Propanedioyl dichloride → 5-(3-Cyanophenyl)-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione

HRID 1260274Notes

Reaction equation

HRID 1260274 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[NH:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[C:16]#[N:17].[C:21](Cl)(=[O:26])[CH2:22][C:23](Cl)=[O:24].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[C:16]([C:15]1[CH:14]=[C:13]([N:12]2[C:23](=[O:24])[CH2:22][C:21](=[O:26])[NH:1][C:2]3[C:11]4[C:6]([CH:5]=[CH:4][C:3]2=3)=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH:20]=[CH:19][CH:18]=1)#[N:17]

Participants

5

Reactant 3

HCID 74269Propanedioyl dichlorideHCID 516892Sodium BicarbonateHCID 679939123-(1-Amino-2-naphthylamino)benzonitrile

Product 1

HCID 468632195-(3-Cyanophenyl)-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dioneYield 27.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To an ice-cold solution of 3-(1-amino-2-naphthylamino)benzonitrile (968 mg, 3.73 mmol) in toluene (10 mL) was added malonyl chloride (436 μL, 4.48 mmol). The mixture was stirred at 80° C. for 20 minutes, then at 110° C. for 10 minutes. After the reaction mixture was cooled to room temperature, the solution part of the reaction mixture was poured into a saturated aqueous sodium bicarbonate solution, and was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. While The precipitated solid in the reaction mixture was dissolved in chloroform, was washed with a saturated aqueous sodium bicarbonate solution, and saturated brine. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The residues were combined, and Each product purified by silica gel column chromatography (hexane/ethyl acetate=1/4), and the residue was recrystallized from ethyl acetate to give the titled compound as a pale yellow crystal (335 mg, yield 27%). mp: 220-222° C.

Workup

  1. waitat 110° C. for 10 minutes
  2. temperatureAfter the reaction mixture was cooled to room temperature
  3. extractionwas extracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. dissolutionWhile The precipitated solid in the reaction mixture was dissolved in chloroform
  7. washwas washed with a saturated aqueous sodium bicarbonate solution, and saturated brine
  8. dry with materialAfter drying over anhydrous sodium sulfate
  9. customthe solvent was removed under reduced pressure
  10. customEach product purified by silica gel column chromatography (hexane/ethyl acetate=1/4)
  11. customthe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-005e2a738d284744bd44c917c56c5f5c
Source dataset
uspto-grants-2013_06
Patent number
US08470814B2

Reaction notes

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