1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2,6-difluoro-N-methoxy-N-methylnicotinamide

HRID 1436097Notes

Reaction equation

HRID 1436097 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[F:27][C:28]1[N:36]=[C:35]([F:37])[CH:34]=[CH:33][C:29]=1[C:30](O)=[O:31].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C.O>[F:27][C:28]1[N:36]=[C:35]([F:37])[CH:34]=[CH:33][C:29]=1[C:30]([N:3]([O:4][CH3:5])[CH3:2])=[O:31]

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 105830702,6-Difluoropyridine-3-carboxylic acid

Product 1

HCID 866126072,6-difluoro-N-methoxy-N-methylnicotinamideYield 91.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N,O-dimethylhydroxylamine hydrochloride (14.7 g), WSC (28.9 g), and HOBt (20.4 g) were added to a solution of 2,6-difluoronicotinic acid (6 g) and diisopropylethylamine (10 mL) in DMF (100 mL), and the reaction solution was stirred at room temperature for two days. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: ethyl acetate) to obtain 7.01 g of the title compound.

Workup

  1. customthe organic layer was separated
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: ethyl acetate)

Sources & evidence

ORD record
ord-5c24331af79644568f706ec44563e5fe
Source dataset
uspto-grants-2009_11
Patent number
US07618960B2

Reaction notes

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