Acetic Acid → HCID 9880611, compound

HRID 396408Notes

Reaction equation

HRID 396408 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([CH3:13])=[C:11]([C:14](=O)[CH3:15])[CH:10]=[N:9]2)[CH:5]=[CH:6][CH:7]=1.CC([O-])(C)C.[K+].[C:23](OCC)(=O)[C:24]([O:26][CH2:27][CH3:28])=[O:25].O.[NH2:34][NH2:35].C(O)(=O)C>C1COCC1.C(O)C>[CH2:27]([O:26][C:24]([C:23]1[NH:35][N:34]=[C:14]([C:11]2[CH:10]=[N:9][N:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[C:12]=2[CH3:13])[CH:15]=1)=[O:25])[CH3:28]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 7268Diethyl OxalateHCID 24654Hydrazine hydrate (1:1)HCID 2805558HCID 2805558, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 9880611HCID 9880611, compoundYield 12.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 47 mg (0.2 mmol) of 1-[1-(3-chlorophenyl)-5-methyl-1H-pyrazol-4-yl]ethan-1-one (commercially available) in 2 mL of THF was added successively 0.4 mL (0.4 mmol) of 1M KOtBu in THF and 54 μL (0.4 mmol) of diethyl oxalate. The mixture was stirred at room temperature overnight, quenched with water, and diluted with ethyl acetate. The solution was washed successively with saturated aqueous ammonium chloride, saturated aqueous sodium bicarbonate, and brine, dried over sodium sulfate, and concentrated in vacuo. The residue was diluted with 2 mL of ethanol, and 15 mL (0.3 mmol) of hydrazine monohydrate was added followed by 15 mL (0.3 mmol) of acetic acid. The mixture was stirred at room temperature for 2 hours, and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC to afford 8 mg of the title compound as the trifluoroacetic acid salt. MS m/e expected M+1 333.18, found m/e 333.01. 1H NMR (DMSO-d6) δ 14.0 (s, 0.45H), 13.8 (s, 0.55H), 8.05 (s, 1H), 7.75 (s, 1H), 7.55 (m, 3H), 7.1 (br s, 0.45H), 6.8 (br s, 0.55H), 4.3 (br s, 2H), 2.65 (br s, 1.4H), 2.4 (br s, 1.6H), 1.3 (t, 3H).

Workup

  1. customquenched with water
  2. additiondiluted with ethyl acetate
  3. washThe solution was washed successively with saturated aqueous ammonium chloride, saturated aqueous sodium bicarbonate, and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. additionwas added
  7. stirringThe mixture was stirred at room temperature for 2 hours
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-84bdb1e5b7484ecd8d8d9f80fe35d6ab
Source dataset
uspto-grants-2003_08
Patent number
US06608087B1

Reaction notes

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