Potassium Carbonate → N-(2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1472614Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1472614
[F:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)[CH:11]=2)[C:6]([F:22])=[CH:5][C:3]=1[NH2:4].C([O-])([O-])=O.[K+].[K+].[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42](Cl)=[O:43])[C:37]2=[O:45])=[CH:32][CH:31]=1>CCOC(C)=O.O.C(Cl)Cl>[F:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]3[CH:17]=[N:18][N:19]([CH3:21])[CH:20]=3)[CH:11]=2)[C:6]([F:22])=[CH:5][C:3]=1[NH:4][C:42]([C:38]1[C:37](=[O:45])[N:36]([C:33]2[CH:32]=[CH:31][C:30]([F:29])=[CH:35][CH:34]=2)[CH:41]=[CH:40][CH:39]=1)=[O:43]

Komponenten

7

Edukt 3

HCID 11430Potassium Carbonate2×HCID 593227742,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)anilineHCID 596809561-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chloride2×

Produkt 1

HCID 90425853N-(2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamideAusbeute 180,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel2×HCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

A mixture of Example A2 (0.324, 1.073 mmol) and K2CO3 (0.178 g, 1.288 mmol) in EtOAc (1.4 mL) and H2O (2.15 mL) was stirred vigorously for 5 min, treated with a solution of Example A3 (0.108 g, 0.429 mmol) in EtOAc (1.4 mL) and stirred at RT for 2 h. The layers were separated, the aqueous layer extracted with DCM and the combined organics were dried over Na2SO4 and concentrated to dryness. The residue was combined with K2CO3 (0.265 g, 1.920 mmol) in DCM (1.4 mL) and H2O (2.1 mL), stirred vigorously for 5 min, treated with a solution of Example A3 (0.403 g, 1.60 mmol) in DCM (1.4 mL) and stirred at RT overnight. The layers were separated, the aqueous layer extracted with DCM and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(2,5-difluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (400 mg, 72%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 12.43 (s, 1H), 8.60 (dd, J=7.3, 2.2 Hz, 1H), 8.55 (dd, J=12.6, 7.2 Hz, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 8.15 (dd, J=6.6, 2.2 Hz, 1H), 7.97 (s, 1H), 7.62-7.56 (m, 3H), 7.41 (m, 2H), 7.25 (d, J=2.4 Hz, 1H), 6.76-6.71 (m, 2H), 3.84 (s, 3H); MS (ESI) m/z: 518.1 (M+H+).

Aufarbeitung

  1. customThe layers were separated
  2. extractionthe aqueous layer extracted with DCM
  3. dry with materialthe combined organics were dried over Na2SO4
  4. concentrationconcentrated to dryness
  5. stirringstirred vigorously for 5 min
  6. stirringstirred at RT overnight
  7. customThe layers were separated
  8. extractionthe aqueous layer extracted with DCM
  9. dry with materialthe combined organics were dried over Na2SO4
  10. concentrationconcentrated to dryness
  11. custompurified via silica gel chromatography (MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-70835506d7db4ccc955f0be652bedd51
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012635B2

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