Skip to main content
SpringerLink
Log in

Convenient synthesis of 2-substituted 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-ones

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

Abstract

A new synthetic route was elaborated at our laboratory providing a convenient access to 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-ones (diazaoxindoles), a compound family of biological relevance. Treatment of the easily available ethyl 2-(4-chloropyrimidin-5-yl)acetate derivatives with ammonia afforded the corresponding 2-(4-aminopyrimidin-5-yl)acetamides, which were finally cyclized to the target compounds.

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

Similar content being viewed by others

References

  1. Shepherd TA, Dally RD, Joseph S (2010) Akt and p70 S6 kinase inhibitors. US Patent Appl. US 2010120801, 13 May 2010

  2. Shepherd TA, Dally RD, Joseph S (2010) Akt and p70 S6 kinase inhibitors. PCT Int. Pat. Appl. WO 2010056563, 20 May 2010

  3. Shepherd TA, Dally RD, Joseph S (2010) Chem Abstr 152:568154

    Google Scholar 

  4. Mitchell IS, Spencer KL, Stengel P, Han Y, Kallan NC, Munson M, Vigers GPA, Blake J, Piscopio A, Josey J, Miller S, Xiao D, Xu R, Rao C, Wang B, Bernacki AL (2005) Akt protein kinase inhibitors. PCT Int. Patent Appl. WO 2005051304, 9 June 2005

  5. Mitchell IS, Spencer KL, Stengel P, Han Y, Kallan NC, Munson M, Vigers GPA, Blake J, Piscopio A, Josey J, Miller S, Xiao D, Xu R, Rao C, Wang B, Bernacki AL (2005) Chem Abstr 143:40007

    Google Scholar 

  6. Follmann M, Stasch J-P, Redlich G, Lang D, Vakalopoulos A, Wunder F, Tersteegen A (2014) Trifluoromethyl-substituted fused pyrimidines and their use. US Patent Appl. US 2014249168, 4 Sep 2014

  7. Follmann M, Stasch J-P, Redlich G, Lang D, Vakalopoulos A, Wunder F, Tersteegen A (2014) Chem Abstr 161:404656

    Google Scholar 

  8. Follmann M, Stasch J-P, Redlich G, Ackerstaff J, Griebenow N, Knorr A, Wunder F, Li VM-J, Kroh W, Baerfacker L (2012) Ring-fused pyrimidines and triazines and use thereof for the treatment and/or prophylaxis of cardiovascular diseases. PCT Int. Patent Appl. WO 2012004258, 12 Jan 2012

  9. Follmann M, Stasch J-P, Redlich G, Ackerstaff J, Griebenow N, Knorr A, Wunder F, Li VM-J, Kroh W, Baerfacker L (2012) Chem Abstr 156:175315

    Google Scholar 

  10. Raghavan S, Stelmach JE, Smith CJ, Li H, Whitehead A, Waddell ST, Chen Y-H, Miao S, Ornoski OA, Garfunkle J, Liao X, Chang J, Han X, Guo J, Groeper JA, Brockunier LL, Rosauer K, Parmee ER (2011) Soluble guanylate cyclase activators. PCT Int. Patent Appl. WO 2011149921, 1 Dec 2011

  11. Raghavan S, Stelmach JE, Smith CJ, Li H, Whitehead A, Waddell ST, Chen Y-H, Miao S, Ornoski OA, Garfunkle J, Liao X, Chang J, Han X, Guo J, Groeper JA, Brockunier LL, Rosauer K, Parmee ER (2011) Chem Abstr 155:11159

    Google Scholar 

  12. Joule JA, Mills K (2000) Heterocyclic chemistry, 4th edn. Blackwell Science Ltd, Oxford, p 218

    Google Scholar 

  13. Sun CL, Li X, Zhu Y (2009) Bioactive compounds for treatment of cancer and neurodegenerative diseases. PCT Int. Patent Appl. WO 2009139834, 19 Nov 2009

  14. Sun CL, Li X, Zhu Y (2009) Chem Abstr 151:571128

    Google Scholar 

  15. Choi H-S, Wang Zh, Richmond W, He X, Yang K, Jiang T, Sim T, Karanewsky D, Gu X, Zhou V, Liu Y, Ohmori O, Caldwell J, Graya N, Hea Y (2006) Bioorg Med Chem Lett 16:2173

    Article  CAS  Google Scholar 

  16. Neelamkavil SF, Boyle CD, Harris JM, Stamford AW, Hao J, Neustadt BR, Chackalamannil S, Xia Y, Greenlee WJ (2010) Bicyclic heterocycle derivatives and their use as GPCR modulators. PCT Int. Patent Appl. WO 2010009207, 21 Jan 2010

  17. Neelamkavil SF, Boyle CD, Harris JM, Stamford AW, Hao J, Neustadt BR, Chackalamannil S, Xia Y, Greenlee WJ (2010) Chem Abstr 152:192137

    Google Scholar 

  18. Leftheris K, Barrish J, Hynes J, Wrobleski ST (2002) Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors. PCT Int. Patent Appl. WO 2002040486, 23 May 2002

  19. Leftheris K, Barrish J, Hynes J, Wrobleski ST (2002) Chem Abstr 136:386144, also published as: EP 1363910

  20. Johnson TB, Peck HT, Ambler JA (1911) J Am Chem Soc 33:758

    Article  CAS  Google Scholar 

  21. Vaid RK, Spitler JT, Boini S, May SA, Hoying RC (2012) Synthesis 44:2396

    Article  CAS  Google Scholar 

  22. Hennequin LFA, Ple P, Lohmann JM, Thomas AP (1999) Oxindolylquinazoline derivatives as angiogenesis inhibitors. PCT Int. Patent Appl. WO 1999010349, 3 Mar 1999

  23. Hennequin LFA, Ple P, Lohmann JM, Thomas AP (1999) Chem Abstr 130:209715

    Google Scholar 

  24. Hunt JT, Bhide RS, Borzilleri RM, Qian L (2000) Pyrrolotriazine inhibitors of kinases. PCT Int. Patent Appl. WO 2000071129, 30 Nov 2000

  25. Hunt JT, Bhide RS, Borzilleri RM, Qian L (2000) Chem Abstr 134:17506

    Google Scholar 

  26. Biggs J, Sykes P (1959) J Chem Soc 1849

  27. Andersag H, Westphal K (1937) Chem Ber 70:2035

    Article  Google Scholar 

  28. Cereced LR, Pickel FD (1937) J Am Chem Soc 59:1714

    Article  Google Scholar 

  29. Cheung M, Harris PA, Lackey KE (2001) Tetrahedron Lett 42:999

    Article  CAS  Google Scholar 

  30. Massaroli GG, Signorelli G (1966) Boll Chim Pharm 105:400

    CAS  Google Scholar 

  31. Zymalkowski F, Reimann F (1966) Arch Pharm 299:362

    Article  CAS  Google Scholar 

  32. Holmes IP, Bergman Y, Lunniss GE, Nikac M, Choi N, Hemley CF, Walker SR, Foitzik RCh, Ganame D, Lessene R (2012) FAK inhibitors. PCT Int. Patent Appl. WO 2012110773, 23 Aug 2012

  33. Holmes IP, Bergman Y, Lunniss GE, Nikac M, Choi N, Hemley CF, Walker SR, Foitzik RCh, Ganame D, Lessene R (2012) Chem Abstr 157:382910

    Google Scholar 

  34. Gravin AI (1943) Zhurnal Prikladnoi Khimii. Russian Federation, Sankt-Petersburg, p 105

    Google Scholar 

  35. Gravin AI (1944) Chem Abstr 38:8327

    Google Scholar 

  36. Andersag H, Westphal K (1945) Pyrimidine derivatives and process of preparing the same. US Patent 2,377,395, 5 June 1945

  37. Andersag H, Westphal K (1946) Chem Abstr 40:570

    Google Scholar 

  38. Verma SD, Dey AN (1963) J Indian Chem Soc 40:283

    CAS  Google Scholar 

  39. Verma SD, Dey AN (1963) Chem Abstr 59:41697

    Google Scholar 

  40. Hermecz I, Kereszturi G, Vasvari-Debreczy L (1992) Advances in heterocyclic chemistry. Academic Press Inc, San Diego, p 141

    Google Scholar 

  41. Peters E, Minnemeyer HJ, Spears AW, Tickelmann H (1960) J Org Chem 25:2137

    Article  CAS  Google Scholar 

  42. Partyka RA (1965) N,N′-Bis(pyrimidine-5-acetyl)ethylene diamines. US Pat. US 3,225,047, 21 Dec 1965

  43. Partyka RA (1966) Chem Abstr 64:35926

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, PO Box 91, 1521, Budapest, Hungary

    Eszter Kókai, József Nagy, Tünde Tóth, József Kupai & Péter Huszthy

  2. Directorate of Drug Substance Development, EGIS Pharmaceuticals Plc., PO Box 100, 1475, Budapest, Hungary

    Gyula Simig & Balázs Volk

Authors
  1. Eszter Kókai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. József Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tünde Tóth
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. József Kupai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Péter Huszthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gyula Simig
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Balázs Volk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Balázs Volk.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 1285 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kókai, E., Nagy, J., Tóth, T. et al. Convenient synthesis of 2-substituted 5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-ones. Monatsh Chem 147, 767–773 (2016). https://doi.org/10.1007/s00706-015-1634-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00706-015-1634-1

Keywords

Search

Navigation