Acetic Acid → HCID 178434617, compound

Temperature

90 °C

To a suspension of tert-butyl cis-4-carbamoylcyclohexylcarbamate (0.24 g, 0.990 mmol) in toluene (0.8 mL) was added N,N-dimethylacetamide dimethyl acetal (2.90 mL, 19.81 mmol), and the resulting mixture was refluxed for 16 hours with a Dean-Stark trap attached. The mixture was allowed to cool, was diluted with EtOAc (30 mL), and was washed with water (2-10 mL) and then brine (10 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a brown oil. A premixed solution of hydrazine (0.078 mL, 2.476 mmol) and AcOH (8.22 mL, 144 mmol) was added to the residual oil, and the resulting mixture was heated at 90° C. for 3 hours. The mixture was allowed to cool and poured into water (30 mL). The mixture was extracted with EtOAc (50 mL), and the organic layer was separated and washed sequentially with water (10 mL), aqueous NaHCO3 (10 mL), and brine (10 mL), then dried over Na2SO4, filtered and concentrated under reduced pressure to give a tan solid. The solid was suspended in HCl (4M in dioxanes) (12.38 mL, 49.5 mmol) and stirred at RT for 16 hours. The mixture was concentrated to dryness under reduced pressure to afford cis-4-(3-methyl-1H-1,2,4-triazol-5-yl)cyclohexanamine hydrochloride as a tan solid (0.15 g, 0.692 mmol, 69.9% yield). MS m/z=181.2 [M+H]. Calc'd for C9H16N5: 180.1.

1. temperaturethe resulting mixture was refluxed for 16 hours with a Dean-Stark trap
2. temperatureto cool
3. washwas washed with water (2-10 mL)
4. dry with materialThe organic layer was dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give a brown oil
8. temperatureto cool
9. extractionThe mixture was extracted with EtOAc (50 mL)
10. customthe organic layer was separated
11. washwashed sequentially with water (10 mL), aqueous NaHCO3 (10 mL), and brine (10 mL)
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customto give a tan solid
16. concentrationThe mixture was concentrated to dryness under reduced pressure

ORD record

ord-0c54c3ffc0fa4f5e8831c7cd0d256e7f

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115127B2