Diisopropylethylamine → HCID 76902775, compound

HRID 1754359Notes

Reaction equation

HRID 1754359 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[C:11]([NH2:19])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Cl:20][C:21]1[C:22]([C:31]([F:34])([F:33])[F:32])=[N:23][N:24]([CH2:27][C:28](O)=[O:29])[C:25]=1[CH3:26].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:20][C:21]1[C:22]([C:31]([F:33])([F:32])[F:34])=[N:23][N:24]([CH2:27][C:28]([NH:19][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[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:29])[C:25]=1[CH3:26]

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 86724371HCID 86724371, compound

Product 1

HCID 76902775HCID 76902775, compoundYield 37.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-fluorophenyl)-5-phenylpyrazol-4-amine (0.03 g, 0.12 mmol) in DMF (1.0 mL) was added 2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetic acid (0.024 g, 0.12 mmol), followed by diisopropylethylamine (0.031 g, 0.24 mmol) and HATU (0.055 g, 0.14 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 (0.020 g, 0.045 mmol, 28%). 1H NMR (400 MHz, CDCl3) δ 8.29 (s, 1H), 7.55 (s, 1H), 7.44-7.34 (m, 3H), 7.22-7.14 (m, 2H), 7.07-6.93 (m, 4H), 4.86 (s, 2H), 2.29 (s, 3H); MS: (ES) m/z calculated for C22H16ClF4N5O [M+H]+ 478.1, found 477.8.

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-4603e309bfa44921ac33ae1563c5ead7
Source dataset
uspto-grants-2015_10
Patent number
US09169248B2

Reaction notes

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