Chinese Journal of Organic Chemistry >
N-Alkylation and O-Alkylation of Ethyl 4-(4,6-Dimethoxy-pyrimidin-2-yl)-2-oxo-1,2-dihydroquinoline-3-carboxylate
Received date: 2013-06-04
Revised date: 2013-07-18
Online published: 2013-07-26
Supported by
Project supported by the Planned Science and Technology Project of Hunan Province (No. 2012NK3098), the Scientific Research Fund of Hunan Provincial Education Department (No. 11A092) and the Planned Science and Technology Project of Huaihua City (No. 2013).
Twenty novel N-substitued and O-substitued compounds were prepared starting from ethyl 4-(4, 6-dimethoxy-py-rimidin-2-yl)-2-oxo-1, 2-dihydroquinoline-3-carboxylate. Various halogenated hydrocarbons were used as resource of alkylation and NaH as base in N, N-dimethylformamide (DMF) at room temperature. The structures of alkylation products were confirmed by 1H NMR, IR, MS and elemental analysis. Two isomer structures were further determined by representative X-ray structures of N10 and O10. The alkylation reaction was performed in mild conditions with a total yield of 89%～98%. Among them, the main product N-Alkylation was obtained in 47%～77% yield, and O-Alkylation was simultaneously obtained in 21%～49% yield by a simple one-pot reaction.
Key words： quinolinone; alkylation; structural characterization
Li Yuanxiang . N-Alkylation and O-Alkylation of Ethyl 4-(4,6-Dimethoxy-pyrimidin-2-yl)-2-oxo-1,2-dihydroquinoline-3-carboxylate[J]. Chinese Journal of Organic Chemistry, 2013 , 33(11) : 2334 -2340 . DOI: 10.6023/cjoc201306004
[1] (a) Khalid,E.S.; Mansour,S.A.S.; Farouk,S.E.F.; Samir,A.R.J.Nat.Prod.2000,63,995.
(b) He,J.; Lion,U.; Sattler,I.; Gollmick,F.A.; Grabley,S.; Cai,J.M.; Meiners,M.; SchÜnke,H.; Schaumann,K.; Dechert,U.; Krohn,M.J.Nat.Prod.2005,68,1397.
[2] (a) Payne,J.E.; Bonnefous,C.; Symons,K.T.; Nguyen,P.M.; Sablad,M.; Rozenkrants,N.; Zhang,Y.; Wang,L.; Yazdani,N.; Shiau,A.K.; Noble,S.A.; Rix,P.; Rao,T.S.; Hassig,C.A.; Smith,N.D.J.Med.Chem.2010,53,7739.
(b) Liu,Q.S.; Chang,J.W.; Wang,J.H.; Kang,S.A.; Thoreen,C.C.; Markhard,A.; Hur,W.; Zhang,J.M.; Sim,T.; Sabatini,D.M.; Gray,N.S.J.Med.Chem.2010,53,7146.
(c) Lucas,S.; Negri,M.; Heim,R.; Zimmer,C.; Hartmann,R.W.J.Med.Chem.2011,54,2307.
(d) Yin,L.; Lucas,S.; Maurer,F.; Kazmaier,U.; Hu,Q.Z.; Hartmann,R.W.J.Med.Chem.2012,55,6629.
[3] Vrudhula,V.M.; Dasgupta,B.; Qian-Cutrone,J.; Kozlowski,E.S.; Boissard,C.G.; Dworetzky,S.I.; Wu,D.; Gao,Q.; Kimura,R.; Gribkoff,V.K.; Starrett,J.E.J.Med.Chem.2007,50,1050.
[4] Freeman,G.A.; C.Andrews,W.; Hopkins,A.L.; Lowell,G.S.; Schaller,L.T.; Cowan,J.R.; Gonzales,S.S.; Koszalka,G.W.; Hazen,R.J.; Boone,L.R.; Ferris,R.G.; Creech,K.L.; Roberts,G.B.; Short,S.A.; Weaver,K.; Reynolds,D.J.; Milton,J.; Ren,J.; Stuart,D.I.; Stammers,D.K.; Chan,J.H.J.Med.Chem.2004,47,5923.
[5] Anerson,R.J.; Cloudsdale,L.S.; Hokama,T.EP 0461079,1991 [Chem.Abstr.1991,116,128972].
[6] (a) Detsi,A.; Bouloumbasi,D.; Prousis,K.C.; Koufaki,M.; Athanasellis,G.; Melagraki,G.; Afantitis,A.; Igglessi-Markopoulou,O.; Kontogiorgis.C.; Hadjipavlou-Litina,D.J.J.Med.Chem.2007,50,2450.
(b) Ryckebusch,A.; Garcin,D.; Lansiaux,A.; Goossens,J.F.; Baldeyrou,B.; Houssin,R.; Bailly,C.; Hénichart,J.P.J.Med.Chem.2008,51,3617.
[7] Marzano,C.; Chilin,A.; Baccichetti,F.; Bettio,F.Eur.J.Med.Chem.2004,39,411.
[8] (a) Ukrainets,I.V.; Sidorenko,L.V.; Gorokhova,O.V.; Bereznyakova,N,L.; Shishkina,S.V.Chem.Heterocycl.Compd.2006,42,1296.
(b) Ukrainets,I.V.; Bereznyakova,N.L.; Parshikov,V.A.; Turov,A.V.Chem.Heterocycl.Comp.2007,43,1269.
[9] Ali,I.A.I.; Fathalla,W.; Rayes,S.M.E.ARKIVOC 2008,13,179.
[10] Ahvale,A.B.; Prokopcová.H.; Šef?ovi?ová,J.; Steinschifter.W.; Täubl,A.E.; Uray.G.; Stadlbauer,W.Eur.J.Org.Chem.2008,563.
[11] Woo,L.W.L.; Ganeshapillai,D.; Thomas,M.P.; Sutcliffe,O.B.; Malini,B.; Mahon,M.F.; Purohit,A.; Potter,B.V.L.ChemMedChem 2011,6,2019.
[12] (a) Priya,N.; Gupta,A.; Chand,K.; Singh,P.; Kathuria,A.; Raj,H.G.; Parmar,V.S.; Sharma,S.K.Bioorg.Med.Chem.2010,18,4085.
(b) Chilin,A.; Marzano,C.; Baccichetti,F.; Simonato,M.; Guiotto,A.Bioorg.Med.Chem.2003,11,1311.
(c) Park,K.K.; Lee,J.J.Tetrahedron.2004,60,2993.
[13] Peifer,C.; Urich,R.; Schattel,V.; Abadleh,M.; Röttig,M.; Kohlbacher,O.; Laufer,S.Bioorg.Med.Chem.Lett.2008,18,1431.
[14] (a) Merabet,N.; Dumond,J.; Collinet,B.; Baelinghem,L.V.; Boggetto,N.; Ongeri,S.; Ressad,F.; Reboud-Ravaux,M.; Sicsic,S.J.Med.Chem.2004,47,6392.
(b) Guo,Z.X.; Cainmldge,A.N.; McKⅡlop,A.; Horwell,D.C.Tetrahedron Lett.1999,40,6999.
(c) Geneste,H.; Backfisch,G.; Braje,W.; Delzer,J.; Haupt,A.; Hutchins,C.W.; King,L.L.; Lubisch,W.; Steiner,G.; Teschendorf,H.J.; Ungera,L.; Wernet,W.Bioorg.Med.Chem.Lett.2006,16,658.
[15] Li,Y.X.; Yan,X.H.; Hu,W.Y.Spec.Petrochem.2011,28(5),57 (in Chinese).(李元祥,晏小红,胡蔚昱,精细石油化工,2011,28(5),57.)
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