Potassium Carbonate → 4-{3-Amino-1-[3-(2-fluoropyridin-3-yl)phenyl]-1H-isoindol-1-yl}benzonitrile

HRID 2264728Notes

Reaction equation

HRID 2264728 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[C:13](Br)[CH:12]=2)[N:3]=1.[F:26][C:27]1[C:32](B(O)O)=[CH:31][CH:30]=[CH:29][N:28]=1.C(=O)([O-])[O-].[K+].[K+].COC=COC>C(O)C.O>[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:32]3[C:27]([F:26])=[N:28][CH:29]=[CH:30][CH:31]=3)[CH:12]=2)[N:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 5223901,2-DimethoxyetheneHCID 27832702-Fluoropyridine-3-boronic acidHCID 248752754-[3-Amino-1-(3-bromophenyl)-1H-isoindol-1-yl]benzonitrile

Product 1

HCID 595962824-{3-Amino-1-[3-(2-fluoropyridin-3-yl)phenyl]-1H-isoindol-1-yl}benzonitrileYield 70%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

4-[3-Amino-1-(3-bromophenyl)-1H-isoindol-1-yl]benzonitrile (0.086 g, 0.22 mmol) (Example 50), (2-fluoropyridin-3-yl)boronic acid (0.047 g, 0.33 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride dichloromethane adduct (0.018 g, 0.022 mmol), potassium carbonate (0.091 g, 0.66 mmol) and solvent (3 mL of a mixture of dimethoxyethene, water and ethanol in a ratio of 6:3:1) was irradiated under argon atmosphere in a microwave at 125° C. for 6 min. When cooled to ambient temperature the mixture was partitioned between ethyl acetate and water; the organic phase was dried over magnesium sulfate and evaporated. Purification by preparative HPLC to give 0.062 g (70% yield) of the title compound. 1H NMR (DMSO-d6) δ 8.22 (dd, J=3.28, 1.52 Hz, 1 H), 8.05-7.94 (m, 1 H), 7.84-7.75 (m, 2 H), 7.75-7.69 (m, 2 H), 7.56-7.34 (m, 9 H), 6.90 (br s, 2 H); MS (AP) m/z 405 [M+1]+.

Workup

  1. customwas partitioned between ethyl acetate and water
  2. dry with materialthe organic phase was dried over magnesium sulfate
  3. customevaporated
  4. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-95b8f3946032430db5e8d13c85801deb
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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