Hydrazine hydrate (1:1) → 3-Tert-butyl-1-(4,4,4-trifluorobutyl)-1h-pyrazol-5-amine

Temperature

85 °C

To a solution of Example 135A (5 g, 17.7 mmol) in EtOH (50 mL) was added hydrazine hydrate (1.1 mL, 23.0 mmol). The mixture was warmed to reflux (85° C.) and was allowed to stir for 20 hours. The mixture was cooled to ambient temperature then 4,4-dimethyl-3-oxopentanenitrile (2.9 g, 23.0 mmol) was added and the mixture was again warmed to reflux (85° C.) and stirred for 6 hours. After cooling to ambient temperature, the mixture was concentrated under reduced pressure and the residue was dissolved in CH2Cl2 (100 mL) and saturated aqueous NaHCO3 (50 mL) was added slowly. The layers were separated and the aqueous phase was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes in EtOAc to 100% EtOAc to 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (2.0 g, 8.1 mmol, 46% yield). MS (ESI+) m/z 250 (M+H)+.

1. temperatureThe mixture was warmed
2. temperatureThe mixture was cooled to ambient temperature
3. temperaturethe mixture was again warmed
4. temperatureto reflux (85° C.)
5. stirringstirred for 6 hours
6. temperatureAfter cooling to ambient temperature
7. concentrationthe mixture was concentrated under reduced pressure
8. dissolutionthe residue was dissolved in CH2Cl2 (100 mL)
9. additionsaturated aqueous NaHCO3 (50 mL) was added slowly
10. customThe layers were separated
11. extractionthe aqueous phase was extracted with CH2Cl2 (3×10 mL)
12. dry with materialThe combined organic extracts were dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customPurification by column chromatography (SiO2, 50% hexanes in EtOAc to 100% EtOAc to 9:1:0.1 EtOAc:MeOH:Et3N)

ORD record

ord-fff998e4114542d9a2c6b37ecd58c50f

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859596B2