Diisopropylethylamine → 2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-N-[1-(4-fluorophenyl)-5-methylpyrazol-4-yl]acetamide

HRID 1754355Notes

Reaction equation

HRID 1754355 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13](C)C)=[C:11]([NH2:16])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Cl:17][C:18]1[C:19]([C:28]([F:31])([F:30])[F:29])=[N:20][N:21]([CH2:24][C:25](O)=[O:26])[C:22]=1[CH3:23].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:17][C:18]1[C:19]([C:28]([F:30])([F:29])[F:31])=[N:20][N:21]([CH2:24][C:25]([NH:16][C:11]2[CH:10]=[N:9][N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:12]=2[CH3:13])=[O:26])[C:22]=1[CH3:23]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1876853(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 664257241-(4-Fluorophenyl)-5-isopropyl-pyrazol-4-amine

Product 1

HCID 867243702-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-N-[1-(4-fluorophenyl)-5-methylpyrazol-4-yl]acetamideYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-fluorophenyl)-5-isopropylpyrazol-4-amine (0.03 g, 0.16 mmol) in DMF (1.0 mL) was added 2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetic acid (0.038 g, 0.16 mmol), followed by diisopropylethylamine (0.042 g, 0.32 mmol) and HATU (0.067 g, 0.18 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 (0.02 g, 0.048 mmol, 30%). 1H NMR (400 MHz, CDCl3) δ 7.93 (s, 1H), 7.37 (dd, J=8.9, 4.7 Hz, 1H), 7.26 (d, J=0.4 Hz, 2H), 7.18 (dd, J=8.9, 8.1 Hz, 2H), 4.94 (s, 2H), 2.39 (s, 3H), 2.16 (s, 3H); MS: (ES) m/z calculated for C17H14ClF4N5O [M+H]+416.1, found 416.0.

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-237092f65c544f8589282e109e8759ff
Source dataset
uspto-grants-2015_10
Patent number
US09169248B2

Reaction notes

Loading…