Sodium Hydroxide → 2-Amino-N-1H-imidazol-2-yl-3-nitrobenzamide

Temperature

75 °C

5.0 g (27.4 mmol) of 2-amino-3-nitro-benzoic acid, 12.48 g (32.9 mmol) of HBTU were suspended in 20 mL of DMF. To this suspension, 10 mL of DIEA was added, and the resulting mixture was stirred for 10 minutes to form a paste. To this paste, 10 mL of DMF was added followed by 9 g (68.2 mmol) of 2-amino imidazole sulfate. The resulting mixture was heated at 75° C. for 3.0 h. The reaction mixture was cooled to room temperature and 5 mL of 2N NaOH was added followed by 200 mL of brine solution. A solid precipitated from the solution and was collected by filtration, washed with water (300 ml), ethyl acetate (100 ml), and dried under vacuum to provide 5.3 g (75%) of 2-amino-N-(1H-imidazol-2-yl)-3-nitro-benzamide as a yellow solid. The product was hydrogenated according to the general procedure C to give 2,3-diamino-N-(1H-imidazol-2-yl)-benzamide (4.5 g) 4.5 g (21.2 mmol) of the above solid was dissolved in a mixture of 40 mL of ethanol and 8 mL of H2O. To this stirring solution 3.3 g (31.8 mmol) of BrCN was added and the resulting mixture was refluxed for 1.0 h. The reaction mixture was cooled to room temperature and the solvent was evaporated and adjusted to ˜pH 8.0 with aqueous NH4OH. The resulting solid was filtered. The solid was further washed with water (100 mL), ethyl acetate (50 mL) and dried under vacuum to give 2.5 g (50%) of 2-amino-3H-benzoimidazole-4-carboxylic acid (1H-imidazol-2-yl)-amide. LCMS: 243 (M+1)+.

1. customto form a paste
2. temperatureThe reaction mixture was cooled to room temperature
3. customA solid precipitated from the solution
4. filtrationwas collected by filtration
5. washwashed with water (300 ml), ethyl acetate (100 ml)
6. customdried under vacuum

ORD record

ord-6ea169bd37214facb597e600a7b97cc9

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598353B2