Acetic Acid → 3-(4-Amino-6-methyl-1H-indazol-1-yl)benzoic acid

HRID 1925593Notes

Reaction equation

HRID 1925593 reaction equation
Br[C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15]([OH:17])=[O:16].Cl.C(O)(=O)C.[NH3:26]>[Cu]I>[NH2:26][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15]([OH:17])=[O:16]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 222AmmoniaHCID 313Hydrochloric AcidHCID 576726453-(4-Bromo-6-methyl-1H-indazol-1-yl)benzoic acid

Product 1

HCID 576726463-(4-Amino-6-methyl-1H-indazol-1-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
20 °C

Procedure

A suspension of 3-(4-bromo-6-methyl-1H-indazol-1-yl)benzoic acid (1450.5 g, 4.38 mol) and copper (I) iodide (42.47 g, 0.22 mol, 5 mol %) in aqueous ammonia (0.88 sg, 13.5 L) was heated in a sealed pressure vessel until a pressure of 7 Bar±0.3 Bar was generated (contents temperature ˜78° C.). Stirring was continued for a period of ca. 2 days. The reaction mixture was cooled to 20° C. and then charged in to a Controlled Lab Reactor fitted with a 5M HCl scrubber. The solution was heated at reflux to remove excess ammonia by gradually raising the contents temperature to >90° C.—end point pH 7.87. The reaction mixture was then cooled to 60±3° C. and acetic acid (725 mL, 12.7 mol) was added slowly to form a precipitate−end point pH=5.68. The batch was cooled to 5±3° C. and stirred for 825 minutes. The slurry was filtered and washed with water (3×4.5 L). The solid was dried in vacuo at 50° C. to afford the title compound (1112.3 g).

Workup

  1. temperaturewas heated in a sealed pressure vessel until a pressure of 7 Bar±0.3 Bar
  2. custom(contents temperature ˜78° C.)
  3. additioncharged in to a Controlled Lab Reactor
  4. temperatureThe solution was heated
  5. temperatureat reflux
  6. customto remove excess ammonia
  7. temperatureby gradually raising the contents temperature to >90° C.—end point pH 7.87
  8. temperatureThe reaction mixture was then cooled to 60±3° C.
  9. customto form a precipitate−end point pH=5.68
  10. temperatureThe batch was cooled to 5±3° C.
  11. stirringstirred for 825 minutes
  12. filtrationThe slurry was filtered
  13. washwashed with water (3×4.5 L)
  14. customThe solid was dried in vacuo at 50° C.

Sources & evidence

ORD record
ord-cc490cdd0b8644619953f5fa5a1dab62
Source dataset
uspto-grants-2012_05
Patent number
US08178573B2

Reaction notes

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