Pyridine → 5-[3-(5-oxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione

HRID 1622317Notes

Reaction equation

HRID 1622317 reaction equation
[OH:1][NH:2][C:3]([C:5]1[CH:6]=[C:7]([N:11]2[C:17](=[O:18])[CH2:16][C:15](=[O:19])[NH:14][C:13]3[C:20]4[C:25]([CH:26]=[CH:27][C:12]2=3)=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH:8]=[CH:9][CH:10]=1)=[NH:4].N1C=CC=CC=1.[C:34](Cl)(=O)[O:35]C1C=CC=CC=1.C1CCN2C(=NCCC2)CC1>ClCCl.O>[O:35]=[C:34]1[O:1][N:2]=[C:3]([C:5]2[CH:6]=[C:7]([N:11]3[C:17](=[O:18])[CH2:16][C:15](=[O:19])[NH:14][C:13]4[C:20]5[C:25]([CH:26]=[CH:27][C:12]3=4)=[CH:24][CH:23]=[CH:22][CH:21]=5)[CH:8]=[CH:9][CH:10]=2)[NH:4]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 1785133085-[3-(N-hydroxyamidino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione

Product 1

HCID 1359570545-[3-(5-oxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dioneYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 5-[3-(N-hydroxyamidino)phenyl]-1H-naphtho[1,2-b][1,4]diazepin-2,4(3H,5H)-dione (36 mg, 0.1 mmol) in dichloromethane (18 mL) was added pyridine (0.012 mL, 0.15 mmol) and phenyl chlorocarbonate (0.016 mL, 0.13 mmol). The reaction mixture was stirred at room temperature for 1.5 hours, and cold water was added. After the mixture was stirred for 20 min, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. A suspension of the obtained pale yellow crystal in acetonitrile (10 mL) was added 1,8-diazabicyclo[5,4,0]-7-undecene (0.03 mL, 0.2 mmol), stirred at room temperature for 15 minuets. After the solvent was removed, the residue was purified by silica gel column chromatography (chloroform/methanol=10/1) to give a pale yellow crystal. The crystal was washed with chloroform to give the titled compound as white crystal (20 mg, yield 52%).

Workup

  1. stirringAfter the mixture was stirred for 20 min
  2. washthe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was removed under reduced pressure
  5. additionA suspension of the obtained pale yellow crystal in acetonitrile (10 mL)
  6. stirringstirred at room temperature for 15 minuets
  7. customAfter the solvent was removed
  8. customthe residue was purified by silica gel column chromatography (chloroform/methanol=10/1)
  9. customto give a pale yellow crystal
  10. washThe crystal was washed with chloroform

Sources & evidence

ORD record
ord-a8091a43591546d3bcfb26b927f50870
Source dataset
uspto-grants-2014_07
Patent number
US08778933B2

Reaction notes

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