Sodium Carbonate → N-(4'-Cyano-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide

HRID 1660949Notes

Reaction equation

HRID 1660949 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].[N:12]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][CH:19]=2)[N:14]([C:21]2[CH:26]=[CH:25][C:24]([CH2:27][C:28]([NH:30][C:31]3[CH:36]=[CH:35][C:34](I)=[C:33]([C:38]([F:41])([F:40])[F:39])[CH:32]=3)=[O:29])=[CH:23][CH:22]=2)[CH:13]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.CCOC(C)=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:34]2[C:33]([C:38]([F:39])([F:40])[F:41])=[CH:32][C:31]([NH:30][C:28](=[O:29])[CH2:27][C:24]3[CH:23]=[CH:22][C:21]([N:14]4[C:15]5=[N:16][CH:17]=[CH:18][CH:19]=[C:20]5[N:12]=[CH:13]4)=[CH:26][CH:25]=3)=[CH:36][CH:35]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 119935762-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-(4-iodo-3-trifluoromethyl-phenyl)-acetamide

Product 1

HCID 11993577N-(4'-Cyano-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-cyanophenylboronic acid (62 mg, 0.42 mmol, 2 equiv) in EtOH (0.2 mL) is added dropwise to a mixture of 2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-(4-iodo-3-trifluoromethyl-phenyl)-acetamide (Example 12) (110 mg, 0.21 mmol), PdCl2(dppf)2 (5 mg, 0.01 mmol, 0.03 equiv), Na2CO3 (2 M solution in H2O, 0.42 mL, 0.84 mmol, 4 equiv) in toluene (1 mL) at reflux. The reaction mixture is stirred at reflux for 1 h, allowed to cool to rt and diluted with EtOAc and H2O. The aqueous layer is separated and extracted twice with EtOAc. The combined organic phase is washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. Silica gel column chromatography purification (CH2Cl2/MeOH, 96:4) provides the title compound as a white solid: ES-MS: 495.9 [M-H]−; single peak at tR=4.68 min (System 1); Rf=0.15 (CH2Cl2/MeOH, 96:4).

Workup

  1. temperatureat reflux
  2. temperatureat reflux for 1 h
  3. customThe aqueous layer is separated
  4. extractionextracted twice with EtOAc
  5. washThe combined organic phase is washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customSilica gel column chromatography purification (CH2Cl2/MeOH, 96:4)

Sources & evidence

ORD record
ord-6168c1083e834184a75fc31f4925010e
Source dataset
uspto-grants-2011_10
Patent number
US08030311B2

Reaction notes

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