Acetic Acid → 7-bromo-5-nitro-1H-indazole

Reaction equation

[N:1]([O-])=O.[Na+].[Br:5][C:6]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[CH:10]=[C:9]([CH3:16])[C:7]=1[NH2:8].CC(O)=O>O>[Br:5][C:6]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[CH:10]=[C:9]2[C:7]=1[NH:8][N:1]=[CH:16]2

Participants

Procedure

NaNO2 (65.00 g, 942.0 mmol) in H2O (140 mL) was added via addition funnel to a 5 L 3-neck round bottom flask, equipped with a mechanical stirrer and a thermometer, containing a mixture of crude 2-bromo-6-methyl-4-nitroaniline (145.0 g, 627.6 mmol) and glacial HOAc (2.5 L). During the addition, the reaction mixture was cooled with an ice bath to to maintain the internal reaction temperature below 25° C. About 1 hour after the addition was complete, additional NaNO2 (21.65 g, 313.8 mmol) in H2O (50 mL) was added to the reaction mixture relatively rapidly (<5 min) with no evidence of an exotherm. After an additional 1 hour, the reaction mixture was concentrated under reduced pressure. The resulting solid was triturated with MeOH/H2O (1:1, 1 L) then filtered, washed with additional MeOH/H2O (1:1, 500 mL), and dried in a vacuum oven at about 50-60° C. for about 16 hours to give 7-bromo-5-nitro-1H-indazole (109.4 g, 72%, 90% pure by HPLC); 1H NMR (DMSO-d6, 400 MHz) 14.28 (br s, 1H), 8.87 (d, J=1.9 Hz, 1H), 8.57 (s, 1H), 8.40 (d, J=1.9 Hz, 1H); LC/MS (Table 1, Method e) Rt 1.75 min; m/z (ESI−) 241.7.