Diisopropylethylamine → N-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]butanamide

HRID 1754360Notes

Reaction equation

HRID 1754360 reaction equation
[F: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:19]([CH:27]([CH2:31][CH3:32])[C:28](O)=[O:29])[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=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>[F: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:28](=[O:29])[CH:27]([N:19]3[CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[N:22]=[C:18]3[CH3:17])[CH2:31][CH3:32])[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 664257241-(4-Fluorophenyl)-5-isopropyl-pyrazol-4-amineHCID 867116782-[2-Methyl-4-(trifluoromethyl)imidazol-1-yl]butanoic acid

Product 1

HCID 76903345N-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]butanamideYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-fluorophenyl)-5-isopropylpyrazol-4-amine (0.03 g, 0.14 mmol) in DMF (1.0 mL) was added 2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]butanoic acid (0.032 g, 0.14 mmol), followed by diisopropylethylamine (0.042 g, 0.32 mmol) and HATU (0.057 g, 0.15 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 (0.015 g, 0.034 mmol, 25%). 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.47 (q, J=1.2 Hz, 1H), 7.34-7.24 (m, 2H), 7.21-7.11 (m, 2H), 6.98 (s, 1H), 4.65 (dd, J=10.1, 5.3 Hz, 1H), 3.00-2.88 (m, 1H), 2.49 (ddd, J=14.4, 7.4, 5.3 Hz, 1H), 2.45 (s, 3H), 2.13-2.00 (m, 1H), 1.11-0.97 (m, 9H); MS: (ES) m/z calculated for C21H23F4N5O [M+H]+ 438.2, found 438.0.

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-d36676204b13403e91b478cc0b391951
Source dataset
uspto-grants-2015_10
Patent number
US09169248B2

Reaction notes

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