Water → N-{4-[2-Amino-5-(4-hydroxy-3-methoxyphenyl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxamide

HRID 1428102Notes

Reaction equation

HRID 1428102 reaction equation
O.C(=O)([O-])[O-].[K+].[K+].[NH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[C:29](=[O:30])[C:28]([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)=[CH:27][N:26]([CH2:38][C:39]([F:42])([F:41])[F:40])[CH:25]=3)=[O:23])=[CH:17][CH:16]=2)=[CH:13][C:12](Br)=[CH:11][N:10]=1.[CH3:44][O:45][C:46]1[CH:51]=[C:50](B2OC(C)(C)C(C)(C)O2)[CH:49]=[CH:48][C:47]=1[OH:61]>O1CCOCC1.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].ClCCl>[NH2:8][C:9]1[C:14]([C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([C:24]3[C:29](=[O:30])[C:28]([C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)=[CH:27][N:26]([CH2:38][C:39]([F:42])([F:41])[F:40])[CH:25]=3)=[O:23])=[CH:17][CH:16]=2)=[CH:13][C:12]([C:50]2[CH:49]=[CH:48][C:47]([OH:61])=[C:46]([O:45][CH3:44])[CH:51]=2)=[CH:11][N:10]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27346502-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 86700049N-[4-(2-Amino-5-bromopyridin-3-yl)phenyl]-5-(4-fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxamide

Product 1

HCID 86700053N-{4-[2-Amino-5-(4-hydroxy-3-methoxyphenyl)pyridin-3-yl]phenyl}-5-(4-fluorophenyl)-4-oxo-1-(2,2,2-trifluoroethyl)-1,4-dihydropyridine-3-carboxamideYield 42%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Water (0.1 ml), potassium carbonate (70 mg) and [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride-dichloromethane adduct (6.9 mg) were added to a solution of the compound obtained in Step 1 of Example 31 (95 mg) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (51 mg) in 1,4-dioxane (1.5 ml), and the mixture was stirred at 100° C. for four hours. After leaving to cool, the reaction solution was diluted with ethyl acetate. The organic layer was washed with water and brine and dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography [chloroform:methanol=300:1->30:1 (v/v)] to give 43 mg of the title compound as a solid.

Workup

  1. customAfter leaving
  2. temperatureto cool
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe residue was purified by silica gel column chromatography [chloroform:methanol=300:1->30:1 (v/v)]

Sources & evidence

ORD record
ord-acccf00764be4a46ba9ca54c0b30d2cc
Source dataset
uspto-grants-2015_01
Patent number
US08933103B2

Reaction notes

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