Phenylboronic Acid → 2-acetamido-N-((5-phenyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)isonicotinamide

HRID 623660Notes

Reaction equation

HRID 623660 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:25]=[CH:26][N:27]=1)[C:8]([NH:10][CH2:11][C:12]1[CH:13]=[N:14][C:15]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[C:16](Br)[CH:17]=1)=[O:9])(=[O:3])[CH3:2].[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])O.[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>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:25]=[CH:26][N:27]=1)[C:8]([NH:10][CH2:11][C:12]1[CH:13]=[N:14][C:15]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[C:16]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:17]=1)=[O:9])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 675096872-acetamido-N-((5-bromo-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)isonicotinamide

Product 1

HCID 675083942-acetamido-N-((5-phenyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)isonicotinamideYield 30%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-acetamido-N-((5-bromo-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)isonicotinamide (20 mg, 0.05 mmol, Step-1), phenylboronic acid (11 mg, 0.09 mmol), tetrakis(triphenylphosphine)palladium (3 mg, 2.2 microM) in dioxane (2 mL) is added saturated aqueous sodium hydrogencarbonate (0.4 mL). The mixture is heated at 100° C. for 1 hr. After cooled to room temperature, the mixture is extracted with ethyl acetate, dried over sodium sulfate. The organic solvent is removed under reduced pressure. The residue is purified by short column chromatography on amine gel eluting with ethylacetate, and then purified by preparative LC-MS to give 6 mg (30% yield) of the title compound.

Workup

  1. temperatureAfter cooled to room temperature
  2. extractionthe mixture is extracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. customThe organic solvent is removed under reduced pressure
  5. customThe residue is purified by short column chromatography on amine gel
  6. washeluting with ethylacetate
  7. custompurified by preparative LC-MS

Sources & evidence

ORD record
ord-e3a7e2a9a0f6446e9be6940130e82e8f
Source dataset
uspto-grants-2016_04
Patent number
US09302991B2

Reaction notes

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