Methane → 6-Fluoro-1,4-dihydro-2,3-quinoxalinedione

HRID 54305

Reaction equation

HRID 54305 reaction equation
[C:1]([O:8]CC)(=O)[C:2]([O:4]CC)=O.[F:11][C:12]1[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([NH2:19])[CH:13]=1.C>[OH-].[Na+]>[F:11][C:12]1[CH:13]=[C:14]2[C:15](=[CH:16][CH:17]=1)[NH:18][C:1](=[O:8])[C:2](=[O:4])[NH:19]2

Participants

5

Reactant 3

HCID 297MethaneHCID 7268Diethyl OxalateHCID 1645844-Fluorobenzene-1,2-diamine

Product 1

HCID 6019536-Fluoro-1,4-dihydro-2,3-quinoxalinedione

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

The title compound (Sarges, R. et al., J. Med. Chem. 33:2240 (1990)) was prepared using an adaptation of the method of Cheeseman. (Cheeseman, G. W. H. J. Chem. Soc. 1171 (1962)). A mixture of diethyl oxalate (17.4 g, 0.100 mol) and 4-fluoro-1,2-diaminobenzene (1.00 g, 7.93 mmol) was heated to reflux with stirring under N2 for 2 h. The reaction was cooled to room temperature and the solid was collected by vacuum filtration and rinsed with EtOH (50 mL) to give a gray-brown solid which was further dried under vacuum (0.1 torr, 25° C.) to yield 1.06 g (74.4%) which was >98% pure by NMR. An analytically pure sample was prepared by dissolution of 60 mg of the solid in 1.0N NaOH and treatment of this solution with activated charcoal. Filtration of this mixture through a pad of Celite and acidification with 1N HCl gave fine white needles which were collected by vacuum filtration, rinsed with H2O and further dried under vacuum (0.1 torr, 25° C.) to give 25.5 mg of white needles, mp 375°-380° C. (dec) (lit.>300° C. (Sarges, R., et al., J. Med. Chem. 33:2240 (1990)). 1H NMR (d6 -DMSO) δ6.90 (m, 2H, ArH), 7.09 (dd, J=9, J=5.4), 11.9 (s, 1H, NH), 11.96 (s, 1H, NH). EIMS m/z180(100,M+), 152(44), 124(63), 97(43), 28(53). EIHRMS calc. for C8H5FN2N2O2 180.0334, found 180.0337.

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. filtrationthe solid was collected by vacuum filtration
  4. washrinsed with EtOH (50 mL)
  5. customto give a gray-brown solid which
  6. customwas further dried under vacuum (0.1 torr, 25° C.)
  7. customto yield 1.06 g (74.4%) which
  8. filtrationFiltration of this mixture through a pad of Celite and acidification with 1N HCl
  9. customgave fine white needles which
  10. filtrationwere collected by vacuum filtration
  11. washrinsed with H2O
  12. customfurther dried under vacuum (0.1 torr, 25° C.)

Sources & evidence

ORD record
ord-8769313776634965b5e0007e58e882b3
Source dataset
uspto-grants-1997_04
Patent number
US05622952

Linked notes

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