Sodium Carbonate → 2-[3,5-bis(trifluoromethyl)phenyl]-N-(6'-chloro-4-methyl-3,4'-bipyridin-3'-yl)-N,2-dimethylpropanamide

HRID 2074841Notes

Reaction equation

HRID 2074841 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([C:13]([CH3:27])([CH3:26])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([Cl:25])=[CH:22][C:23]=2I)[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:30][C:31]1[CH:36]=[CH:35][N:34]=[CH:33][C:32]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([C:13]([CH3:27])([CH3:26])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([Cl:25])=[CH:22][C:23]=2[C:32]2[CH:33]=[N:34][CH:35]=[CH:36][C:31]=2[CH3:30])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27627114-Methylpyridine-3-Boronic Acid4×HCID 866241982-[3,5-bis(trifluoromethyl)phenyl]-N-(6-chloro-4-iodo-3-pyridinyl)-N,2-dimethylpropanamide

Product 1

HCID 592159032-[3,5-bis(trifluoromethyl)phenyl]-N-(6'-chloro-4-methyl-3,4'-bipyridin-3'-yl)-N,2-dimethylpropanamideYield 83%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

2-[3,5-bis(trifluoromethyl)phenyl]-N-(6-chloro-4-iodo-3-pyridinyl)-N,2-dimethylpropanamide (400 mg, 0.726 mmol), 4-methylpyridine-3 boronic acid (130 mg, 0.944 mmol), sodium carbonate (0.8 mL, 2M), tetrakistriphenylphosphine palladium (7.8 mg, 0.00726 mmol) was added in dioxane (4 mL) and stirred under argon before heating in the microwave at 110° C. for 30 minutes, added more 4-methylpyridine-3 boronic acid (67.5 mg, 0.49 mmol) and tetrakistriphenylphosphinepalladium (7.8 mg, 0.00726 mmol) and heated at 110° C. for 30 minutes. therefore added more 4-methylpyridine-3 boronic acid (51 mg, 037 mmol), tetrakistriphenylphosphinepalladium (7.8 mg, 0.00726 mmol) and heated under microwave conditions at 110° C. for 30 minutes, therefore added 4-methylpyridine-3 boronic acid (47 mg, 0.34 mmol), tetrakistriphenylphosphinepalladium (7.8 mg, 0.00726 mmol) and heated at 110° C. for 30 minutes. Residue partitioned between EtOAc and Brine. Aqueous layer was extracted with EtOAc ×3. Combined extracts were dried and solvent evaporated. Residue purified on a 12+M horizon column eluting with Pet Ether to 1:1 EtOAc: Pet Ether. Unable to isolate clean fractions. Sample sent to be purified by Mass Directed Auto-Prep (MDAP) chromatography, white solid didn't dissolve was found to be desired material. This was combined with product isolated from the MDAP to afford the title compound as a white solid in an 83% yield.

Workup

  1. temperatureheated at 110° C. for 30 minutes
  2. temperatureheated under microwave conditions at 110° C. for 30 minutes
  3. customResidue partitioned between EtOAc and Brine
  4. extractionAqueous layer was extracted with EtOAc ×3
  5. customCombined extracts were dried
  6. customsolvent evaporated
  7. customResidue purified on a 12+M horizon column
  8. washeluting with Pet Ether to 1:1 EtOAc
  9. customUnable to isolate clean fractions
  10. customto be purified by Mass Directed Auto-Prep (MDAP) chromatography, white solid didn't
  11. dissolutiondissolve
  12. customisolated from the MDAP

Sources & evidence

ORD record
ord-a8fc2d71c3794fcd9ff2cf967a786e8f
Source dataset
uspto-grants-2011_04
Patent number
US07919491B2

Reaction notes

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