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

HRID 522117Notes

Reaction equation

HRID 522117 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[C:8]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.[NH2:19][C:20]1[N:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:23]=[C:22]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:21]=1.C(N(CC)C(C)C)(C)C.CC1CCCO1.CCCP(=O)=O>O>[Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[C:8]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([NH:19][C:20]1[N:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:23]=[C:22]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH:21]=1)=[O:6]

Participants

7

Reactant 5

HCID 73012-MethyltetrahydrofuranHCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 23630921Ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylateHCID 1184971172,4-Dichloro-5-(3-fluoropyridin-2-yl)benzoic acid

Product 1

HCID 118497121ethyl 5-(2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a refluxing mixture of 2,4-dichloro-5-(3-fluoropyridin-2-yl)benzoic acid (Preparation 27A, 159 g, 0.554 mol), ethyl 5-amino-1-phenyl-1H-pyrazole-3-carboxylate (154 g, 0.665 mol), N,N-diisopropylethylamine (215 g, 1.66 mol) and 2-methyltetrahydrofuran (4.8 L), was added propylphosphonic anhydride solution (989 mL, 1.66 mol, >50% by weight in EtOAc) and the reaction maintained at reflux for 6 hours. After cooling to room temperature, the reaction was diluted with water (6 L) and extracted with 2-methyltetrahydrofuran (2×1.5 L). The combined organic layers were concentrated in vacuo to provide a slurry which was filtered and the solid washed with ethyl acetate (3×200 mL) to give the title compound as a white solid (215 g, 79%).

Workup

  1. temperaturethe reaction maintained
  2. temperatureat reflux for 6 hours
  3. extractionextracted with 2-methyltetrahydrofuran (2×1.5 L)
  4. concentrationThe combined organic layers were concentrated in vacuo
  5. customto provide a slurry which
  6. filtrationwas filtered
  7. washthe solid washed with ethyl acetate (3×200 mL)

Sources & evidence

ORD record
ord-42009cfa486d4cdaa094c1f57d60d3ea
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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