Skip to main content

Advertisement

SpringerLink
Log in

Recent progress in the chemistry of bicyclic 6–6 systems: chemistry of pyrido[1,2-a]pyrimidines

  • Review
  • Published:
Monatshefte für Chemie - Chemical Monthly Aims and scope Submit manuscript

Abstract

The present review provides a study on the structural features, reactions, and synthetic methodologies of pyrido[1,2-a]pyrimidines. Thus, the synthetic procedures and organic reactions since 2000 are described. The aim of this review is to give an overview of the diverse methodologies that have been reported on the chemistry of pyrido[1,2-a]pyrimidines. The tautomeric forms of 2-methyl-3-chloro-9-hydroxypyrido[1,2-a]pyrimidin-4-one are discussed, as well as, the biological importance and mechanistic pathways.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

MCRs:

Multicomponent reactions

equiv.:

Equivalent

CF3SO3H:

Trifluoromethanesulfonic acid

DHPYMT:

Dihydropyrimidinthione

Cu2O:

Cuprous oxide

CuI, CuBr or CuCl:

Cuprous halides

Pd(OAc)2 :

Lead acetate

DPE-Phos:

Bis(2-diphenylphosphinophenyl) ether

TEA:

Triethylamine

CH2Cl2 or DCM:

Dichloromethane

PTSA:

p-Toluene sulfonic acid

POCl3 :

Phosphorus oxychloride

NaN3 :

Sodium azide

NH4OAc:

Ammonium acetate

DMF:

N,N-dimethylformamide

DMF-DMA:

N,N-dimethylformamide dimethyl acetal

DBD:

1,5-Diazabicyclo [4.4.0]dec-5-ene

DBN:

1,5-Diazabicyclo[4.3.0]non-5-ene

DMAD:

Dimethyl acetylenedicarboxylate

EMME:

Ethoxymethylenemalonate diethyl ester

LR:

Lawesson’s reagent

THF:

Tetrahydrofuran

Ph2O:

Diphenyl ether

CS2 :

Carbon disulfide

P2O5 :

Phosphorus pentaoxide

WB:

Water bath

References

  1. Swinbourne JF, Hunt HJ, Klinkert G (1987) Adv Heterocycl Chem 23:103

    Article  Google Scholar 

  2. Hermecz I, Vasvari-Debreczy L, Matyus P (1996) In: Katritzky AR, Rees CW, Scriven EVF (eds), Comprehensive heterocyclic chemistry. Pergamon Press, London, Chapter 8.23, p 563 and references cited therein

  3. Smith RL, Barrett RJ, Sanders-Bush E (1995) J Pharmacol Exp Ther 275:1050

    CAS  Google Scholar 

  4. Awouters F, Vermeire J, Smeyers F, Vermote P, Van Beek R, Niemegeers CJE (1986) Drug Dev Res 8:95

    Article  CAS  Google Scholar 

  5. Matsutani S, Mizushima Y (1989) Preparation and formulation of pyrido[1,2-a]pyrimidine, quinolizin-4-ones, and pyrazino[1,2-a]pyrimidines as antiulcer agents. Eur Pat EP 329126, Aug 23, 1989; (1990) Chem Abstr 112:98557

  6. Doria G, Passarotti C, Magrini R, Forgione A, Sberze P, Corno MTML, Cruzzola G, Cadelli G (1983) Eur J Med Chem 18:227

    CAS  Google Scholar 

  7. Devos C, Dessy F, Hermecz I, Meszaros Z, Breining T (1982) Int Arch Allergy Imm 67:362

    Article  CAS  Google Scholar 

  8. Hermecz I, Meszaros Z (1988) Med Res Rev 8:203

    Article  CAS  Google Scholar 

  9. Colpaert FC (2003) Nat Rev Drug Disc 2:315

    Article  CAS  Google Scholar 

  10. Knoll J, Gyires K, Hermecz I (1987) Drugs Exp Clin Res 13:253

    CAS  Google Scholar 

  11. Kozlovskaya MM, Inozemtsev AN, Nikitin SV, Gochmuradov AG, Yakushev RA, Chabakgorbach R (1995) Bull Exp Biol Med 119:291

    Article  Google Scholar 

  12. Donghi M, Kinzel OD, Summa V (2009) Bioorg Med Chem Lett 19:1930

    Article  CAS  Google Scholar 

  13. Yuan D, Rong R, Yu Z (2008) Huaxue Yu Shengwu Gongcheng 25:13

    Google Scholar 

  14. Ren Q-Y, Wang T, Liu J-C, He H-W (2005) Youji Huaxue 25:1530

    CAS  Google Scholar 

  15. Hermecz I (2003) Adv Heterocycl Chem 85:173

    Article  CAS  Google Scholar 

  16. Hermecz I (1995) Adv Heterocycl Chem 63:103

    Article  CAS  Google Scholar 

  17. Breining T, Hermecz I, Meszaros Z, Toth G, Kajtar M (1978) Magy Kem Lapja 33:432

    CAS  Google Scholar 

  18. Hermecz I, Meszaros Z (1988) Med Res Rev 8:203

    Article  CAS  Google Scholar 

  19. Meszaros Z (1978) Kemiai Kozlemenyek 50:173

    CAS  Google Scholar 

  20. Elattar KM, Rabie R, Hammouda MM (2016) Synth Commun 46:1477

    Article  CAS  Google Scholar 

  21. Elattar KM (2015) Developments in the chemistry of pyrido[1,2-a]pyrimidines. LAP Lambert Academic Publishing, Saarbrücken

    Google Scholar 

  22. Elattar KM, Mert BD (2016) RSC Adv 6:71827

    Article  CAS  Google Scholar 

  23. Fadda AA, El-Hadidy SA, Elattar KM (2015) Synth Commun 45:2765

    Article  CAS  Google Scholar 

  24. Gouda MA, Abu-Hashem AA, Saad HH, Elattar KM (2016) Res Chem Intermed 42:2119

    Article  CAS  Google Scholar 

  25. Fadda AA, Abdel-Galil E, Elattar KM (2015) Synth Commun 45:2053

    Article  CAS  Google Scholar 

  26. Elattar KM, Youssef I, Fadda AA (2016) Synth Commun 46:719

    Article  CAS  Google Scholar 

  27. Koval’chukova OV, Mordovina NI, Kuz’mina NE, Nikitin SV, ZaÏtsev BE, Strashnova SB, Palkina KK (2004) Crystallogr Rep 49:792 (translated from (2004) Kristallografiya 49:880)

  28. Girreser U, Heber D (2000) J Prakt Chem 342:230

    Article  CAS  Google Scholar 

  29. Sato M, Ogasawara H, Kato T (1984) Chem Pharm Bull 32:2602

    Article  CAS  Google Scholar 

  30. Böhm H-J, Klebe G, Kubinyi H (1996) Wirkstoffdesign. Der Weg zum Arzneimittel. Spektrum Akademischer Verlag, Heidelberg, p 159

  31. Peng L, Gao X, Duan L, Ren X, Wu D, Ding K (2011) J Med Chem 54:7729

    Article  CAS  Google Scholar 

  32. Bibas H, Moloney DWJ, Neumann R, Shtaiwi M, Bernhardt PV, Wentrup C (2002) J Org Chem 67:2619

    Article  CAS  Google Scholar 

  33. Wu Y-J, He H, Hu S, Huang Y, Scola PM, Grant-Young K, Bertekap RL, Wu D, Gao Q, Li Y, Klakouski C, Westphal RS (2003) J Med Chem 46:4834

    Article  CAS  Google Scholar 

  34. Nakayama K, Kawato H, Watanabe J, Ohtsuka M, Yoshida K-I, Yokomizo Y, Sakamoto A, Kuru N, Ohta T, Hoshino K, Yoshida K, Ishida H, Cho A, Palme MH, Zhang JZ, Lee VJ, Watkins WJ (2004) Bioorg Med Chem Lett 14:475

    Article  CAS  Google Scholar 

  35. Pryadeina MV, Burgart YV, Kodess MI, Saloutin VI (2005) Russ Chem Bull 54:2841

    Article  CAS  Google Scholar 

  36. Cebasek P, Bevk D, Pirc S, Stanovnik B, Svete J (2006) ACS Comb Sci 8:95

    CAS  Google Scholar 

  37. Shiba SA, El-Ziaty AK, El-Aasar NK, Al-Saman HA (2008) J Chem Res 9:500

    Article  Google Scholar 

  38. Sharma RL, Kour D, Singh J, Kumar S, Gupta P, Gupta S, Kour B, Sachar A (2008) J Heterocycl Chem 45:1775

    Article  CAS  Google Scholar 

  39. Modranka J, Janecki T (2011) Tetrahedron 67:9595

    Article  CAS  Google Scholar 

  40. Yang Y, Shu W-M, Yu S-B, Ni F, Gao M, Wu A-X (2013) Chem Commun 49:1729

    Article  CAS  Google Scholar 

  41. Armstrong RW, Combs AP, Tempest PA, Brown SD, Keating TA (1996) Acc Chem Res 29:123

    Article  CAS  Google Scholar 

  42. Domling A (2006) Chem Rev 106:17

    Article  Google Scholar 

  43. Toure BB, Hall DG (2009) Chem Rev 109:4439

    Article  CAS  Google Scholar 

  44. Ruijter E, Scheffelaar R, Orru RVA (2011) Angew Chem Int Ed 50:6234

    Article  CAS  Google Scholar 

  45. Domling A, Wang W, Wang K (2012) Chem Rev 112:3083

    Article  CAS  Google Scholar 

  46. Adib M, Sayahi MH, Nosrati M, Zhu L-G (2007) Tetrahedron Lett 48:4195

    Article  CAS  Google Scholar 

  47. Namitharan K, Pitchumani K (2013) Adv Synth Catal 355:93

    Article  CAS  Google Scholar 

  48. Yang K, Xiang J, Bao G, Dang Q, Bai X (2013) ACS Comb Sci 15:519

    Article  Google Scholar 

  49. Ryabukhin SV, Plaskon AS, Boron SY, Volochnyuk DM, Tolmachev AA (2011) Mol Divers 15:189

    Article  CAS  Google Scholar 

  50. Sagir H, Rai P, Neha S, Singh PK, Tiwaria S, Siddiqui IR (2016) RSC Adv 6:73924

    Article  CAS  Google Scholar 

  51. Yan Z-F, Quan Z-J, Da Y-X, Zhang Z, Wang X-C (2014) Chem Commun 50:13555

    Article  CAS  Google Scholar 

  52. Sivakumar S, Kumar RR (2014) Asian J Org Chem 3:974

    Article  CAS  Google Scholar 

  53. Jasinski R, Kubik M, Łapczuk-Krygier A, Kacka A, Dresler E, Boguszewska-Czubara A (2014) React Kinet Mech Cat 113:333

    Article  CAS  Google Scholar 

  54. Jasiński R, Ziółkowska M, Demchuk OM, Maziarka A (2014) Cent Eur J Chem 12:586

    Article  Google Scholar 

  55. Adib M, Sayahi MH, Ziyadi H, Bijanzadeh HR, Zhu L-G (2007) Tetrahedron 63:11135

    Article  CAS  Google Scholar 

  56. Adib M, Sayahi MH, Nosratia M, Zhu L-G (2007) Tetrahedron Lett 48:4195

    Article  CAS  Google Scholar 

  57. Bihlmayer G, Derflinger G, Derkosch J, Polansky O (1967) Monatsh Chem 98:564

    Article  CAS  Google Scholar 

  58. Ravina I, Zicane D, Petrova M, Gudriniece E, Kalejs U (2002) Chem Heterocycl Comp 38:836

    Article  CAS  Google Scholar 

  59. Tsanakopoulou M, Cottin T, Buttner A, Sarli V, Malamidou-Xenikaki E, Spyroudis S, Giannis A (2008) Chem Med Chem 3:429

    Article  CAS  Google Scholar 

  60. Toche RB, Ghotekar BK, Kazi MA, Patil SP, Jachak MN (2008) Schol Res Exch. Article ID 434329

  61. Jie-Jack L (2005) Name reactions in heterocyclic chemistry. Wiley, New York, NY, p 255

    Google Scholar 

  62. Chen X, Zhu D, Wang X, Yan S, Lin J (2013) Tetrahedron 69:9224

    Article  CAS  Google Scholar 

  63. Shidlovskii AF, Sizov AY, Kuleshova LN, Nesterov VV, Antipin MY, Peregudov AS, Chkanikov ND (2000) Russ Chem Bull Int Ed 49:1257

    Article  CAS  Google Scholar 

  64. Cocco MT, Congiu C, Onnis V (2001) Chem Pharm Bull 49:703

    Article  CAS  Google Scholar 

  65. Shidlovskii AF, Peregudov AS, Averkiev BB, Antipin MY, Chkanikov ND (2004) Russ Chem Bull Int Ed 53:2060

    Article  CAS  Google Scholar 

  66. Abu-Shanab FA, Hessen A, Gaber H, Mousa SAS (2006) J Sulfur Chem 27:293

    Article  CAS  Google Scholar 

  67. Shidlovskii AF, Peregudov AS, Averkiev BB, Antipin MY, Chkanikov ND (2004) Izv Akad Nauk Ser Khim 53:1977

    Google Scholar 

  68. Shidlovskii AF, Sizov A Yu, Kuleshova LN, Nesterov VV, Antipin MY, Peregudov AS, Chkanikov ND (2000) Izv Akad Nauk Ser Khim 49:1261

  69. Shidlovskii AF, Peregudov AS, Bulychev YuN, Chkanikov ND (2009) Pharm Chem J 43:549

    Article  CAS  Google Scholar 

  70. Harriman GCB, Chi S, Zhang M, Crowe A, Bennett RA, Parsons I (2003) Tetrahedron Lett 44:3659

    Article  CAS  Google Scholar 

  71. Barykina-Tassa OV, Snider BB (2015) Tetrahedron Lett 56:3151

    Article  CAS  Google Scholar 

  72. Girreser U, Heber D, Schütt M (1998) Synlett 263

  73. Girreser U, Bluhm U, Clement B, Heber D (2013) Magn Reson Chem 51:714

    CAS  Google Scholar 

  74. Bluhm U, Boucher J-L, Buss U, Clement B, Friedrich F, Girreser U, Heber D, Lam T, Lepoivre M, Rostaie-Gerylow M, Wolschendorf U (2009) Eur J Med Chem 44:2877

    Article  CAS  Google Scholar 

  75. Helmy NM (2006) Synthesis of polyfunctional heterocycles using microwave as environmentally friendly technique. PhD Thesis, Cairo University, Cairo, Egypt

  76. Helmy NM, El-Baih FEM, Al-Alshaikh MA, Moustafa MS (2011) Molecules 16:298

    Article  CAS  Google Scholar 

  77. Suri OP, Suri KA, Gupta BD, Satti NK (2002) Synth Commun 32:741

    Article  CAS  Google Scholar 

  78. Basahel SN, Ahmed NS, Narasimharao K, Mokhtar M (2016) RSC Adv 6:11921

    Article  CAS  Google Scholar 

  79. Hammouda M, AbouZeid ZM, Metwally MA (2005) Chem Heterocycl Comp 41:1525

    Article  CAS  Google Scholar 

  80. Bonacorso HG, Righi FJ, Rodrigues IR, Cechinel CA, Costa MB, Wastowski AD, Martins MAP, Zanatta N (2006) J Heterocycl Chem 43:229

    Article  CAS  Google Scholar 

  81. Chanu LG, Singh TP, Jang YJ, Yoon Y-J, Singh OM, Lee S-G (2014) Bull Korean Chem Soc 35:994

    Article  CAS  Google Scholar 

  82. Hajimahdi Z, Zarghi A, Zabihollahi R, Aghasadeghi MR (2013) Med Chem Res 22:2467

    Article  CAS  Google Scholar 

  83. Abass M, Ismail MM, Abdel-Monem WR, Mayas AS (2010) Chem Pap 64:72

    Article  CAS  Google Scholar 

  84. Gullu M, Uzun S, Yalcin S (2003) Tetrahedron Lett 44:1939

    Article  CAS  Google Scholar 

  85. Saxena AS, Goel A, Ram VJ (2003) J Indian Chem Soc 80:311

    CAS  Google Scholar 

  86. Merja BC, Joshi AM, Parikh KA, Parikh AR (2004) Indian J Chem 43B:909

    CAS  Google Scholar 

  87. Pawde AV, Ubale PN, Vartale SP (2015) World J Pharm Res 4:1502

    CAS  Google Scholar 

  88. Singh OM, Ahmed MF (2004) Indian J Chem 43B:1561

    CAS  Google Scholar 

  89. Esmaeili AA, Salehan F, Habibi A, Fakhari AR (2016) Tetrahedron Lett 57:100

    Article  CAS  Google Scholar 

  90. Liang F, Zhang J, Tan J, Liu Q (2006) Adv Synth Catal 348:1986

    Article  CAS  Google Scholar 

  91. Ingalls EA, Popp FD (1967) J Heterocycl Chem 4:523

    Article  CAS  Google Scholar 

  92. Abass M (2000) Synth Commun 30:2735

    Article  CAS  Google Scholar 

  93. Tschitschibabin AE (1924) Chem Ber 57:1168

    Article  Google Scholar 

  94. Snyder HR, Robison MM (1952) J Am Chem Soc 74:4910

    Article  CAS  Google Scholar 

  95. Katritzky AR, Waring AJ (1962) J Chem Soc 1540

  96. Claremon DA, McCauley JA, Liverton NH, Theberge CR (2002) Preparation of iminopyrimidine derivatives as NMDA NR2B receptor antagonists. US Patent 20020013329, Jan 31, 2002; (2002) Chem Abstr 136:69819

  97. Roma G, Braccio MD, Leoncini G, Aprile B (1993) Il Farmaco 48:1225

    CAS  Google Scholar 

  98. Roma G, Cinone N, Braccio MD, Grossi G, Leoncini G, Singnorelleo MG, Carotti A (2000) Bioorg Med Chem 8:751

    Article  CAS  Google Scholar 

  99. Roma G, Cinone N, Braccio MD, Grossi G, Leoncini G, Singnorelleo MG, Carotti A (2001) Bioorg Med Chem 9:555

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Mansoura University, El-Gomhoria Street, Mansoura, 35516, Egypt

    Khaled M. Elattar, Ramy Rabie & Mohamed M. Hammouda

Authors
  1. Khaled M. Elattar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ramy Rabie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohamed M. Hammouda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khaled M. Elattar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elattar, K.M., Rabie, R. & Hammouda, M.M. Recent progress in the chemistry of bicyclic 6–6 systems: chemistry of pyrido[1,2-a]pyrimidines. Monatsh Chem 148, 601–627 (2017). https://doi.org/10.1007/s00706-016-1852-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00706-016-1852-1

Keywords

Search

Navigation