Diisopropylethylamine → ethyl 5-(2,4-dichloro-5-(5-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate

HRID 522115Notes

Reaction equation

HRID 522115 reaction equation
Cl.[Cl:2][C:3]1[CH:11]=[C:10]([Cl:12])[C:9]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=2)=[CH:8][C:4]=1[C:5]([OH:7])=O.[NH2:20][C:21]1[N:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:24]=[C:23]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:22]=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CCOC(C)=O>[Cl:2][C:3]1[CH:11]=[C:10]([Cl:12])[C:9]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=2)=[CH:8][C:4]=1[C:5]([NH:20][C:21]1[N:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:24]=[C:23]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:22]=1)=[O:7]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 23630921Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylateHCID 1184970762,4-Dichloro-5-(5-fluoropyridin-2-yl)benzoic acid hydrochloride

Product 1

HCID 118497079ethyl 5-(2,4-dichloro-5-(5-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylateYield 55.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

2,4-dichloro-5-(5-fluoropyridin-2-yl)benzoic acid hydrochloride (Preparation 20, 900 mg, 3.15 mmol), ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (683 mg, 2.95 mmol) and diisopropylethylamine (3.28 mL, 18.88 mmol) were added to EtOAc (30 mL) and heated to reflux under an atmosphere of nitrogen. A 50% solution of propylphosphonic cyclic anhydride in EtOAc (9 g, 14.16 mmol) was added dropwise, and the reaction was kept at reflux for 3 hours. After cooling, the reaction was basified with saturated aqueous sodium hydrogen carbonate solution. The organic layer was collected, dried over magnesium sulphate and concentrated in vacuo. The residue was dissolved in ethanol (30 mL) and solid sodium carbonate (˜2 g) was added with rapid stirring for 1 hour. The mixture was filtered and the filtrate concentrated in vacuo. The residue was stirred with dilute aqueous sodium hydrogen carbonate, filtered, washed with water and dried in vacuo. The resulting solid was triturated with TBME to afford the title compound (822 mg, 52%).

Workup

  1. temperatureheated
  2. temperatureto reflux under an atmosphere of nitrogen
  3. temperatureat reflux for 3 hours
  4. temperatureAfter cooling
  5. customThe organic layer was collected
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in ethanol (30 mL)
  9. additionsolid sodium carbonate (˜2 g) was added
  10. filtrationThe mixture was filtered
  11. concentrationthe filtrate concentrated in vacuo
  12. stirringThe residue was stirred with dilute aqueous sodium hydrogen carbonate
  13. filtrationfiltered
  14. washwashed with water
  15. customdried in vacuo
  16. customThe resulting solid was triturated with TBME

Sources & evidence

ORD record
ord-bc8021391543457cada4beecfdd1e240
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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