2-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride) → 5-bromo-3-(2-trifluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine

HRID 1865696Notes

Reaction equation

HRID 1865696 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[N: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.[F:20][C:21]([F:33])([F:32])[O:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O>C1COCC1.C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[O:22][C:21]([F:20])([F:33])[F:32])=[N: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 2

HCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 598361345-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 579758215-bromo-3-(2-trifluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridineYield 59%

Reagents, catalysts & solvents 1

HCID 22177404Acetonitrile tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 5-bromo-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (3.5 g, 7.7 mmol), 2-trifluoromethoxyphenylboronic acid (2.2 g, 7.7 mmol), dichloro[1,1′bis(diphenyl-phosphino) ferrocene]palladium(II) dichloromethane adduct (284 mg, 0.4 mmol) in THF/Acetonitrile/saturated NaHCO3 (25 ml/25 ml/30 ml) was stirred at 60° C. for 4 hours. The mixture was allowed to cool down to room temperature and then extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over Na2SO4, decanted, and concentrated to dryness. Silica chromatography of the crude using a gradient of ethyl acetate and hexane afforded 5-bromo-3-(2-trifluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (2.2 g, 59% yield). 1H NMR (500 MHz, DMSO-d6) δ 0.02 (s, 9H), 0.94 (m, 2H), 3.77 (m, 2H), 6.00 (s, 2H), 7.75 (m, 2H), 7.80 (d, 1H), 8.01 (d, 1H), 8.66 (s, 1H), 8.91 (s, 1H). MS: m/z 489.1 (M+H+).

Workup

  1. temperatureto cool down to room temperature
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. customdecanted
  6. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-cb9a2396dcd445e4a8310620a6b06842
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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