Triphenylphosphine → (2E)-N-Indol-5-yl-3-[2-(3-pyridylmethyl)-4-(trifluoromethyl)phenyl]prop-2-enamide

HRID 730294Notes

Reaction equation

HRID 730294 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].C([Sn]([CH2:39][C:40]1[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=1)(CCCC)CCCC)CCC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN1CCCC1=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]>[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[CH2:39][C:40]3[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=3)=[CH:25][CH:24]=2)[CH:20]=[CH:21]1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 234424813-(Tributylstannanylmethyl)pyridineHCID 57807978(2E)-3-[2-Bromo-4-(trifluoromethyl)phenyl]-N-indol-5-ylprop-2-enamide

Product 1

HCID 57808273(2E)-N-Indol-5-yl-3-[2-(3-pyridylmethyl)-4-(trifluoromethyl)phenyl]prop-2-enamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2E)-3-[2-bromo-4-(trifluoromethyl)phenyl]-N-indol-5-ylprop-2-enamide, Example 97, (110 mg, 0.27 mmol), 3-(tributylstannanylmethyl)pyridine, Example 90(a), (160 mg, 0.43 mmol), tris(dibenzylideneacetone)dipalladium(0) (24 mg, 0.027 mmol, Aldrich) and triphenylphosphine (28 mg, 0.11 mmol, Aldrich) in 1-methyl-2-pyrrolidinone (1.5 mL) was stirred at 100° 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 organic extracts were washed with satd NaCl (100 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (gradient: 0-70% EtOAc in hexane) provided the title compound as an orange solid. MP 202-203° C. MS (ESI, neg. ion) m/z: 420 (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 organic 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: 0-70% EtOAc in hexane)

Sources & evidence

ORD record
ord-dbcb8e23617f494e8d856ada92e943eb
Source dataset
uspto-grants-2009_09
Patent number
US07582657B2

Reaction notes

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