, 2H), 6.51 (s, 1H), 4.36 (q, 2H), 3.75 (s, 1H), 2.58 (s, 3H), 1.22 (t, 3H). The combined mother liquor and washes were allowed to stand at room temperature for seven days. At this time a second crop of precipitate 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.

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