Methyl iodide → 8-chloro-9-methoxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398460Notes

Reaction equation

HRID 1398460 reaction equation
[Cl:1][C:2]1[C:3]([OH:19])=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1.[H-].[Na+].[CH3:22]I>CN(C=O)C.O>[Cl:1][C:2]1[C:3]([O:19][CH3:22])=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 867104338-chloro-9-hydroxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one

Product 1

HCID 867103738-chloro-9-methoxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 38.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To the stirred solution of 8-chloro-9-hydroxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (0.3 g, 1.092 mmol) in DMF (10 mL) cooled to 0° C., was added NaH (0.052 g, 2.184 mmol) followed by methyl iodide (0.205 mL, 3.28 mmol). The resultant mixture was allowed to stir at ambient temperature for 10 h. The reaction mixture was then diluted with water (50 mL) and extracted with ethyl acetate (2×80 mL). The combined organic layers were separated, washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using 70% ethyl acetate in petroleum ether to afford 8-chloro-9-methoxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (0.12 g, 0.416 mmol, 38% yield) as a semi-solid. LC/MS (ESI) m/e 288.4 [(M)+, calcd for C15H13ClN2O2 288.1]; LC/MS retention time (Method A): tR=1.9 min.

Workup

  1. extractionextracted with ethyl acetate (2×80 mL)
  2. customThe combined organic layers were separated
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b5f8d20e3ffc4430bf60d0870e2b632c
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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