Benzophenone imine → 1-Methyl-1H-indazol-3-amine

A mixture of palladium (II) acetate (82 mg, 2% mol) and xantphos (287 mg, 3% mol) in toluene (10 mL) was stirred for 5 minutes at ambient temperature. To the solution was added a solution of Example 2C (3.68 g, 17.4 mmol) and benzophenone imine (3.0 g, 17.4 mmol) in toluene (30 mL). The mixture was evacuated and purged with nitrogen two times, then stirred at ambient temperature for 15 minutes. sodium tert-butoxide (1.9 g, 1.4 eq) was added and the mixture was evacuated and purged with nitrogen. The mixture was heated to between 80-85° C. for 2 hours, cooled to ambient temperature and diluted with water (30 mL). The aqueous layer was separated and extracted with additional toluene (20 mL). The combined organic layers were stirred with 6 N HCl (10 mL) for 1 hour and 40 mL of water added to dissolve the solids. The toluene layer was discarded and aqueous layer filtered to remove insoluble material. The aqueous layer was adjusted to the pH of 14 with 50% NaOH and filtered to provide the title compound. The solid was dissolved in acetonitrile (25 mL) followed by the slow addition of 12 M HCl to adjust the pH to 1. The precipitate was filtered off, washed with water and dried to provide the hydrochloride salt of the title compound. 1H NMR (DMSO) δ 8.03 (d, 1H), 7.02 (dd, 1H), 6.64 (dt, 1H), 6.14 (dd, 1H), 5.73 (brs, 2H), 3.90 (s, 3H).

1. customThe mixture was evacuated
2. custompurged with nitrogen two times
3. stirringstirred at ambient temperature for 15 minutes
4. customthe mixture was evacuated
5. custompurged with nitrogen
6. temperatureThe mixture was heated to between 80-85° C. for 2 hours
7. temperaturecooled to ambient temperature
8. additiondiluted with water (30 mL)
9. customThe aqueous layer was separated
10. extractionextracted with additional toluene (20 mL)
11. stirringThe combined organic layers were stirred with 6 N HCl (10 mL) for 1 hour
12. addition40 mL of water added
13. dissolutionto dissolve the solids
14. filtrationaqueous layer filtered
15. customto remove insoluble material
16. filtrationfiltered

ORD-Eintrag

ord-1733c361684f41a98eabe739e3323f73

Quelldatensatz

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07767705B2