Hydrochloric Acid → HCID 178513766, compound

Temperature

55 °C

To a solution containing a mixture of 3-(pyridin-4-ylamino)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-4-carbonitrile and 5-(pyridin-4-ylamino)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole-4-carbonitrile (150 mg, 0.5 mmol) in DMSO (1.2 mL) and EtOH (1.2 mL) was added 5M aqueous NaOH (0.7 mL, 3.3 mmol). The mixture was heated to 55° C., followed by the dropwise addition of 30% H2O2 (0.7 mL, 7.1 mmol). After 10 minutes, additional 30% H2O2 (0.30 mL, 3.4 mmol) was added dropwise. The mixture was maintained for 30 minutes before it was allowed to cool to ambient temperature. To the crude reaction mixture was added MeOH (1 mL) and 6N aqueous HCl (2 mL). The resulting mixture was heated at 55° C. for 1.5 hours. Additional 6N aqueous HCl (1 mL) was added and the mixture continued stirring for another 1 hour. The mixture was cooled to ambient temperature and carefully neutralized with 5N aqueous NaOH until pH 6-7. The mixture was then concentrated in vacuo to remove most of the solvent. To the slurry-like residue was added MeOH (20 mL), and the resulting mixture was sonicated for 5 minutes. The mixture was filtered to remove insoluble precipitate and the filtrate was concentrated in vacuo to afford crude residue containing the title compound, Intermediate #34-1, which was used without further purification.

1. additionTo a solution containing
2. temperatureThe mixture was maintained for 30 minutes before it
3. temperatureto cool to ambient temperature
4. customTo the crude reaction mixture
5. temperatureThe resulting mixture was heated at 55° C. for 1.5 hours
6. temperatureThe mixture was cooled to ambient temperature
7. concentrationThe mixture was then concentrated in vacuo
8. customto remove most of the solvent
9. additionTo the slurry-like residue was added MeOH (20 mL)
10. customthe resulting mixture was sonicated for 5 minutes
11. filtrationThe mixture was filtered
12. customto remove insoluble precipitate
13. concentrationthe filtrate was concentrated in vacuo
14. customto afford crude residue

ORD record

ord-960bac59cbb14fd6b878bf1db180ee08

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328099B2