5-Bromo-2-methoxypyridine → 6-(2-methoxypyridin-5-yl)-3-((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole

HRID 1861114Notes

Reaction equation

HRID 1861114 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C[Sn](C)C.C[Sn](C)C.I[C:19]1[CH:27]=[C:26]2[C:22]([C:23](/[CH:36]=[CH:37]/[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[N:24][N:25]2[CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])=[CH:21][CH:20]=1>O1CCOCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][O:8][C:5]1[CH:4]=[CH:3][C:2]([C:19]2[CH:27]=[C:26]3[C:22]([C:23](/[CH:36]=[CH:37]/[C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)=[N:24][N:25]3[CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:33])([CH3:34])[CH3:35])=[CH:21][CH:20]=2)=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 27348955-Bromo-2-methoxypyridineHCID 6327618HexamethylditinHCID 218772551H-Indazole, 6-iodo-3-[(1E)-2-phenylethenyl]-1-[[2-(trimethylsilyl)ethoxy]methyl]-

Product 1

HCID 218774306-(2-methoxypyridin-5-yl)-3-((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazoleYield 40.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-bromo-2-methoxypyridine (2.00 g, 6.10 mmol), hexamethylditin (1.15 g, 6.10 mmol), and Pd(PPh3)4 (0.28 g, 0.24 mmol) in degassed dioxane (10 ml ) was refluxed under for 16 h. 6-Iodo-3-((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole (2.90 g, 6.10 mmol) was added to above mixture, followed by Pd(PPh3)4 (0.35 g 0.31 mmol ). The reaction mixture was refluxed for 16 h. The mixture was then diluted with ethyl acetate (150ml), and washed with brine (30 ml). The organics were dried over MgSO4, then concentrated under reduced pressure. Purification by silica gel chromatography gave 6-(2-methoxypyridin-5-yl)-3-((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole as a yellow solid (1.12 g, 40%). 1H NMR (300 MHz, CDCl3) δ 8.51 (d, 1H, J=2.5 Hz), 8.50 (d, 1H, J=9.1 Hz), 7.93 (dd, 1H, J=2.5, 8.6 Hz), 7.69 (s, 1H), 7.69-7.28 (m, 8H), 6.89 (d, 1H, J=8.6 Hz), 5.83 (s, 2H), 4.03 (s, 3H), 3.64 (t, 2H, J=8.3 Hz), 0.93 (t, 2H, J=8.3 Hz), −0.03 (s, 9H).

Workup

  1. temperatureThe reaction mixture was refluxed for 16 h
  2. washwashed with brine (30 ml)
  3. dry with materialThe organics were dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-0f44802e047642088e32ac2d8126bb13
Source dataset
uspto-grants-2003_03
Patent number
US06531491B1

Reaction notes

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