Diisopropylethylamine → 1-[1-(4-chlorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propan-1-one

HRID 710680Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 710680
[CH3:1][C:2]1[N:6]([CH:7]([CH3:11])[C:8]([OH:10])=O)[N:5]=[C:4]([C:12]([F:15])([F:14])[F:13])[N:3]=1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:31]3[CH2:30][CH2:29][CH2:28][NH:27][C:26]=3[CH:25]=[N:24]2)=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([N:23]2[C:31]3[CH2:30][CH2:29][CH2:28][N:27]([C:8](=[O:10])[CH:7]([N:6]4[C:2]([CH3:1])=[N:3][C:4]([C:12]([F:15])([F:14])[F:13])=[N:5]4)[CH3:11])[C:26]=3[CH:25]=[N:24]2)=[CH:21][CH:22]=1

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 680410521-(4-chlorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridineHCID 867116872-[5-Methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanoic acid

Produkt 1

HCID 733362111-[1-(4-chlorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propan-1-oneAusbeute 30 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of 2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanoic acid (0.048 g, 0.21 mmol) and 1-(4-chlorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine (0.050 g, 0.21 mmol) in DMF (1 mL) were added Hunig's base (0.055 g, 0.42 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uranium hexafluorophosphate methanaminium (HATU) (0.090 g, 0.23 mmol). The mixture was stirred at room temperature for 1 hour, and then partitioned between water (4 mL) and ethyl acetate (6 mL). The organic layer was washed with brine, dried (Na2SO4), filtered, concentrated in vacuo, and purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the desired product as a white solid (0.028 g, 0.063 mmol, 30%). 1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.43 (s, 4H), 5.60 (q, J=7.1 Hz, 1H), 3.77 (ddd, J=12.6, 7.5, 3.0 Hz, 1H), 3.52 (ddd, J=12.3, 8.3, 3.0 Hz, 1H), 2.84 (tt, J=6.9, 3.3 Hz, 2H), 2.52 (s, 3H), 2.09-1.81 (m, 5H); MS: (ES) m/z calculated for C19H18ClF3N6O [M+H]+ 439.1, found 438.9.

Aufarbeitung

  1. custompartitioned between water (4 mL) and ethyl acetate (6 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Quellen und Nachweise

ORD-Eintrag
ord-7cb17d4e5dd148fd97cf985ac5712e10
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181241B2

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