4-Methylmorpholine → N-Methoxy-N-methylpicolinamide

HRID 366775Notes

Reaction equation

HRID 366775 reaction equation
CO[CH2:3][NH2:4].[C:5]([O-])([O-])=[O:6].[K+].[K+].ClC1C=C(SC[C:20]2[C:21]([C:26]([OH:28])=O)=[N:22][CH:23]=[CH:24][CH:25]=2)C=CC=1.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C1COCC1.O.C1COCC1.O.CN(C=O)C>[CH3:5][O:6][N:4]([CH3:3])[C:26]([C:21]1[CH:20]=[CH:25][CH:24]=[CH:23][N:22]=1)=[O:28]

Participants

11

Reactant 6

HCID 79724-MethylmorpholineHCID 11430Potassium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 177781771-MethoxymethanamineHCID 23289862HCID 23289862, compound

Product 1

HCID 11829796N-Methoxy-N-methylpicolinamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

N-Methoxymethylamine (1.05 g) was dissolved in THF-water (25:1, 5 ml) with anhydrous K2CO3 (1.5 g), and the solution was stirred at room temperature for 30 minutes. It was then transferred by syringe into a flask containing 3-[(3-chlorophenyl)thiomethyl]-2-pyridinecarboxylic acid (2.0 g, 7.16 mmol) in a mixture of THF (3 ml), DMF (2 ml) and NMM (0.5 ml). HOBT (180 mg, 1.33 mmol) and EDCI (255 mg, 1.33 mmol) were added at 0° C. and the mixture was then stirred 28 hours at room temperature. The reaction mixture was diluted with water and extracted with EtOAc. The extracts were washed with brine, dried (Na2SO4), filtered and concentrated. The product was chromatographed on silica in 2%MeOH/CH2Cl2 and afforded 200 mg of 3-[(3-chlorophenyl)thiomethyl)]-N-methoxy-N-methyl-2-pyridinecarboxamide; MS (EI, M)=292; MS (CI, M+H)=293.

Workup

  1. customIt was then transferred by syringe into a flask
  2. stirringthe mixture was then stirred 28 hours at room temperature
  3. extractionextracted with EtOAc
  4. washThe extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was chromatographed on silica in 2%MeOH/CH2Cl2

Sources & evidence

ORD record
ord-29cd8fb7375d44b194f26d21dc79e6c2
Source dataset
uspto-grants-2000_10
Patent number
US06130229

Reaction notes

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