2-Amino-3-methylpyridine → 4-(8-Methylimidazo[1,2-a]pyridin-3-yl)-2-(methylthio)pyrimidine-5-carbonitrile

Participants

Reaction Steps

10 g of 4-[(Z)-2-ethoxyvinyl]-2-(methylthio)-5-pyrimidinecarbonitrile (synthesized according to the method disclosed in International Publication WO2006/025567, pages 90-91) was dissolved in a mixed solvent of 150 mL of 1,4-dioxane and 30 mL of water and then 8.04 g of N-bromosuccinimide was added thereto under an ice-cold condition, and the mixture was stirred for 1.5 hours at room temperature. To the reaction solution, 4.89 g of 2-amino-3-picoline was added, and the mixture was further stirred for 2.5 hours. 200 mL of water was added to the reaction solution to extract with 2 L of a mixed solvent of chloroform and methanol (mixing ratio: 9/1). The organic layer was washed with water, and dried over anhydrous magnesium sulfate. Thereafter, the insolubles were filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in a small amount of chloroform and solidified with hexane to obtain 4.02 g of 4-(8-methylimidazo[1,2-a]pyridin-3-yl)-2-(methylthio)pyrimidine-5-carbonitrile [1-6] (hereinafter, referred to as the compound [1-6]) as a light brown solid.

Provenance & Evidence