Potassium Carbonate → HCID 11963306, compound

HRID 415919Notes

Reaction equation

HRID 415919 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[C:34]4[C:29](=[CH:30][C:31]([O:37][CH3:38])=[C:32]([O:35][CH3:36])[CH:33]=4)[N:28]=[CH:27][CH:26]=3)=[C:20]([F:39])[CH:19]=2)=[O:16])[C:5](=[O:14])[N:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:46]1(B(O)O)[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>CN(C=O)C.O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:36][O:35][C:32]1[CH:33]=[C:34]2[C:29](=[CH:30][C:31]=1[O:37][CH3:38])[N:28]=[CH:27][CH:26]=[C:25]2[O:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:15]([C:4]2[C:5](=[O:14])[N:6]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:7]=[C:2]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH:3]=2)=[O:16])=[CH:19][C:20]=1[F:39]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 59598405HCID 59598405, compound

Product 1

HCID 11963306HCID 11963306, compoundYield 92.3%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

5-Bromo-N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-2-oxo-1-phenyl-1,2-dihydro-pyridine-3-carboxamide (0.075 g, 0.13 mmol) was suspended in DMF (1.5 mL) and then was added a solution of potassium carbonate (0.053 g, 0.38 mmol) in water (0.5 mL), phenylboronic acid (0.015 g, 0.13 mmol) and PdCl2(dppf)2 (0.0093 g, 0.013 mmol). The reaction mixture was heated at 80° C. for 6 hours. The reaction mixture was diluted with ethyl acetate and water then extracted with ethyl acetate. The organic layer was washed with brine then dried over sodium sulfate and concentrated under vacuum. The remaining residue was purified by silica gel chromatography (1% methanol/dichloromethane to 2% methanol/dichloromethane) to give N-(4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl)-2-oxo-1,5-diphenyl-1,2-dihydropyridine-3-carboxamide as a light yellow solid (0.069 g, 0.12 mmol, 92% yield). MS (ESI pos. ion) m/z: 588 (MH+). Calc'd exact mass for C35H26FN3O5: 587. 1H NMR (400 MHz, DMSO-d6) 12.19 (s, 1 H), 8.87 (d, J=2.91 Hz, 1 H), 8.40-8.55 (m, 2 H), 8.09 (dd, J=12.82, 2.34 Hz, 1 H), 7.75 (d, J=7.33 Hz, 2 H), 7.16-7.67 (m, 12 H), 6.49 (d, J=5.05 Hz, 1 H), 3.95 (s, 6 H).

Workup

  1. extractionthen extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialthen dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe remaining residue was purified by silica gel chromatography (1% methanol/dichloromethane to 2% methanol/dichloromethane)

Sources & evidence

ORD record
ord-a19baae9bfb64ff38d795d0e01df18df
Source dataset
uspto-grants-2012_01
Patent number
US08088794B2

Reaction notes

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