Thionyl Chloride → 2-Chloronicotinoyl chloride

A mixture of 2.437 g (15.47 mmol) of 2-chloronicotinic acid, 15 ml of thionyl chloride and two droplets of DMF was heated under reflux for two hours. The reaction solution was allowed to cool, and then concentrated under reduced pressure to obtain 2-chloronicotinoyl chloride. The compound thus obtained was then dissolved in 10 ml of acetone. The solution thus obtained was then added dropwise to a solution of 1.30 g of ammonium thiocyanate in 15 ml of acetone with stirring in 5 minutes. After the termination of dropwise addition, the reaction mixture was heated to a temperature of 40° C. with stirring for 6 minutes. The resulting insoluble matters were then removed by filtration to obtain a solution of 2-chloronicotinoyl isothiocyanate. To the solution was then added dropwise a solution of 1.98 g of 1-methyl-4-(methylamino)piperidine in 10 ml of THF with stirring in 5 minutes. The reaction mixture was stirred at room temperature for 17 hours, and then concentrated under reduced pressure. The resulting residue was then purified through silica gel column chromatography (eluant: 20:1:0.1 to 10:1:0.1 mixture of CHCl3, methanol and 30% aqueous ammonia) to obtain 3.98 g of 1-(1-methyl-4-piperidyl)-3-(2-chloronicotinoyl)-1-methylthiourea.

1. temperaturewas heated
2. temperatureunder reflux for two hours
3. temperatureto cool
4. concentrationconcentrated under reduced pressure

ORD record

ord-5bfb064680f743ec99bfa478e982003f

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06133258