Phosphorus oxychloride → 3-(2-Chloroethyl)imidazo[1,5-a]pyrazine

To a solution of N-(2-pyrazinylmethyl)-3-chloropropionamide (4.52 g) in dichloromethane (30 ml) was added phosphorus oxychloride (1.29 g) under ice cooling. The mixture was stirred for 3 days at room temperature. The mixture was concentrated, and the residue was poured into ice water (400 ml), followed by neutralization with sodium carbonate. The reaction mixture was subjected to salting out with sodium chloride, and extracted with ethyl acetate-THF (1:1, 150 ml×3). The organic layers were combined and dried over magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was subjected to flash column chromatography [carrier: silica gel, 100 g, developing solvent: ethyl acetate→ethyl acetate-ethanol (9:1)]. The eluate was concentrated and residual solid was washed with diethylether to give the title compound (3.07 g) as colorless solid product.

1. concentrationThe mixture was concentrated
2. additionthe residue was poured into ice water (400 ml)
3. extractionextracted with ethyl acetate-THF (1:1, 150 ml×3)
4. dry with materialdried over magnesium sulfate
5. distillationThe solvent was distilled off under reduced pressure
6. concentrationThe eluate was concentrated
7. washresidual solid was washed with diethylether

ORD record

ord-b88d7951211d4d7f9dcd0c0bec763463

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06174877B1