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DOI: 10.1055/s-0029-1217984
Synthesis of Bicyclic Pyridones via Cyclocondensation of Heterocyclic Ketene Aminals with β-Ketoester Enol Tosylates
Publication History
Publication Date:
24 September 2009 (online)
Abstract
A series of novel bicyclic pyridones were easily prepared by cyclic condensation of heterocyclic ketene aminals with β-keto ester enol tosylates in the presence of a base to give products in excellent yields (80-95%).
Key words
pyridones - cyclocondensation - heterocyclic ketene aminals - β-keto ester enol tosylates
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1a
Huang Z.-T.Wang M.-X. Heterocycles 1994, 37: 1233 -
1b
Huang Z.-T.Wang M.-X. Prog. Nat. Sci. 1999, 11: 971 -
2a
Gupta AK.Ila H.Junjappa H. Synthesis 1988, 284 -
2b
Huang Z.-T.Liu Z.-R. Chem. Ber. 1989, 122: 95 -
2c
Zhang J.-H.Wang M.-X.Huang Z.-T. J. Chem. Soc., Perkin Trans. 1 1999, 321 -
2d
Nie X.-P.Wang M.-X.Huang Z.-T. Synthesis 2000, 1439 -
2e
Yu C.-Y.Wang L.-B.Li W.-Y.Huang Z.-T. Synthesis 1996, 959 - 3
Jones RCF.Patel P.Hirst SC.Turner I. Tetrahedron 1997, 53: 11781 -
4a
Huang Z.-T.Liu Z.-R. Heterocycles 1986, 24: 2247 -
4b
Jones RCF.Patel P.Hirst SC.Smallridge MJ. Tetrahedron 1998, 54: 6191 -
4c
Jones RCF.Smallridge MJ. Tetrahedron Lett. 1988, 29: 5005 -
4d
Yaqub M.Yu C.-Y.Jia Y.-M.Huang Z.-T. Synlett 2008, 1357 -
4e
Yu C.-Y.Yang P.-H.Zhao M.-X.Huang Z.-T. Synlett 2006, 1835 -
4f
Yu C.-Y.Yan S.-J.Huang Z.-T. Acta Crystallogr., Sect. E: Struct. Rep. Online 2006, 62: o2731 - 5
Zhang J.-H.Wang M.-X.Huang Z.-T. J. Chem. Soc., Perkin Trans. 1 1999, 2087 -
6a
Huang Z.-T.Tzai LH. Chem. Ber. 1986, 119: 2208 -
6b
Huang Z.-T.Liu Z.-R. Synth. Commun. 1989, 19: 1801 -
6c
Huang Z.-T.Wang M.-X. J. Chem. Soc., Perkin Trans. 1 1993, 1085 -
6d
Zhao M.-X.Wang M.-X.Huang Z.-T. Tetrahedron 2002, 58: 1309 -
6e
Wang L.-B.Huang Z.-T. Synth. Commun. 1997, 27: 409 -
6f
Huang Z.-T.Wang X.-J. Chem. Ber. 1987, 120: 1803 -
6g
Takao T.Satomi N. Bull. Chem. Soc. Jpn. 1993, 66: 2118 - 7
Liao J.-P.Zhang T.Yu C.-Y.Huang Z.-T. Synlett 2007, 761 - 8
Yu C.-Y,Yan S.-J,Zhang T, andHuang Z.-T. inventors; CN101041660. - 9
Xu Z.-H.Jie Y.-F.Wang M.-X.Huang Z.-T. Synthesis 2002, 523 -
10a
Tieman CH,Kollmeyer WD, andRoman SA. inventors; DE 2,445,421. -
10b
Tieman CH, andKollmeyer WD. inventors; US 3,948,934. -
10c
Porter PE, andKollmeyer WD. inventors; US 4,053,623. -
11a
Jordan AD.Vaidya AH.Rosenthal DI.Dubinsky B.Kordik CP.Sanfilippo PJ.Wub WN.Reitza AB. Biomed. Chem. Lett. 2002, 12: 2381 -
11b
Maryanoff BE.Nortey SO.McNally JJ.Sanfilippo PJ.McComsey DF.Dubinsky B.Shank RP.Reitz AB. Biomed. Chem. Lett. 1999, 9: 1547 -
11c
Kondo H.Taguchi M.Inoue Y.Sakamoto F.Tsukamoto G. J. Med. Chem. 1990, 33: 2012 -
11d
Maryanoff BE.Ho W.McComsey DF.Reitz AB.Grow PP.Nortey SO.Shank RP.Dubinsky B.Taylor RJ.Gardocki JF. J. Med. Chem. 1995, 38: 16 - 12
Suryawanshi SN.Pandey S. .Bhatt BA.Gupta S. Eur. J. Med. Chem. 2007, 511 - 13
Abdelhalima MM.El-Saidib MMT.Rabieb ST.ElmegeedaG A. Steroids 2007, 72: 459 -
14a
Kubo K.Ito N.Isomura Y.Sozu I.Homma H.Murakami M. Chem. Pharm. Bull. 1979, 27: 1207 -
14b
Frohn MJ,Hong F.-T,Liu L,Lopez P,Siegmund AC,Tadesse S, andTamayo N. inventors; WO 2005070932. -
14c
Alonso-Alija C,Michels M,Schirok H,Schlemmer K.-H,Dodd S,Fitzgerald M,Bell J, andGill A. inventors; WO 2003053967. - 15
Hehemann DG.Winnik W. J. Heterocycl. Chem. 1994, 31: 393 -
16a
Cheng D.-C.Croft L.Abdi M.Lightfoot A.Gallagher T. Org. Lett. 2007, 9: 5175 -
16b
Cheng D.-C.Gallagher T. Org. Lett. 2009, 11: 2639 -
16c
Qacemi ME.Ricard L.Zard SZ. Chem. Commun. 2006, 4422 -
16d
Podhorez DE. J. Heterocycl. Chem. 1991, 28: 971 -
16e
Sylvia S.Daniel S.Simon S.Zhang X.Volkhard A. Synthesis 2005, 3107 -
17a
Tilak BD.Ayyangar NR.Rao US. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1984, 23: 24 -
17b
Jones RCF.Dimopoulos P.Coles SC.Light ME.Hursthouse MB. J. Chem. Soc., Perkin Trans. 1 2000, 2331 -
17c
Masahiko T.Chiyoshi N.Yoshio S. Chem. Lett. 1987, 1229 -
17d
Al-Afaleq E. Synth. Commun. 2001, 31: 3557 -
18a
Hansen LA.Skrydstrup T. J. Org. Chem. 2005, 70: 5997 -
18b
Jalander L.Mattinen J.Oksanen L.Rosling A. Synth. Commun. 1990, 20: 881
References and Notes
General Procedure
for the Cyclocondensation Reaction
A 50 mL round-bottom
flask was charged with β-keto ester enol tosylates 2 (1 mmol), 1,4-dioxane (10 mL), and Et3N
(3 mL), then the solution was added to HKA 1 (1
mmol), and the solution was refluxed. The resulting solution was
stirred for 3-14 h until the β-keto ester enol
toslates 2 were completely consumed. The
mixture was quenched by the addition of H2O (50 mL).
The reaction mixture was filtered off, and the residue was washed
with H2O to give a crude product that was recrystallized
by EtOH or acetone to form the final products 4-6.
Compound 4d:
yellow solid; mp 184-187.5 ˚C. IR (KBr): 3366
(NH), 3079 (C=CH), 1679 (C=O), 1602 (C=O),
1558 (C=C), 1324 (CN), 1165 (CF) cm-¹. ¹H
NMR (500 MHz, DMSO-d
6): δ = 3.68
(t, J = 9.2
Hz, 2 H, CH2), 4.11 (t, J = 9.1
Hz, 2 H, CH2), 6.00 (s, 1 H, CH=), 7.56-7.79
(m, 5 H, ArH, NH). ¹³C NMR (125 MHz,
DMSO-d
6): δ = 42.6 (NCH2),
43.7 (NCH2), 91.8 (CCOAr),
104.3 (CHCO), 122.5 (q, J = 211.3
Hz, CF3), 128.5 (2 × CHar),
131.1 (2 × CHar), 137.0 (Car),
137.8 (Car), 140.0 (q, J = 30
Hz, CCF3), 154.4 (C=CCOAr), 159.0 (C=O),
190.2 (COAr). HRMS (TOF
ES-): m/z calcd for C15H9ClF3N2O2 [M - H+]:
341.0310; found: 341.0308.
CCDC 738457 contains the supplementary crystallographic data for compound 4d. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif.