Triethylamine → 5-methyl-1H-pyrazole-4-carboxylic acid [(S)-1-(3-trifluoromethyl-phenyl)-ethyl]-amide

HRID 2067962Notes

Reaction equation

HRID 2067962 reaction equation
[CH3:1][C:2]1[NH:6][N:5]=[CH:4][C:3]=1[C:7]([OH:9])=O.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[F:44][C:45]([F:56])([F:55])[C:46]1[CH:47]=[C:48]([C@@H:52]([NH2:54])[CH3:53])[CH:49]=[CH:50][CH:51]=1>CN(C=O)C.[Cl-].[NH4+]>[F:44][C:45]([F:55])([F:56])[C:46]1[CH:47]=[C:48]([C@@H:52]([NH:54][C:7]([C:3]2[CH:4]=[N:5][NH:6][C:2]=2[CH3:1])=[O:9])[CH3:53])[CH:49]=[CH:50][CH:51]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5576005-methyl-1H-pyrazole-4-carboxylic acidHCID 7023585(1S)-1-[3-(Trifluoromethyl)phenyl]ethylamine

Product 1

HCID 584434065-methyl-1H-pyrazole-4-carboxylic acid [(S)-1-(3-trifluoromethyl-phenyl)-ethyl]-amideYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To 5-methyl-1H-pyrazole-4-carboxylic acid (390 mg, 3.1 mmol) in DMF (10 mL) is added triethylamine (1.2 mL, 9.4 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (PyBOP) (1.8 g, 3.5 mmol). After stirring for 5 min at room temperature, (S)-1-(3-trifluoromethyl-phenyl)-ethylamine (650 mg, 3.4 mmol) is added and the reaction is stirred at room temperature for 2 days. The mixture is then diluted with saturated ammonium chloride and extracted with EtOAc (4×15 mL). The combined organic layer is washed with saturated NaHCO3 solution (20 mL) followed by brine (20 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude material is purified by flash chromatography on silica gel (eluted with 0 to 60% EtOAc/hexanes) followed by recrystallization from ether/hexanes to provide 5-methyl-1H-pyrazole-4-carboxylic acid [(S)-1-(3-trifluoromethyl-phenyl)-ethyl]-amide as a colorless solid (770 mg, 84%).

Workup

  1. stirringthe reaction is stirred at room temperature for 2 days
  2. extractionextracted with EtOAc (4×15 mL)
  3. washThe combined organic layer is washed with saturated NaHCO3 solution (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material is purified by flash chromatography on silica gel (eluted with 0 to 60% EtOAc/hexanes)
  8. customfollowed by recrystallization from ether/hexanes

Sources & evidence

ORD record
ord-085b5ed476c0431f8afa6a3c4abbbee7
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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