Water → HCID 18467081, compound

HRID 2229396Notes

Reaction equation

HRID 2229396 reaction equation
[NH2:1][C:2]1[C:3](=[O:24])[N:4]([CH2:20][CH2:21][CH2:22][CH3:23])[C:5]2[C:10]([C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)=[CH:9][CH:8]=[CH:7][N:6]=2.[C:25](Cl)(=O)[O:26]C1C=CC=CC=1.O.[CH:36]([C:39]1[CH:45]=[C:44]([O:46]C(=O)C2C=CC=C(Cl)C=2)[CH:43]=[C:42]([CH:56]([CH3:58])[CH3:57])[C:40]=1[NH2:41])([CH3:38])[CH3:37]>O1CCCC1.CN(C)C=O.CN(C)C1C=CN=CC=1>[CH2:20]([N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][N:6]=2)[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)=[C:2]([NH:1][C:25]([NH:41][C:40]2[C:42]([CH:56]([CH3:57])[CH3:58])=[CH:43][C:44]([OH:46])=[CH:45][C:39]=2[CH:36]([CH3:37])[CH3:38])=[O:26])[C:3]1=[O:24])[CH2:21][CH2:22][CH3:23]

Participants

8

Reactant 4

HCID 962Water2×HCID 15891Phenyl chloroformateHCID 11232543HCID 11232543, compoundHCID 18467080HCID 18467080, compound

Product 1

HCID 18467081HCID 18467081, compoundYield 55.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 3-amino-1-butyl-4-(3-methoxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridine (2.14 g, 6.63 mmol) in tetrahydrofuran (20 ml) is added phenyl chlorocarbonate (1.66 ml, 13.2 mmol), and the mixture is stirred at 40-50° C. for 3 hours. After allowed to cool, water is added to the mixture, and the mixture is extracted with ethyl acetate. The extract is washed with a 5% aqueous brine, and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue is dissolved in dimethylformamide (30 ml), and thereto are added dropwise successively a solution of 2,6-diisopropyl-4-(3-chlorobenzoyloxy)aniline (2.0 g, 6.03 mmol) in dimethylformamide (5 ml), and a solution of 4-dimethylaminopyridine (0.74 g, 12 mmol) in dimethylformamide (5 ml) at room temperature. The mixture is stirred at room temperature for 8 hours, and to the reaction solution is added water. The mixture is extracted with ethyl acetate. The extract is washed successively with an aqueous ammonium chloride solution, an aqueous sodium hydrogen carbonate solution, and a saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (ethyl acetate:hexane=1:5→ethyl acetate:hexane=1:2) to give the title compound (2.1 g, 3.35 mmol) as amorphous.

Workup

  1. temperatureto cool
  2. extractionthe mixture is extracted with ethyl acetate
  3. washThe extract is washed with a 5% aqueous brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting residue is dissolved in dimethylformamide (30 ml)
  7. customat room temperature
  8. stirringThe mixture is stirred at room temperature for 8 hours
  9. extractionThe mixture is extracted with ethyl acetate
  10. washThe extract is washed successively with an aqueous ammonium chloride solution
  11. dry with materialan aqueous sodium hydrogen carbonate solution, and a saturated brine, dried over anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe resulting residue is purified by silica gel column chromatography (ethyl acetate:hexane=1:5→ethyl acetate:hexane=1:2)

Sources & evidence

ORD record
ord-7cbbf3c579734560a230d18412c8ee38
Source dataset
uspto-grants-2002_07
Patent number
US06420381B1

Reaction notes

Loading…