Dichloromethane → 3-(6-Aminopyridin-2-yl)-4-methyl-N-[3-(trifloromethyl)phenyl]benzamide

HRID 1894900Notes

Reaction equation

HRID 1894900 reaction equation
I[C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[CH3:21])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=1)=[O:6].C([O-])(=O)C.[K+].CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C(Cl)Cl.C(=O)([O-])[O-].[K+].[K+].Br[C:55]1[N:60]=[C:59]([NH2:61])[CH:58]=[CH:57][CH:56]=1>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].O.CN(C=O)C>[NH2:61][C:59]1[N:60]=[C:55]([C:2]2[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=2[CH3:21])[C:5]([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)=[O:6])[CH:56]=[CH:57][CH:58]=1

Participants

10

Reactant 6

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 3008092-Amino-6-bromopyridineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 171975693-iodo-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide

Product 1

HCID 690476313-(6-Aminopyridin-2-yl)-4-methyl-N-[3-(trifloromethyl)phenyl]benzamide

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a degassed mixture of 3-iodo-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide (0.500 g, 1.23 mmol), potassium acetate (424 mg, 4.32 mmol), DMF (15 mL), and 4,4,5,5,4′,4′,5′,5′-octamethyl-[2,2′]bi[[1,3,2]dioxaborolanyl] (0.329 g, 1.30 mmol) was added [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with DCM (1:1) (101 mg, 0.123 mmol). The reaction was heated to 80° C. for 3 hours, at which time conversion to the boronic ester was complete. The mixture was cooled and potassium carbonate (512 mg, 3.70 mmol), water (2.24 mL), and 6-bromopyridin-2-amine (214 mg, 1.23 mmol) were added. After degassing the mixture, it was heated to 85° C. for 1 hour. The solvent was then removed in vacuo. Water was added and the product was extracted with three portions of ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, and concentrated. Purification was carried out by flash column chromatography (eluting with a gradient from 0-50% ethyl acetate in hexanes) afforded the product. (254 mg, 50%).

Workup

  1. temperatureThe mixture was cooled
  2. customAfter degassing the mixture, it
  3. customThe solvent was then removed in vacuo
  4. additionWater was added
  5. extractionthe product was extracted with three portions of ethyl acetate
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customPurification
  10. washeluting with a gradient from 0-50% ethyl acetate in hexanes)
  11. customafforded the product

Sources & evidence

ORD record
ord-e68678bbf3e54894a4d9209b2579f97e
Source dataset
uspto-grants-2013_08
Patent number
US08513270B2

Reaction notes

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