Potassium Carbonate → N-(3,5-Bis-trifluoromethyl-benzyl)-6-(3-cyano-phenoxy)-N-methyl-4-o-tolyl-nicotinamide

HRID 1835369Notes

Reaction equation

HRID 1835369 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]([CH3:24])[C:8](=[O:23])[C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][C:12](I)=[N:11][CH:10]=1.[OH:34][C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][CH:42]=1)[C:38]#[N:39].C(=O)([O-])[O-].[K+].[K+].COC(C)(C)C>N1C=CC=CC=1.[Cu-]=O>[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]([CH3:24])[C:8](=[O:23])[C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][C:12]([O:34][C:35]2[CH:42]=[CH:41][CH:40]=[C:37]([C:38]#[N:39])[CH:36]=2)=[N:11][CH:10]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 133943-CyanophenolHCID 15413tert-Butyl methyl etherHCID 10231844N-(3,5-Bis-trifluoromethyl-benzyl)-6-iodo-N-methyl-4-o-tolyl-nicotinamide

Product 1

HCID 23502813N-(3,5-Bis-trifluoromethyl-benzyl)-6-(3-cyano-phenoxy)-N-methyl-4-o-tolyl-nicotinamideYield 88.3%

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 1049PyridineSolvent

Procedure

A solution of 200 mg (0.346 mmol) N-(3,5-bis-trifluoromethyl-benzyl)-6-iodo-N-methyl-4-o-tolyl-nicotinamide (Example 4) and 84 mg (0.69 mmol) 3-hydroxybenzonitrile in 4 ml pyridine was deoxygenated by three freeze-thaw cycles. After addition of 5 mg (0.04 mmol) copper(I) oxide and 96 mg (0.69 mmol) potassium carbonate under a stream of argon the reaction mixture was heated at reflux for 70 h. Cooling to room temperature was followed by dilution with tert-butyl methyl ether and washing with two portions of 1 M aqueous hydrochloric acid solution. The combined aqueous layers were extracted with tert-butyl methyl ether. The combined organic layers were washed with saturated aqueous sodium carbonate solution and brine, dried with sodium sulfate and concentrated. Column chromatography afforded 174 mg (88%) of the title compound as a light brown solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 70 h
  3. washwashing with two portions of 1 M aqueous hydrochloric acid solution
  4. extractionThe combined aqueous layers were extracted with tert-butyl methyl ether
  5. washThe combined organic layers were washed with saturated aqueous sodium carbonate solution and brine
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-7ffcc908951e4c7f998cda365d29fe6c
Source dataset
uspto-grants-2004_08
Patent number
US06770637B2

Reaction notes

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