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

HRID 1754363Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1754363
[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:29]([F:32])([F:31])[F:30])=[N:20][N:21]([CH:24]([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:29]([F:31])([F:30])[F:32])=[N:20][N:21]([CH:24]([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]

Komponenten

7

Edukt 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 170245572-[4-chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]propanoic acidHCID 664257241-(4-Fluorophenyl)-5-isopropyl-pyrazol-4-amine

Produkt 1

HCID 769031522-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-N-[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]propanamideAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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]propanoic acid (0.035 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 (0.020 g, 0.044 mmol, 32%). 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 8.02 (s, 1H), 7.34-7.24 (m, 2H), 7.21-7.11 (m, 2H), 5.05 (q, J=7.2 Hz, 1H), 3.03-2.91 (m, 1H), 2.38 (s, 3H), 1.90 (d, J=7.2 Hz, 3H), 1.25 (dd, J=13.9, 7.1 Hz, 3H), 1.08 (d, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C20H20ClF4N5O [M+H]+ 458.1, found 457.9.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-698e275e22ab4655a3659f68aa99ccaf
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169248B2

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