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

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Reaction Conditions

Reaction Steps

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)+.

Provenance & Evidence