Acetic Acid → 2-{[3-(4-fluorophenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid

HRID 915579Notes

Reaction equation

HRID 915579 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([NH2:13])[N:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH3:20])[N:9]=2)=[CH:4][CH:3]=1.I[C:22]1[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=1[C:24]([OH:26])=[O:25].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C>CN(C=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:12]=[C:11]([NH:13][C:22]3[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=3[C:24]([OH:26])=[O:25])[N:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[CH3:20])[N:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 69412-Iodobenzoic acidHCID 11430Potassium CarbonateHCID 162282833-(4-fluorophenyl)-1-(2-methylphenyl)-1H-pyrazol-5-amine2×

Product 1

HCID 100457462-{[3-(4-fluorophenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acidYield 12%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 3-(4-fluorophenyl)-1-(2-methylphenyl)-1H-pyrazol-5-amine (Intermediate D, 100 mg, 0.37 mmol) in DMF (3 mL), was added 2-iodobenzoic acid (93 mg, 0.37 mmol), potassium carbonate (62 mg, 0.45 mmol), and copper (II) acetate (3 mg, 0.01 mmol). The mixture was stirred at 150° C. for 18 h and then cooled to rt. The solution was adjusted to pH 4 using glacial acetic acid. The mixture was extracted with dichloromethane (3×5 mL), and then the combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by HPLC (45-90% acetonitrile in water) to afford the title compound (17 mg, 12%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 2.08 (s, 3H), 6.85 (ddd, 1H), 6.93 (s, 1H), 7.24 (ddd, 2H), 7.42 (m, 6H), 7.84 (dd, 1H), 7.92 (ddd, 2H), 10.02 (s, 1H), 13.23 (s, 1H); ES-MS m/z 388.2 (MH+); HPLC RT (min) 3.47.

Workup

  1. temperaturecooled to rt
  2. extractionThe mixture was extracted with dichloromethane (3×5 mL)
  3. washthe combined organic extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by HPLC (45-90% acetonitrile in water)

Sources & evidence

ORD record
ord-61f6c18bfad8473c92842664fea8a530
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

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