Thionyl Chloride → 2-Chloronicotinoyl chloride

A mixture of 1.512 g (9.5 mmol) of 2-chloronicotinic acid, 15 ml of thionyl chloride and two droplets of DMF was heated under reflux for 2 hours. The reaction mixture was allowed to cool, and then concentrated under reduced pressure. The resulting residue was then dissolved in 10 ml of acetone to obtain an acetone solution of 2-chloronicotinoyl chloride. 804 mg of ammonium thiocyanate was then dissolved in 15 ml of acetone. To the solution thus obtained was then added dropwise the acetone solution of 2-chloronicotinoyl chloride with stirring in 5 minutes. The reaction mixture was then stirred over a 40° C. oil bath for 5 minutes. The resulting insoluble matters were then removed by filtration to obtain an acetone solution of 2-chloronicotinoyl isothiocyanate. To the solution thus obtained was then added dropwise a mixture of 1.685 g of 5-(N-ethylamino)-1-methyl-1H-benzimidazole and 10 ml of acetone with stirring in 5 minutes. The reaction mixture was further stirred for 6 hours, and then poured into about 1,000 ml of ice-water. The resulting crystal was collected by filtration, washed with water, and then dried under reduced pressure. The compound thus obtained was suspended in 30 ml of toluene, and then heated under reflux for 2 hours. After allowed to cool, the reaction mixture was collected by filtration, and then recrystallized from a mixture of ethanol and ether to obtain 1.171 g of 2-[N-ethyl-N-(1H-1-methylbenzimidazol-5-yl)amino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one hydrochloride.

1. temperaturewas heated
2. temperatureunder reflux for 2 hours
3. temperatureto cool
4. concentrationconcentrated under reduced pressure
5. dissolutionThe resulting residue was then dissolved in 10 ml of acetone

ORD record

ord-144ccbaeab29450a9b97adf615a037db

Source dataset

uspto-grants-2000_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06133258