Acetone → N-(2-Methylpropyl)-3-nitro-1,5-naphthyridin-4-amine

HRID 1168360Notes

Reaction equation

HRID 1168360 reaction equation
P(Cl)(Cl)(Cl)=O.[N+:6]([C:9]1[CH:10]=[N:11][C:12]2[C:17]([C:18]=1O)=[N:16][CH:15]=[CH:14][CH:13]=2)([O-:8])=[O:7].CC(C)=O.[CH2:24]([NH2:28])[CH:25]([CH3:27])[CH3:26]>CN(C)C=O>[CH3:26][CH:25]([CH3:27])[CH2:24][NH:28][C:18]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][N:16]=2)[N:11]=[CH:10][C:9]=1[N+:6]([O-:8])=[O:7]

Participants

6

Reactant 4

HCID 180AcetoneHCID 6558IsobutylamineHCID 24813Phosphorus oxychlorideHCID 178526774HCID 178526774, compound

Product 1

HCID 54184816N-(2-Methylpropyl)-3-nitro-1,5-naphthyridin-4-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Phosphorous oxychloride (0.6 mL, 6.44 mmol) was reacted with N,N-dimethylformamide then added to a solution of 3-nitro[1,5]naphthyridin-4-ol (1.0 g, 5.23 mmol) in N,N-dimethylformamide (20 mL). The reaction mixture was warmed using a jacketed flask with refluxing acetone as a heat source. After 3 hours the reaction mixture was poured into ice water, isobutylamine (2.0 mL, 20.1 mmol) was added and the mixture was heated on a steam bath. After several hours the reaction mixture was cooled to ambient temperature, filtered and washed with water. The aqueous layer was extracted with dichloromethane. The dichloromethane extract was washed with aqueous sodium bicarbonate, washed with water, dried over magnesium filtrate then loaded onto a layer of silica gel. The silica gel was eluted initially with dichloromethane to remove an impurity then with 5% methanol in dichloromethane to recover the product. The eluant was concentrated to dryness to provide N4-(2-methylpropyl)-3-nitro(1,5]naphthyridin-4-amine as a solid, m.p. 97-99° C.

Workup

  1. temperatureThe reaction mixture was warmed
  2. additionwas added
  3. temperaturethe mixture was heated on a steam bath
  4. filtrationfiltered
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. extractionThe dichloromethane extract
  8. washwas washed with aqueous sodium bicarbonate
  9. washwashed with water
  10. dry with materialdried over magnesium filtrate
  11. washThe silica gel was eluted initially with dichloromethane
  12. customto remove an impurity
  13. customwith 5% methanol in dichloromethane to recover the product
  14. concentrationThe eluant was concentrated to dryness

Sources & evidence

ORD record
ord-14f12c191b254ed6b2000be14a7eeafe
Source dataset
uspto-grants-2003_09
Patent number
US06624172B2

Reaction notes

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