Sodium Carbonate → 2'-Methyl-4-o-tolyl-[2,4']bipyridinyl-5-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amide

HRID 1835346Notes

Reaction equation

HRID 1835346 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[Na+].[Na+].[F:38][C:39]([F:70])([F:69])[C:40]1[CH:41]=[C:42]([CH:62]=[C:63]([C:65]([F:68])([F:67])[F:66])[CH:64]=1)[CH2:43][N:44]([CH3:61])[C:45](=[O:60])[C:46]1[C:51]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[CH3:58])=[CH:50][C:49](I)=[N:48][CH:47]=1>CN(C)C=O.C(=O)(O)[O-].[Na+].[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.Cl[Pd]Cl.[Fe+2]>[F:38][C:39]([F:70])([F:69])[C:40]1[CH:41]=[C:42]([CH:62]=[C:63]([C:65]([F:68])([F:67])[F:66])[CH:64]=1)[CH2:43][N:44]([CH3:61])[C:45]([C:46]1[C:51]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[CH3:58])=[CH:50][C:49]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=2)=[N:48][CH:47]=1)=[O:60]

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 10231844N-(3,5-Bis-trifluoromethyl-benzyl)-6-iodo-N-methyl-4-o-tolyl-nicotinamideHCID 126913224-Iodo-2-methylpyridine

Product 1

HCID 101197802'-Methyl-4-o-tolyl-[2,4']bipyridinyl-5-carboxylic acid (3,5-bis-trifluoromethyl-benzyl)-methyl-amideYield 78.4%

Reagents, catalysts & solvents 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 300 mg (1.37 mmol) 4-iodo-2-methyl-pyridine, 383 mg (1.51 mmol) bis(pinacolato)diboron and 403 mg (4.11 mmol) potassium acetate in 8.5 ml N,N-dimethylformamide was deoxygenated by three freeze-thaw cycles. After addition of 112 mg (0.137 mmol) dichloro(1,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloromethane adduct the reaction mixture was stirred at 80° C. for 3 h. Cooling to room temperature was followed by addition of 4 ml of a 2 M aqueous solution of sodium carbonate, 396 mg (0.685 mmol) N-(3,5-bis-trifluoromethyl-benzyl)-6-iodo-N-methyl-4-o-tolyl-nicotinamide (Example 4) and 56 mg (0.068 mmol) dichloro(1,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloromethane adduct. The reaction mixture was reheated to 80° C. for 1.5 h. After cooling to room temperature the reaction mixture was diluted with aqueous sodium bicarbonate solution and extracted with three portions of ethyl acetate. The combined organic extracts were dried with sodium sulfate, filtered and concentrated. Drying in high vacuo at 50° C. and flash column chromatography gave 292 mg (78%) of the title compound as a light brown solid.

Workup

  1. customwas deoxygenated by three freeze-thaw cycles
  2. temperatureCooling to room temperature
  3. waitThe reaction mixture was reheated to 80° C. for 1.5 h
  4. temperatureAfter cooling to room temperature the reaction mixture
  5. extractionextracted with three portions of ethyl acetate
  6. dry with materialThe combined organic extracts were dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customDrying in high vacuo at 50° C.

Sources & evidence

ORD record
ord-6821f57ef0254fb1aa7715f82503cf55
Source dataset
uspto-grants-2004_08
Patent number
US06770637B2

Reaction notes

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