Oxalyl chloride → N-{3-[(6-aminopyridin-3-yl)oxy]phenyl}-3-methylpyridine-2-carboxamide

HRID 1874385

Reaction equation

HRID 1874385 reaction equation
[CH3:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[NH2:17][C:18]1[CH:19]=[C:20]([CH:29]=[CH:30][CH:31]=1)[O:21][C:22]1[CH:23]=[CH:24][C:25]([NH2:28])=[N:26][CH:27]=1>O1CCCC1.CN(C)C=O.CN(C)C(=O)C.C(=O)([O-])O.[Na+]>[NH2:28][C:25]1[N:26]=[CH:27][C:22]([O:21][C:20]2[CH:19]=[C:18]([NH:17][C:8]([C:3]3[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=3)=[O:10])[CH:31]=[CH:30][CH:29]=2)=[CH:23][CH:24]=1

Participants

8

Reactant 3

HCID 65578Oxalyl chlorideHCID 2687573-Methylpicolinic acidHCID 577491665-(3-Aminophenoxy)pyridin-2-amine

Product 1

HCID 57749261N-{3-[(6-aminopyridin-3-yl)oxy]phenyl}-3-methylpyridine-2-carboxamideYield 63.2%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 3-methylpyridine-2-carboxylic acid (1.38 g, 10.1 mmol) in tetrahydrofuran (100 mL) were added N,N-dimethylformamide (2 drops) and oxalyl chloride (1.75 mL, 20.2 mmol) at 0° C., and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylacetamide (50 mL). A solution of 5-(3-aminophenoxy)pyridin-2-amine (1.83 g, 9.09 mmol) in N,N-dimethylacetamide (5 mL) was added with stirring at room temperature, and the mixture was stirred at room temperature for 13 hr. The reaction mixture was diluted with aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure and washed with ethyl acetate-hexane to give the title compound (1.84 g, 57%) as a pale-brown solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (50 mL)
  3. stirringwith stirring at room temperature
  4. stirringthe mixture was stirred at room temperature for 13 hr
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltrated
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. washwashed with ethyl acetate-hexane

Sources & evidence

ORD record
ord-5f31dea26b6c470b9cce8a08a33e9808
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Linked notes

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