1,4-Dihydro-(1H,4H)-quinoxaline-2,3-diones
J ournal of Medicinal Chemistry, 2001, Vol. 44, No. 12 1961
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ture. After 30 min, saturated ammonium chloride (50 mL) was
added, and the product was extracted into ethyl acetate (2 ×
100 mL). The combined extracts were dried (MgSO4) and
concentrated under reduced pressure. The residues was puri-
fied by flash chromatography (eluting with dichloromethane)
to give 50 (1.86 g, 43%), as a pale yellow solid. H NMR (300
CDCl3) 1.05 (3H, t, J 7 Hz), 1.99 (2H, m), 4.11 (3H, s), 4.12
(3H, s), 5.40 (1H, m), 5.65 (1H, d, J 11 Hz), 7.81 (1H, s).
1
Carbon tetrabromide (466 mg, 1.41 mmol) was added in
portions to a solution 50 (223 mg, 0.70 mmol) and triph-
enylphosphine (369 mg, 1.41 mmol) in dry dichloromethane
(15 mL) at 20 °C. The mixture was stirred for 18 h, and the
solvent was removed under reduced pressure. Purification by
flash chromatography eluting with hexane/dichloromethane
(1:1) gave the title compound (202 mg, 46%), as a white solid,
mp 134-6 °C. 1H NMR (300 MHz, CDCl3) diastereomers
evident: 0.96 (3H, t, J 7 Hz, CH3 both isomers), 2.60 (2H, m,
CH2 minor), 2.80 (2H, m, CH2 major), 4.13 (3H, s, CH3O, both
isomers), 4.18 (3H, s, CH3O, minor), 4.20 (3H, s, CH3O, major),
5.87 (1H, t, J 7 Hz, CH major rotamer), 6.68 (1H, t, J 7 Hz,
CH minor), 7.87 (1H, s, aromatic H both isomers). m/z
(thermospray) 379 (MH+).
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Ack n ow led gm en t. The authors wish to thank Drs.
G.T.G. Swayne and S.G. J ezequel for advice and ac-
knowledge the able assistance of Mrs. N.S. Crouch and
Miss S.-A. Thompson for ligand binding assays, Mr. M.
C. MacKenny for preparing some of the compounds, Dr.
J . Urenjak and Miss M. A. Parry for in vitro functional
assays, Mr. G. Fox and Dr. R. A. O’Donnell for in vivo
assays, and Mr. R. Webster for pharmacokinetic mea-
surements. We also thank the staff of the Physical
Sciences Department for analytical data and measuring
spectroscopic data.
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yields and significant amounts of 38 as a side product.
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