Triphenylphosphine → (2E)-N-indol-5-yl-3-[2-(6-methoxy(3-pyridyl))-4-(trifluoromethyl)phenyl]-prop-2-enamide

HRID 730290Notes

Reaction equation

HRID 730290 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1/[CH:12]=[CH:13]/[C:14]([NH:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[CH:20]2)=[O:15].[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][N:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].C(O)C.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]>[NH:22]1[C:23]2[C:19](=[CH:18][C:17]([NH:16][C:14](=[O:15])/[CH:13]=[CH:12]/[C:3]3[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=3[C:31]3[CH:30]=[N:29][C:28]([O:27][CH3:26])=[CH:33][CH:32]=3)=[CH:25][CH:24]=2)[CH:20]=[CH:21]1

Participants

8

Reactant 3

HCID 11776TriphenylphosphineHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 57807978(2E)-3-[2-Bromo-4-(trifluoromethyl)phenyl]-N-indol-5-ylprop-2-enamide

Product 1

HCID 57808012(2E)-N-indol-5-yl-3-[2-(6-methoxy(3-pyridyl))-4-(trifluoromethyl)phenyl]-prop-2-enamide

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (2E)-3-[2-bromo-4-(trifluoromethyl)phenyl]-N-indol-5-ylprop-2-enamide, Example 97, (100 mg, 0.24 mmol), 2-methoxy-5-pyridineboronic acid (60 mg , 0.39 mmol, Digital Specialty Chemicals), tris(dibenzylideneacetone)dipalladium(0) (22 mg, 0.024 mmol, Aldrich) and triphenylphosphine (26 mg, 0.098 mmol, Aldrich) in toluene (1.2 mL), 2.0M aqueous Na2CO3 (0.4 mL) and ethanol (0.4 mL) was stirred at 120° C. overnight. The reaction mixture was filtered through a pad of Celite and diluted with water (50 mL). The aqueous phase was extracted with EtOAc (3×60 mL). The combined extracts were washed with satd NaCl (100 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (gradient: 0-20% EtOAc in hexane) provided the title product as a yellow solid. MP 219-221° C. MS (ESI, pos. ion) m/z: 438 (M+1).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite
  2. additiondiluted with water (50 mL)
  3. extractionThe aqueous phase was extracted with EtOAc (3×60 mL)
  4. washThe combined extracts were washed with satd NaCl (100 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel chromatography (gradient: 0-20% EtOAc in hexane)

Sources & evidence

ORD record
ord-1429f5e670db402697dbe40c7c697ef6
Source dataset
uspto-grants-2009_09
Patent number
US07582657B2

Reaction notes

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