Water → 2-Chloro-5-[(4-methylpiperazin-1-yl)carbonyl]pyrazine

Commercially available 5-hydroxypyrazine-2-carboxylic acid (5.00 g, 39.0 mmol) was dissolved in thionyl chloride (64 mL), and a few drops of N,N-dimethylformamide were added, followed by heating to reflux for 5 hours under nitrogen atmosphere. The solvent was distilled off under reduced pressure, and the resulting residue was diluted with methylene chloride (50 mL). While being cooled in an ice bath, diisopropylethylamine (18.7 mL, 107 mmol) and 1-methylpiperazine (4.37 mL, 39.2 mmol) were added, and stirring was carried out at room temperature for 3 days under nitrogen atmosphere. To the reaction solution, water (100 mL) was added, and extraction was carried out with methylene chloride (100 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: methanol/methylene chloride=3%-5%) to afford the desired compound (5.32 g, yield 62%) as a brown solid.

1. temperatureby heating
2. temperatureto reflux for 5 hours under nitrogen atmosphere
3. distillationThe solvent was distilled off under reduced pressure
4. additionthe resulting residue was diluted with methylene chloride (50 mL)
5. temperatureWhile being cooled in an ice bath
6. extractionextraction
7. washThe organic layer was washed with saturated brine
8. dry with materialsubsequently dried over anhydrous magnesium sulfate
9. distillationThe solvent was distilled off under reduced pressure
10. customthe resulting residue was purified
11. washsilica gel column chromatography (elution solvent: methanol/methylene chloride=3%-5%)

ORD record

ord-db57d6fe268945dbbf9b3ad051cfd4a1

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08017610B2