Diisopropylethylamine → HCID 76902960, compound

HRID 1754367Notes

Reaction equation

HRID 1754367 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.[Cl:17][C:18]1[C:19]([C:30]([F:33])([F:32])[F:31])=[N:20][N:21]([C:24]([CH3:29])([CH3:28])[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:30]([F:32])([F:31])[F:33])=[N:20][N:21]([C:24]([CH3:29])([CH3:28])[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[CH:13]([CH3:14])[CH3:15])=[O:26])[C:22]=1[CH3:23]

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 86711672HCID 86711672, compound

Product 1

HCID 76902960HCID 76902960, compoundYield 39%

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-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-2-methyl-propanoic acid (0.037 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 (0.025 g, 0.053 mmol, 39%). 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J=0.6 Hz, 1H), 7.33-7.25 (m, 2H), 7.20-7.10 (m, 2H), 6.61 (s, 1H), 2.92 (m, 1H), 2.37 (s, 3H), 1.97 (s, 6H), 1.03 (d, J=7.1 Hz, 6H); MS: (ES) m/z calculated for C21H22ClF4N5O [M+H]+ 472.1, found 471.9.

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-a93cec7a46c2404a80f74212efbc00cf
Source dataset
uspto-grants-2015_10
Patent number
US09169248B2

Reaction notes

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