Acetic Acid → 2-Amino-7-chloro-N-methyl-4-oxo-1-(pyridin-2-ylmethyl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide

HRID 1260583Notes

Reaction equation

HRID 1260583 reaction equation
[H-].[Na+].[CH3:3][NH:4][C:5](=[O:9])[CH2:6][C:7]#[N:8].[Cl:10][C:11]1[CH:19]=[CH:18][C:14]([C:15](F)=[O:16])=[C:13]([NH:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[N:12]=1.C(O)(=O)C>CN(C)C=O>[NH2:8][C:7]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[C:13]2[C:14]([C:15](=[O:16])[C:6]=1[C:5]([NH:4][CH3:3])=[O:9])=[CH:18][CH:19]=[C:11]([Cl:10])[N:12]=2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydride2×HCID 806222-Cyano-N-methylacetamideHCID 866423376-Chloro-2-[(pyridin-2-ylmethyl)amino]nicotinoyl fluoride

Product 1

HCID 866423382-Amino-7-chloro-N-methyl-4-oxo-1-(pyridin-2-ylmethyl)-1,4-dihydro-1,8-naphthyridine-3-carboxamideYield 234.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

1.12 g (28.06 mmol) of sodium hydride at 60% in mineral oil are added, fractionwise, to a solution, cooled to 0-5° C., of 1.31 g (13.36 mmol) of N-methylcyanoacetamide (prepared according to 1.3) in 20 ml of anhydrous dimethylformamide. Stirring is continued at this temperature for ten minutes and then a solution of 3.55 g (4.93 mmol) of 6-chloro-2-[(pyridin-2-ylmethyl)amino]nicotinoyl fluoride in 20 ml of dimethylformamide is added. The medium is stirred overnight at ambient temperature and then 0.561 g (14.03 mmol) of sodium hydride at 60% is added fractionwise. Stirring is continued at this temperature for 1 hour minutes, and then the reaction mixture is poured onto ice and the subsequent mixture is acidified to pH 5-6 with an aqueous solution of acetic acid at 10%. The precipitate is isolated by filtration and, after drying in an oven, 3.98 g of the expected product are obtained in the form of a beige solid. MH+=344. Yield=87%.

Workup

  1. waitis continued at this temperature for ten minutes
  2. stirringThe medium is stirred overnight at ambient temperature
  3. stirringStirring
  4. additionthe reaction mixture is poured onto ice
  5. customThe precipitate is isolated by filtration
  6. customafter drying in an oven

Sources & evidence

ORD record
ord-4eed82a767c34567aa03e284df4a0a94
Source dataset
uspto-grants-2013_06
Patent number
US08470847B2

Reaction notes

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