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

HRID 1678238Notes

Reaction equation

HRID 1678238 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

5

Reactant 3

HCID 176Acetic AcidHCID 2930732-bromo-6-methyl-4-nitroanilineHCID 23668193Sodium Nitrite2×

Product 1

HCID 14819687-bromo-5-nitro-1H-indazoleYield 72%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

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.

Workup

  1. customequipped with a mechanical stirrer
  2. additiona thermometer, containing
  3. additionDuring the addition
  4. temperaturethe reaction mixture was cooled with an ice bath
  5. temperatureto to maintain the internal reaction temperature below 25° C
  6. additionAbout 1 hour after the addition
  7. concentrationthe reaction mixture was concentrated under reduced pressure
  8. customThe resulting solid was triturated with MeOH/H2O (1:1, 1 L)
  9. filtrationthen filtered
  10. washwashed with additional MeOH/H2O (1:1, 500 mL)
  11. customdried in a vacuum oven at about 50-60° C. for about 16 hours

Sources & evidence

ORD record
ord-727befa995a94491939456222af2c0e3
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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