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 1472614Notes

Reaction equation

HRID 1472614 reaction equation
[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]

Participants

7

Reactant 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×

Product 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-carboxamideYield 180.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-70835506d7db4ccc955f0be652bedd51
Source dataset
uspto-grants-2015_04
Patent number
US09012635B2

Reaction notes

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