Acetonitrile tetrahydrofuran → 5-bromo-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 886622Notes

Reaction equation

HRID 886622 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:5]2=[N:6][CH:7]=1.COOB([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)O.C1C[O:34][CH2:33]C1.C(#N)C>>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:34][CH3:33])=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 3

HCID 22177404Acetonitrile tetrahydrofuranHCID 53405446Methoxyphenyl boronic acidHCID 592970265-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 592970285-bromo-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridineYield 29%

Conditions

Temperature
50 °C

Procedure

A mixture of 5-bromo-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (8.0 g, 17.6 mmol), methoxyphenyl boronic acid (2.9 g, 19.4 mmol), dichloro[1,1′-bis(diphenyl-phosphino)ferrocene]palladium(II) dichloromethane adduct (646 mg, 0.9 mmol) in THF/Acetonitrile/saturated NaHCO3 (50 ml/50 ml/50 ml) was stirred at 50° C. overnight under nitrogen. The mixture was allowed to cool to room temperature and was extracted with ethyl acetate (3×). The combined organic layers were extracted with brine, dried with Na2SO4, decanted, and concentrated to dryness. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 5-bromo-3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (2.2 g, 29% yield). NMR (500 MHz, DMSO-d6) δ 0.11 (s, 9H), 1.05 (m, 2H), 3.76 (m, 2H), 3.01 (s, 3H), 5.87 (s, 2H), 7.26 (m, 1H), 7.35 (m, 1H), 7.54 (m, 1H), 7.72 (m, 1H), 8.17 (s, 1H), 8.38 (m, 1H), 8.59 (m, 1H). MS: m/z 434.1 (M+H+).

Workup

  1. temperatureto cool to room temperature
  2. extractionwas extracted with ethyl acetate (3×)
  3. extractionThe combined organic layers were extracted with brine
  4. dry with materialdried with Na2SO4
  5. customdecanted
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-dcccde6ff93044ad873cbeb4451a2d60
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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