1-Methylpiperazine → 3-Methyl-4-(4-methyl-piperazin-1-yl)isoxazolo[5,4-b]pyridine-5-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl 4-chloro-3-methylisoxazolo[5,4-b]pyridin-5-carboxylate (1.02 g) and 1-methylpiperazine (1.12 ml) in tetrahydrofuran (10 ml) was stirred at room temperature for 1 hr and then concentrated under reduced pressure. The residue was treated with water, the precipitated solid was filtered, washed with water, and dried under high vacuum. This solid was suspended in ethanol (11 ml), added 5N NaOH (11 ml), and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was treated with 5N HCl and purified by ODS column (VARIAN MEGABOND ELUT C18) to give 3-methyl-4-(4-methyl-piperazin-1-yl)isoxazolo[5,4-b]pyridine-5-carboxylic acid as an amorphous solid. A portion of this amorphous solid (417 mg) was dissolved in thionyl chloride (40 ml) and heated at 50° C. for 3.5 hrs. The mixture was concentrated under reduced pressure, the residue was dissolved in THF (20 ml), and reacted with ammonia gas at room temperature for 3 hrs. The reaction mixture was concentrated under reduced pressure, the residue was treated with water, the resulting solid was filtered, washed with water, and dried under high vacuum to give the 3-methyl-4-(4-methylpiperazin-1-yl)-isoxazolo[5,4-b]pyridine-5-carboxylic acid amide.

Provenance & Evidence