Sodium Carbonate → 4-(2-Methylpyridin-3-yl)-6-tert-butylpyrimidine

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Reaction Steps

Next, 2.0 g of 4-tert-butyl-6-chloropyrimidine obtained in Step 2, 3.0 g of 2-methylpyridine-3-boronic acid pinacol ester, 17 mL of a 1M aqueous solution of potassium acetate, 17 mL of a 1M aqueous solution of sodium carbonate, and 40 mL of acetonitrile were put in a 100-mL round-bottom flask, and the air in the flask was replaced with argon. To this mixture, 0.78 g of tetrakis(triphenylphosphine)palladium(0) was added, and the mixture was irradiated with microwaves under conditions of 100° C. and 100 W for 1 hour to cause a reaction. This reaction mixture was subjected to extraction with ethyl acetate, and washing with a saturated aqueous solution of sodium chloride was performed. Anhydrous magnesium sulfate was added to the obtained solution of the extract for drying, and the resulting mixture was gravity-filtered to give a filtrate. The resulting filtrate was dissolved in a mixed solvent of ethyl acetate and hexane, and the mixture was filtered through Celite, alumina, and Celite. The resulting filtrate was purified by silica gel column chromatography. As a developing solvent, a mixed solvent of hexane and ethyl acetate in a ratio of 3:2 (v/v) was used. The obtained fraction was condensed to give an oily substance. This oily substance was dissolved in a mixed solvent of hexane and ethyl acetate, and the solution was filtered through a filter aid in which Celite, alumina, and Celite were stacked in this order. The resulting filtrate was condensed to give HtBumpypm (light-yellow oily substance, yield of 92%). Synthesis Scheme (b-3) of Step 3 is shown below.

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