Dichloromethane → methyl 5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylate

HRID 1402491Notes

Reaction equation

HRID 1402491 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][C:25]=2[F:26])[C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=2[F:22])=[O:13])[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:35]2[NH:39][CH:38]=[C:37]([C:40]([O:42][CH3:43])=[O:41])[CH:36]=2)O1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O.O1CCOCC1>[F:26][C:25]1[CH:24]=[CH:23][C:11]([C:12]([NH:14][C:15]2[CH:20]=[C:19]([CH3:21])[CH:18]=[CH:17][C:16]=2[F:22])=[O:13])=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:35]2[NH:39][CH:38]=[C:37]([C:40]([O:42][CH3:43])=[O:41])[CH:36]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 53405106Methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-pyrrole-3-carboxylateHCID 866515583-(2-Chloropyridin-4-yloxy)-4-fluoro-N-(2-fluoro-5-methylphenyl)benzamide

Product 1

HCID 51001539methyl 5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(2-Chloropyridin-4-yloxy)-4-fluoro-N-(2-fluoro-5-methylphenyl)benzamide (1.217 g, 3.25 mmol), methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-3-carboxylate (1.63 g, 6.50 mmol) and potassium carbonate (0.67 g, 4.87 mmol) in water (2.5 mL) and dioxane (15 mL) was purged with nitrogen for several minutes. To the mixture was added tetrakis-triphenylphosphine palladium(0) (0.18 g, (0.16 mmol). The reaction was sealed under nitrogen and heated at 100° C. for 15 h. The cooled reaction was mixed with dichloromethane and filtered through Celite. The red solution was evaporated. The resulting oil was dissolved in dichloromethane, put on a column of silica gel (80 g) and eluted with hexane/EtOAc (1:1) to afford methyl 5-[4-(2-fluoro-5-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrole-3-carboxylate as white solid. Yield: 1.162 g, 77%.

Workup

  1. customwas purged with nitrogen for several minutes
  2. additionTo the mixture was added tetrakis-triphenylphosphine palladium(0) (0.18 g, (0.16 mmol)
  3. customThe reaction was sealed under nitrogen
  4. customThe cooled reaction
  5. filtrationfiltered through Celite
  6. customThe red solution was evaporated
  7. dissolutionThe resulting oil was dissolved in dichloromethane
  8. washeluted with hexane/EtOAc (1:1)

Sources & evidence

ORD record
ord-783b09c0ae3a4bfab4d38483d333f5c1
Source dataset
uspto-grants-2014_12
Patent number
US08906944B2

Reaction notes

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