Diisopropylethylamine → ethyl 5-(2-chloro-4-fluoro-5-(pyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate

HRID 522116Notes

Reaction equation

HRID 522116 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:18][C:19]1[N:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:22]=[C:21]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:20]=1.C(N(CC)C(C)C)(C)C.CCCP(=O)=O>CC1CCCO1>[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([NH:18][C:19]1[N:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:22]=[C:21]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:20]=1)=[O:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 23630921Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylateHCID 1184971152-Chloro-4-fluoro-5-(pyridin-2-yl)benzoic acid

Product 1

HCID 118497085ethyl 5-(2-chloro-4-fluoro-5-(pyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylateYield 299.7%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To a refluxing mixture of 2-chloro-4-fluoro-5-(pyridin-2-yl)benzoic acid (Preparation 22A, 9.2 g, 36.6 mmol), ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (8.45 g, 36.6 mmol), N,N-diisopropylethylamine (19.2 mL, 110 mmol) and 2-methyltetrahydrofuran (320 mL), was added propylphosphonic anhydride solution (255 mL, 429 mmol, >50% by weight in EtOAc) dropwise under argon, and the reaction maintained at reflux for 5 hours. After cooling to room temperature, the reaction was filtered and the filtrate concentrated in vacuo. The residue was dissolved in ethyl acetate (350 mL) and washed with saturated aqueous sodium hydrogen carbonate solution (300 mL). The organic layer was filtered under vacuum and the solids washed with EtOAc (20 mL) and TBME (200 mL) to give the title compound (51 g, 78%).

Workup

  1. temperaturethe reaction maintained
  2. temperatureat reflux for 5 hours
  3. filtrationthe reaction was filtered
  4. concentrationthe filtrate concentrated in vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate (350 mL)
  6. washwashed with saturated aqueous sodium hydrogen carbonate solution (300 mL)
  7. filtrationThe organic layer was filtered under vacuum
  8. washthe solids washed with EtOAc (20 mL) and TBME (200 mL)

Sources & evidence

ORD record
ord-45d0c9e1fc1c4f2893112d6d22bf3260
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

Loading…