Trichloroacetyl isocyanate → Urea, [8-(4-cyano-1-naphthalenyl)-8-azabicyclo[3.2.1]oct-3-yl]-

The amine 165RL21 (40 mg, 0.144 mmol) was dissolved in tetrahydrofuran (1 mL) and cooled to 0° C. Trichloroacetyl isocyanate (0.019 mL) was added and the solution was left to warm to rt and stirring was continued for 30 minutes. The mixture was concentrated and the residue was dissolved in methanol (1 mL). 2 M NaOH (1 mL) was added, and the mixture was heated to 70° C. for 1 hour. Then, water (20 mL) was added and methanol was removed by evaporation in vacuo. The aqueous phase was extracted with dichloromethane (2×20 mL), and the combined organic phases were dried over sodium sulfate, filtered and evaporated. The residue was purified by preparative TLC (0-5% methanol in dichloromethane) to give the title compound (24 mg, 52% yield) as a white solid.

1. waitthe solution was left
2. temperatureto warm to rt
3. concentrationThe mixture was concentrated
4. dissolutionthe residue was dissolved in methanol (1 mL)
5. addition2 M NaOH (1 mL) was added
6. temperaturethe mixture was heated to 70° C. for 1 hour
7. additionThen, water (20 mL) was added
8. custommethanol was removed by evaporation in vacuo
9. extractionThe aqueous phase was extracted with dichloromethane (2×20 mL)
10. dry with materialthe combined organic phases were dried over sodium sulfate
11. filtrationfiltered
12. customevaporated
13. customThe residue was purified by preparative TLC (0-5% methanol in dichloromethane)

ORD record

ord-96125bc080a845e78418d8fdb48c03e1

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07268232B2