2-Pyrazinecarboxylic acid → Pyrazinamide

Temperature

23 °C

Diethylaniline (0.33 μL, 2.1 μmol, 1.1 equiv) was added in one portion to a stirred solution of the amine (1.0 mg, 1.9 μmol, 1 equiv) in THF (0.2 mL) at 0° C. under an argon atmosphere and the solution was stirred for 5 min. 2-Pyrazinecarboxylic acid (0.31 mg, 2.5 μmol, 1.3 equiv), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.48 mg, 2.5 μmol, 1.3 equiv) and 1-hydroxybenzotriazole (0.31 mg, 2.3 μmol, 1.2 equiv) were then added separately, each in one portion, to the above solution at 0° C. The reaction mixture was warmed to 23° C. over 17 h 40 min, then was quenched with saturated aqueous ammonium chloride solution (3 mL). The mixture was diluted with ethyl acetate (10 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (10 mL) and the combined organic layer was dried over sodium sulfate. Concentration in vacuo left a white solid, which was purified by flash column chromatography (80% ethyl acetate-hexanes) to give the pyrazine-2-carboxylic acid amide derivative (1.1 mg, 92%) as a white solid.

1. customat 0° C
2. customwas quenched with saturated aqueous ammonium chloride solution (3 mL)
3. additionThe mixture was diluted with ethyl acetate (10 mL)
4. customthe layers were separated
5. extractionThe aqueous layer was extracted with ethyl acetate (10 mL)
6. dry with materialthe combined organic layer was dried over sodium sulfate
7. concentrationConcentration in vacuo
8. waitleft a white solid, which
9. customwas purified by flash column chromatography (80% ethyl acetate-hexanes)

ORD record

ord-50c74831cfcb4e1e8ad6295c27f1b427

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06809099B2