Nitrogen → (E)-Ethyl 3-(4-((E)-2-phenyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate

HRID 2069583Notes

Reaction equation

HRID 2069583 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][O:15]1)[N:9]=[CH:8]2)#[C:2][CH2:3][CH3:4].I[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH2:27]([O:29][C:30](=[O:42])/[CH:31]=[CH:32]/[C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)[CH3:28].C([O-])([O-])=O.[K+].[K+].N#N>CN(C)C=O.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.CN(C)C=O.O>[C:21]1(/[C:2](/[CH2:3][CH3:4])=[C:1](\[C:36]2[CH:37]=[CH:38][C:33](/[CH:32]=[CH:31]/[C:30]([O:29][CH2:27][CH3:28])=[O:42])=[CH:34][CH:35]=2)/[C:5]2[CH:6]=[C:7]3[C:11](=[CH:12][CH:13]=2)[N:10]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[N:9]=[CH:8]3)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 11575IodobenzeneHCID 59425074-(E-3-Ethoxy-3-oxo-1-propen-1-yl)benzeneboronic acidHCID 667932705-(But-1-yn-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole2×

Product 1

HCID 66794674(E)-Ethyl 3-(4-((E)-2-phenyl-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate

Reagents, catalysts & solvents 3

HCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 6228DimethylformamideSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
45 °C

Procedure

A solution of 5-(but-1-yn-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (2.5 g, 9.83 mmol, Intermediate 3), iodobenzene (6 g, 29.5 mmol), (E)-(4-(3-ethoxy-3-oxoprop-1-en-1-yl)phenyl)boronic acid (6.49 g, 29.5 mmol), K2CO3 (4.08 g, 29.5 mmol), and N,N-dimethylformamide/water (2:1, 492 mL) was degassed with 3 vacuum/N2 cycles and then heated at 45° C. until it was a homogenous solution. A solution of Pd(PhCN)2Cl2 (38 mg, 0.098 mmol) in N,N-dimethylformamide (0.5 mL) was added. The resulting mixture was stirred at 45° C. overnight. Upon completion, the reaction mixture was cooled down to room temperature, quenched with water (500 mL), and extracted with ethyl acetate (3×500 mL). The combined organics were washed with water, washed with brine, dried over sodium sulfate, filtered, and concentrated to give the crude product. This crude material was purified on a silica gel column eluted with 0-50% ethyl acetate in hexanes affording the title compound as off-white foam (3.71 g). LCMS: 423 [(M-THP+H)+H]+.

Workup

  1. temperatureUpon completion, the reaction mixture was cooled down to room temperature
  2. customquenched with water (500 mL)
  3. extractionextracted with ethyl acetate (3×500 mL)
  4. washThe combined organics were washed with water
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6d5beccffe5440dfbe7b850128f43d4d
Source dataset
uspto-grants-2012_10
Patent number
US08299112B2

Reaction notes

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