Hydrochloric Acid → 7-Chloro-1H-indazole-5-carbonitrile

To a mixture of 4-amino-5-methyl-benzonitrile (3.0 g, 18.0 mmol) in chloroform (50 mL) was added acetic anhydride (3.92 mL, 41.4 mmol). The mixture was heated at reflux for 5 hours and then cooled to room temperature. To the mixture was added potassium acetate (530 mg, 5.4 mmol) and isoamyl nitrite (5.28 mL, 39.6 mmol). The reaction was heated at reflux for 16 hours. The reaction mixture was coded to room temperature, extracted with saturated aqueous sodium bicarbonate, the organics were dried over sodium sulfate, and concentrated in vacuo to afford a brown oil. The oil was dissolved in methanol (25 mL) and concentrated hydrochloric acid (25 mL) was added. The reaction was stirred at room temperature for 22 hours and the methanol was concentrated in vacuo. The remaining aqueous layer was adjusted to a pH of 7 and the resultant precipitate was filtered to afford a brown solid which was purified by flash chromatography using 50% dichloromethane in heptane as eluent to afford 7-chloro-1H-indazole-5-carbonitrile as a solid (585 mg, 18%): −ESI MS (M−1) 176.0; 1H NMR (400 MHz, CDC3) 5 ppm 8.29 (br. s., 2H), 8.08 (s, 1H), 7.61 (s, 1H).

1. temperatureThe mixture was heated
2. temperatureat reflux for 5 hours
3. temperatureThe reaction was heated
4. temperatureat reflux for 16 hours
5. customwas coded to room temperature
6. extractionextracted with saturated aqueous sodium bicarbonate
7. dry with materialthe organics were dried over sodium sulfate
8. concentrationconcentrated in vacuo
9. customto afford a brown oil
10. concentrationthe methanol was concentrated in vacuo
11. filtrationthe resultant precipitate was filtered
12. customto afford a brown solid which
13. customwas purified by flash chromatography

ORD record

ord-cf9bace28d374210b86409414f87c9cd

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802690B2