4-Vinylpyridine → (E)-3-(2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carbaldehyde

HRID 1615350Notes

Reaction equation

HRID 1615350 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]=[O:12])[CH:9]=2)[N:4]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:3]=1.CC([O-])=O.[Na+].[CH:26]([C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)=[CH2:27].C(OCC)(=O)C>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[N:31]1[CH:32]=[CH:33][C:28](/[CH:26]=[CH:27]/[C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([CH:11]=[O:12])[CH:9]=3)[N:4]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:3]=2)=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 75024-VinylpyridineHCID 8857Ethyl AcetateHCID 517045Sodium AcetateHCID 584075833-Iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-indazole-5-carbaldehyde

Product 1

HCID 86651988(E)-3-(2-(pyridin-4-yl)vinyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carbaldehydeYield 52%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-5-carbaldehyde (87 mg, 0.22 mmol), NaOAc (36 mg, 0.44 mmol), nBu4NCl (61 mg, 0.44 mmol), and Pd(OAc)2 (8.0 mg, 0.036 mmol) in DMF (2 mL) under argon was added 4-vinylpyridine (0.05 mL, 0.46 mmol). The resulting mixture was heated in a sealed vial at 100° C. for 14 hours. Ethyl acetate (200 mL) was added and the solution was washed with water (20 mL) and brine (3×20 mL), dried over Na2SO4 and concentrated. The residue was chromatographed (5 g silica SPE tube, Silicycle, 1-2% MeOH in CH2Cl2, repeated for mixed fractions) gave the title compound as a yellow solid (43 mg, 52%). 1H NMR (400 MHz, CDCl3 plus a drop of CD3OD) δ 10.07 (s, 1H), 8.52 (m, 3H), 7.97 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.8 Hz, 1H); 7.60 (d, J=16.4 Hz, 1H); 7.48 (m, 3H); 5.73 (s, 2H), 3.56 (m, 2H), 0.86 (m, 2H), −0.12 (s, 9H).

Workup

  1. washthe solution was washed with water (20 mL) and brine (3×20 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was chromatographed
  5. addition(5 g silica SPE tube, Silicycle, 1-2% MeOH in CH2Cl2, repeated for mixed fractions)

Sources & evidence

ORD record
ord-0a7dc524715a4cf6a3bab53f802f40da
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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