Diisopropylethylamine → N-[1-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]-2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanamide

HRID 1754365Notes

Reaction equation

HRID 1754365 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13]([CH3:15])[CH3:14])=[C:11]([NH2:16])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:17][C:18]1[N:22]([CH:23]([CH3:27])[C:24](O)=[O:25])[N:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[N:19]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([CH:13]([CH3:14])[CH3:15])=[C:11]([NH:16][C:24](=[O:25])[CH:23]([N:22]3[C:18]([CH3:17])=[N:19][C:20]([C:28]([F:29])([F:30])[F:31])=[N:21]3)[CH3:27])[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 664259211-(4-chlorophenyl)-5-(propan-2-yl)-1H-pyrazol-4-amineHCID 867116872-[5-Methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanoic acid

Product 1

HCID 76902963N-[1-(4-chlorophenyl)-5-isopropylpyrazol-4-yl]-2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanamideYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-chlorophenyl)-5-isopropylpyrazol-4-amine (0.054 g, 0.23 mmol) in DMF (1.0 mL) was added 2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanoic acid (0.051 g, 0.23 mmol), followed by diisopropylethylamine (0.059 g, 0.46 mmol) and HATU (0.105 g, 0.28 mmol). After stirring at room temperature for 1 h, the reaction was diluted with water and the aqueous layer was extracted with ethyl acetate (2×5 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting crude product was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.025 g, 0.057 mmol, 25%). 1H NMR (400 MHz, CDCl3) δ 8.25 (s, 1H), 8.03 (d, J=0.6 Hz, 1H), 7.49-7.41 (m, 2H), 7.32-7.23 (m, 2H), 5.12 (q, J=7.2 Hz, 1H), 3.02 (m, 1H), 2.61 (s, 3H), 1.92 (d, J=7.2 Hz, 3H), 1.27 (d, J=7.2 Hz, 3H), 1.10 (d, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C19H20ClF3N6O [M+H]+ 441.1, found 440.9.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate (2×5 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude product was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-dc888aa372a9448b96452698b627c61a
Source dataset
uspto-grants-2015_10
Patent number
US09169248B2

Reaction notes

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