4-Hydrazinobenzoic acid → 4-(6-fluoro-3-oxo-1,3-dihydro-2H-pyrazolo[4,3-c]cinnolin-2-yl)benzoic acid

HRID 1178252Notes

Reaction equation

HRID 1178252 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[N:9][C:8]([C:12]([O-:14])=O)=[C:7]2O.[NH:16]([C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=1)[NH2:17]>S(Cl)(Cl)=O.C(O)C>[F:1][C:2]1[C:11]2[N:10]=[N:9][C:8]3[C:12](=[O:14])[N:16]([C:18]4[CH:19]=[CH:20][C:21]([C:22]([OH:24])=[O:23])=[CH:25][CH:26]=4)[NH:17][C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 120894-Hydrazinobenzoic acidHCID 178524933HCID 178524933, compound

Product 1

HCID 589748824-(6-fluoro-3-oxo-1,3-dihydro-2H-pyrazolo[4,3-c]cinnolin-2-yl)benzoic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 24386Thionyl ChlorideSolvent

Procedure

Crude 8-Fluoro-4-hydroxycinnoline-3-carboxylate from the previous stage (1.00 g, 4.95 mmol) was dissolved in thionyl chloride (50 ml). The solution was heated to reflux for 2-3 h until no further gas evolution was observed. The reaction mixture was cooled to room temperature and excess thionyl chloride was removed under vacuum. The crude intermediate was azeotroped with toluene (3×25 ml). A dark brown solid was obtained, which was taken up in ethanol (25 ml). 4-Hydrazinobenzoic acid (640 mg, 4.21 mmol) was added and the mixture was stirred at room temperature overnight. The solids were collected by filtration, slurried in 1 M HCl (100 ml), filtered, washed with hexane (50 ml) and dried under vacuum. A brown solid was obtained (890 mg of crude product). LCMS: m/z [M+H]+ 325.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 2-3 h until no further gas evolution
  3. customexcess thionyl chloride was removed under vacuum
  4. customThe crude intermediate was azeotroped with toluene (3×25 ml)
  5. customA dark brown solid was obtained
  6. filtrationThe solids were collected by filtration
  7. filtrationfiltered
  8. washwashed with hexane (50 ml)
  9. customdried under vacuum

Sources & evidence

ORD record
ord-f5d5626fa4304d6bb08ae02aad4edc58
Source dataset
uspto-grants-2007_10
Patent number
US07276505B2

Reaction notes

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