Journal of Drug Design and Medicinal Chemistry

| Peer-Reviewed |

Synthesis of 2-Amino-5-(3-chloropropyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (Bischlorinated Deazaguanine)

Received: 09 January 2017    Accepted: 25 January 2017    Published: 18 February 2017
Views:       Downloads:

Share This Article

Abstract

There are many forms of DNA damage which may arise from the modifications DNA bases. Deazaguanine is a modified DNA base which is recognised by DNA repair enzyme, Methylguanine DNA-methyltranferase (MGMT). The synthesis of Bischlorinated deazaguanine was successfully carried out via two different routes. The first route was achieved through the reaction of pyrrolopyrimidine with benzyl(triethyl)ammonium chloride, dry dimethylaniline and freshly distilled phosphoryl chloride in acetonitrile under argon atmosphere. An alternative method was employed toward achieving the Bischolorinated through the debenzoylation of the protected pyrrolopyrimidine with 1 M NaOH at 50°C for 1h followed by double chlorination reaction using phosphoryl chloride alone at 80°C for 1h. Both routes were found to be successful with lower impurities recorded from the second route though it gives a low yield but it was shorter.

DOI 10.11648/j.jddmc.20170301.11
Published in Journal of Drug Design and Medicinal Chemistry (Volume 3, Issue 1, February 2017)
Page(s) 1-4
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Deazaguanine, Phosphoryl Chloride, Alkylation, Pyrrolopyrimidine, Debenzoylation

References
[1] Frei, J. V., Swenson, D. H., Warren, W., and Lawley, P. D (1978) Alkylation of deoxyribonucleic acid in vivo. Biochem. Jour. 174 1031-1044.
[2] Friedman, H. S., McLendon R. E., Kerby, T., Dugan, M., Bigner, S. H (1998) DNA mismatch repair and O6-akylguanine-DNA alkyltranferase analysis and response to Temodal in newly diagonosed miligant glioma. J. Clin. Oncol. 16 3851-3857.
[3] Saul, R. L. and Ames, B. N. (1986) Background levels of DNA damage in the population. Basic life sciences, 38, 529-535.
[4] Kompis, I. M., Islam, K. and Then, R. L. (2005) DNA and RNA synthesis: antifolates. Chem. Rev., 105, 593-620.
[5] Ami, S. and Mark, R. M. (2006) Exploiting the role of O6-Methylguanine-DNA-methyltranferase in cancer therapy. Curr. Opi. Pharm. 6 355-363.
[6] Gerson, S. L. (2002) Clinical relevance of MGMT in the treatment of cancer. J. Clin. Oncol, 20, 2388-2399.
[7] Tong, W. P., Kirk, M. C. and Ludlum, D. B. (1982) Formation of the cross-link 1-[N3-deoxycytidyl),2-[N1-deoxyguanosinyl]ethane in DNA treated with N, N'-bis(2-chloroethyl)-N-nitrosourea. Cancer Res., 42, 3102-3105.
[8] Dovlatyan, V. V., Eliazyan, K. A., Ghazaryan, E. A. and Yengoyan, A. P. (2006) Synthesis of azinylthioureas and their heterocyclisation using alpha-chloroacetoacetic ester. Chem. Heter. Comp., 42, 389-391.
[9] Kabir, A. and Williams, D. M. (2015) Fluoroscence binding assay of atl 1 protein with sima labelled oligonucleotide containing the tricyclic nucleoside analogue of O6-methyl-2’-deoxyguanosine. Ame. Chem. Sci. Jour. 8 (1), 1-7.
[10] Kasturi, R., Arumugam, T., Mathew, S., Jayaram, L., Dastidar, S. K. and Row, T. N. G. (1992) Reaction of 4-cyano-1,3-dihydroxy-5,6,7,8-tetrahydroisoquinolines with vilsmeier reagent: structure and mechanism of formation of [2,7]naphthyridines. Tetrahedron, 48, 6499-6510.
[11] Williams, D. M., Yakovlev, D. Y. and Brown, D. M. (1997) The synthesis of a tricyclic pyrrolopyrimidine related to N6-hydroxyadenine. J. Chem. Soc., Perkin Trans. 1, 1171-1178.
Author Information
  • Department of Pure and Industrial Chemistry, Faculty of Science, Bayero University, Kano, Nigeria

Cite This Article
  • APA Style

    Kabir Abdu. (2017). Synthesis of 2-Amino-5-(3-chloropropyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (Bischlorinated Deazaguanine). Journal of Drug Design and Medicinal Chemistry, 3(1), 1-4. https://doi.org/10.11648/j.jddmc.20170301.11

    Copy | Download

    ACS Style

    Kabir Abdu. Synthesis of 2-Amino-5-(3-chloropropyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (Bischlorinated Deazaguanine). J. Drug Des. Med. Chem. 2017, 3(1), 1-4. doi: 10.11648/j.jddmc.20170301.11

    Copy | Download

    AMA Style

    Kabir Abdu. Synthesis of 2-Amino-5-(3-chloropropyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (Bischlorinated Deazaguanine). J Drug Des Med Chem. 2017;3(1):1-4. doi: 10.11648/j.jddmc.20170301.11

    Copy | Download

  • @article{10.11648/j.jddmc.20170301.11,
      author = {Kabir Abdu},
      title = {Synthesis of 2-Amino-5-(3-chloropropyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (Bischlorinated Deazaguanine)},
      journal = {Journal of Drug Design and Medicinal Chemistry},
      volume = {3},
      number = {1},
      pages = {1-4},
      doi = {10.11648/j.jddmc.20170301.11},
      url = {https://doi.org/10.11648/j.jddmc.20170301.11},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.jddmc.20170301.11},
      abstract = {There are many forms of DNA damage which may arise from the modifications DNA bases. Deazaguanine is a modified DNA base which is recognised by DNA repair enzyme, Methylguanine DNA-methyltranferase (MGMT). The synthesis of Bischlorinated deazaguanine was successfully carried out via two different routes. The first route was achieved through the reaction of pyrrolopyrimidine with benzyl(triethyl)ammonium chloride, dry dimethylaniline and freshly distilled phosphoryl chloride in acetonitrile under argon atmosphere. An alternative method was employed toward achieving the Bischolorinated through the debenzoylation of the protected pyrrolopyrimidine with 1 M NaOH at 50°C for 1h followed by double chlorination reaction using phosphoryl chloride alone at 80°C for 1h. Both routes were found to be successful with lower impurities recorded from the second route though it gives a low yield but it was shorter.},
     year = {2017}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Synthesis of 2-Amino-5-(3-chloropropyl)-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (Bischlorinated Deazaguanine)
    AU  - Kabir Abdu
    Y1  - 2017/02/18
    PY  - 2017
    N1  - https://doi.org/10.11648/j.jddmc.20170301.11
    DO  - 10.11648/j.jddmc.20170301.11
    T2  - Journal of Drug Design and Medicinal Chemistry
    JF  - Journal of Drug Design and Medicinal Chemistry
    JO  - Journal of Drug Design and Medicinal Chemistry
    SP  - 1
    EP  - 4
    PB  - Science Publishing Group
    SN  - 2472-3576
    UR  - https://doi.org/10.11648/j.jddmc.20170301.11
    AB  - There are many forms of DNA damage which may arise from the modifications DNA bases. Deazaguanine is a modified DNA base which is recognised by DNA repair enzyme, Methylguanine DNA-methyltranferase (MGMT). The synthesis of Bischlorinated deazaguanine was successfully carried out via two different routes. The first route was achieved through the reaction of pyrrolopyrimidine with benzyl(triethyl)ammonium chloride, dry dimethylaniline and freshly distilled phosphoryl chloride in acetonitrile under argon atmosphere. An alternative method was employed toward achieving the Bischolorinated through the debenzoylation of the protected pyrrolopyrimidine with 1 M NaOH at 50°C for 1h followed by double chlorination reaction using phosphoryl chloride alone at 80°C for 1h. Both routes were found to be successful with lower impurities recorded from the second route though it gives a low yield but it was shorter.
    VL  - 3
    IS  - 1
    ER  - 

    Copy | Download

  • Sections