Sodium Hydroxide → 3-Chloro-6-methoxy-[1,5]naphthyridine-4-carboxylic acid amide

HRID 1422971Notes

Reaction equation

HRID 1422971 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[C:12]#[N:13])=[N:9][C:8]([O:14][CH3:15])=[CH:7][CH:6]=2.[OH-:16].[Na+]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[C:12]([NH2:13])=[O:16])=[N:9][C:8]([O:14][CH3:15])=[CH:7][CH:6]=2

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 672545843-Chloro-6-methoxy-[1,5]naphthyridine-4-carbonitrile

Product 1

HCID 672571323-Chloro-6-methoxy-[1,5]naphthyridine-4-carboxylic acid amideYield 64%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3-Chloro-6-methoxy-[1,5]naphthyridine-4-carbonitrile (5.0 g, 22.8 mmol, 1.0 eq) is suspended in a 10% sodium hydroxide aqueous solution (125 mL) and the resulting mixture is heated to reflux for 30 minutes. The reaction mixture is then extracted with ethyl acetate (3×100 mL) and the pH is adjusted to 3-4 by the addition of a 3N hydrochloric acid aqueous solution. The combined organic layers are dried over sodium sulfate, filtered and concentrated to give the crude product that is purified by column chromatography (silica gel, eluent: ethyl acetate:petroleum ether, 1:1 to 4:1, v/v) to afford 3-chloro-6-methoxy-[1,5]naphthyridine-4-carboxylic acid amide as an off-white solid (3.44 g, 64% yield).

Workup

  1. temperaturethe resulting mixture is heated
  2. temperatureto reflux for 30 minutes
  3. extractionThe reaction mixture is then extracted with ethyl acetate (3×100 mL)
  4. additionthe pH is adjusted to 3-4 by the addition of a 3N hydrochloric acid aqueous solution
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product that
  9. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-003dbd83e09141a9b6f2eb4c31049521
Source dataset
uspto-grants-2015_01
Patent number
US08927541B2

Reaction notes

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