Hydrochloric Acid → 6-Nitro-1H-indazole-3-carboxylic acid

Temperature

100 °C

A 5 mL microwave reaction vessel was charged with 3-iodo-6-nitroindazole (1 mmol), copper (I) cyanide (2 mmol) and N,N-dimethylformamide (3 mL). The vessel was sealed and subjected to microwave irradiation at 185° C. for 600 sec. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 mL) and the mixture was filtered through Celite. The organic layer was collected, washed with brine, dried (magnesium sulfate), and concentrated to give 122 mg of a 10/1 mixture of 3-cyano-6-nitroindazole and 6-nitroindazole as a yellow solid. The 10/1 mixture of 3-cyano-6-nitroindazole and 6-nitroindazole was dissolved in 10 N sodium hydroxide and the bright orange solution was heated at 100° C. for 1 h. The mixture was allowed to cool to room temperature and carefully acidified (pH=1) with 3 N hydrochloric acid. The solid was isolated and triturated with EtOAc to provide 51 mg of 6-nitroindazole-3-carboxylic acid as a brown solid. The acid was coupled with the bicyclobase according to procedure A. 3-Iodo-6-nitroindazole was prepared from 6-nitroindazole using the method of Collot, C., et al., Tetrahedron, 55, 6917 (1999).

1. customThe vessel was sealed
2. customirradiation at 185° C. for 600 sec
3. customThe reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 mL)
4. filtrationthe mixture was filtered through Celite
5. customThe organic layer was collected
6. washwashed with brine
7. dry with materialdried (magnesium sulfate)
8. concentrationconcentrated
9. customto give
10. temperatureto cool to room temperature
11. customThe solid was isolated
12. customtriturated with EtOAc

ORD record

ord-a30a2bbde1d74ff79f4a17c8a73d631f

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07488737B2