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

Kabir Abdu

doi:doi:10.11648/j.jddmc.20170301.11

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

Kabir Abdu

Published in Journal of Drug Design and Medicinal Chemistry (Volume 3, Issue 1)

Received: 9 January 2017 Accepted: 25 January 2017 Published: 18 February 2017

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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.

Published in	Journal of Drug Design and Medicinal Chemistry (Volume 3, Issue 1)
DOI	10.11648/j.jddmc.20170301.11
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), 2017. Published by Science Publishing Group

Keywords

Deazaguanine, Phosphoryl Chloride, Alkylation, Pyrrolopyrimidine, Debenzoylation

References

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[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.

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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

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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

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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

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@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://article.sciencepublishinggroup.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}
}

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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  -

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Author Information

Kabir Abdu

Department of Pure and Industrial Chemistry, Faculty of Science, Bayero University, Kano, Nigeria

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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

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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

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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://article.sciencepublishinggroup.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