Cesium carbonate → 2-(3-fluoro-4-methoxyphenylamino)-N-(4-fluorophenyl)nicotinamide

HRID 2241393Notes

Reaction equation

HRID 2241393 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([F:16])[CH:9]=1.[NH2:17][C:18]1[N:33]=[CH:32][CH:31]=[CH:30][C:19]=1[C:20]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)=[O:21].O1CCOCC1>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:16][C:10]1[CH:9]=[C:8]([NH:17][C:18]2[N:33]=[CH:32][CH:31]=[CH:30][C:19]=2[C:20]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)=[O:21])[CH:13]=[CH:12][C:11]=1[O:14][CH3:15]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 753784-Bromo-2-fluoroanisoleHCID 551366622-amino-N-(4-fluorophenyl)nicotinamide

Product 1

HCID 672215822-(3-fluoro-4-methoxyphenylamino)-N-(4-fluorophenyl)nicotinamideYield 98%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A 1 L round-bottomed flask was charged with cesium carbonate (11.1 g, 34.1 mmol), 4-bromo-2-fluoro-1-methoxybenzene (5.00 g, 24.4 mmol), 2-amino-N-(4-fluorophenyl)nicotinamide (7.61 g, 32.9 mmol), and dioxane (250 mL). The reaction mixture was degassed with nitrogen for 10 minutes, and Xanphos (0.564 g, 0.975 mmol) and Pd2dba3 (0.670 g, 0.732 mmol) were added. The reaction mixture was heated at 90° C. for 48 hours. The reaction mixture was cooled to ambient temperature and diluted with water. The reaction mixture was extracted with EtOAc, dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography (biotage 65) eluting with DCM/MeOH (3%). Isolated 8.50 g (93%) of the product. LRMS M+1 (365.0) observed.

Workup

  1. customThe reaction mixture was degassed with nitrogen for 10 minutes
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. extractionThe reaction mixture was extracted with EtOAc
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel chromatography (biotage 65)
  8. washeluting with DCM/MeOH (3%)

Sources & evidence

ORD record
ord-61aa93d6f3a54d6aa56370336a898934
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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