The study of the interaction of 4,6-dichloropyrimidine-5-carbaldehyde with glycine esters

Authors

  • H. M. Zinchenko Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • L. V. Muzychka Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • I. I. Biletskiy Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • O. B. Smolii Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.18.935

Keywords:

4, 6-dichloropyrimidine-5-carbaldehyde, pyrido[2, 3-d]pyrimidin-7-one, pyrrolo[2, 3-d]pyrimidines, cyclization

Abstract

Aim. To study the interaction of 4,6-dichloropyrimidine-5-carbaldehyde with methyl- and with tert-butylglycinate depending on the reaction conditions.
Results and discussion. It has been found that the reaction of 4,6-dichloro-5-formylpyrimidine with hydrochlorides of glycine esters in the presence of triethylamine leads to obtaining derivatives of N-(5-formylpyrimidin-4-yl)glycinate and cyclization products: pyrrolo[2,3-d]pyrimidine and pyrido[2,3-d]pyrimidine.
Experimental part. The interaction of 4,6-dichloropyrimidine-5-carbaldehyde with methyl or tert-butyl glycinate in methanol in the presence of triethylamine depending on the molar ratio gives the mixture of 5-hydroxy-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine and 6-amino-4-chloro-7-oxopyrido[2,3-d]pyrimidine-8(7H)-yl)acetate.
The composition and structure of the compounds synthesized have been confirmed by NMR-spectroscopy, chromatography mass-spectrometry and elemental analysis.
Conclusions. The previously unknown derivatives of pyrrolo[2,3-d]pyrimidine and pyrido[2,3-d]pyrimidine have been obtained as a result of the interaction of 4,6-dichloro-5-formylpyrimidine with methyl and tert-butylglycinate.
The reaction features depending on the reactants ratio have been studied. The prospects for the synthesis of potential biologically active compounds from 6-amino-4-chloro-7-oxopyrido[2,3-d]pyrimidine-8(7H)-yl)acetate have been described.

Downloads

Download data is not yet available.

References

  1. Morrill, C., Babu, S., Almstead, N. G., Moon. Y.–C. (2013). Synthesis of 1,4–disubstituted pyrazolo[3,4–d]pyrimidines from 4,6–dichloropyrimidine–5–carboxaldehyde: Insights into selectivity and reactivity. Synthesis, 45 (13), 1791–1806. doi: 10.1055/s–0033–1338862
  2. Wang, H., Zhang, Y., Ye, W., Schneller, S. W. (2014). Preparation of 8–Aza–7–deazaaristeromycin and –neplanocin A and Their 5′–Homologs. Journal of Heterocyclic Chemistry, 52 (4), 1132–1135. doi: 10.1002/jhet.2137
  3. Babu, S., Morrill, C., Almstead, N. G., Moon, Y.–C. (2013). Selective Synthesis of 1–Substituted 4–Chloropyrazolo[3,4–d]pyrimidines. Organic Letters, 15 (8), 1882–1885. doi: 10.1021/ol4005382
  4. Fu, Y., Wang, Y., Wan, S., Li, Z., Wang, G., Zhang, J., Wu, X. (2017). Bisarylureas Based on 1H–Pyrazolo[3,4–d]pyrimidine Scaffold as Novel Pan–RAF Inhibitors with Potent Anti–Proliferative Activities: Structure–Based Design, Synthesis, Biological Evaluation and Molecular Modelling Studies. Molecules, 22 (4), 542. doi: 10.3390/molecules22040542
  5. Deng, X., Okram, B., Ding, Q., Zhang, J., Choi, Y., Adrián, F. J., Gray, N. S. (2010). Expanding the Diversity of Allosteric Bcr–Abl Inhibitors. Journal of Medicinal Chemistry, 53 (19), 6934–6946. doi: 10.1021/jm100555f
  6. Lawhorn, B. G., Philp, J., Zhao, Y., Louer, C., Hammond, M., Cheung, M., Kallander, L. S. (2015). Identification of Purines and 7–Deazapurines as Potent and Selective Type I Inhibitors of Troponin I–Interacting Kinase (TNNI3K). Journal of Medicinal Chemistry, 58 (18), 7431–7448. doi: 10.1021/acs.jmedchem.5b00931
  7. Wang, T., Liu, X., Hao, M., Qiao, J., Ju, C., Xue, L., Zhang, C. (2016). Design, synthesis and evaluation of pyrrolo[2,3– d ]pyrimidine–phenylamide hybrids as potent Janus kinase 2 inhibitors. Bioorganic & Medicinal Chemistry Letters, 26 (12), 2936–2941. doi: 10.1016/j.bmcl.2016.04.027
  8. Yang, H.–Z., Pan, M.–Y., Jiang, D.–W., He, Y. (2011). Synthesis of Janus type nucleoside analogues and their preliminary bioactivity. Organic & Biomolecular Chemistry, 9 (5), 1516. doi: 10.1039/c0ob00495b
  9. Kawakita, Y., Seto, M., Ohashi, T., Tamura, T., Yusa, T., Miki, H., Ishikawa, T. (2013). Design and synthesis of novel pyrimido[4,5– b ]azepine derivatives as HER2/EGFR dual inhibitors. Bioorganic & Medicinal Chemistry, 21 (8), 2250–2261. doi: 10.1016/j.bmc.2013.02.014
  10. Verves, E. V., Kucher, A. V., Muzychka, L. V., Smolii, O. B. (2013). Synthesis of 7–alkyl–4–amino–7H–pyrrolo–[2,3–d]pyrimidine–6–carboxylic acids. Chemistry of Heterocyclic Compounds, 48 (12), 1844–1852. doi: 10.1007/s10593–013–1218–0
  11. Zinchenko, A. N., Muzychka, L. V., Biletskii, I. I., Smolii, O. B. (2017). Synthesis of new 4–amino–substituted 7–iminopyrido[2,3–d]pyrimidines. Chemistry of Heterocyclic Compounds, 53 (5), 589–596. doi: 10.1007/s10593–017–2096–7
  12. Xiang, J., Wen, D., Xie, H., Dang, Q., Bai, X. (2010). Synthesis of Novel 8,9–Dihydro–5H–pyrimido[4,5–e][1,4]diazepin–7(6H)–ones. Journal of Combinatorial Chemistry, 12 (4), 503–509. doi: 10.1021/cc100039w
  13. Lavecchia, M. J., Puig de la Bellacasa, R., Borrell, J. I., Cavasotto, C. N. (2016). Investigating molecular dynamics–guided lead optimization of EGFR inhibitors. Bioorganic & Medicinal Chemistry, 24 (4), 768–778. doi: 10.1016/j.bmc.2015.12.046
  14. Wurz, R. P., Pettus, L. H., Ashton, K., Brown, J., Chen, J. J., Herberich, B., Tasker, A. S. (2015). Oxopyrido[2,3–d]pyrimidines as Covalent L858R/ T790M Mutant Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors. ACS Medicinal Chemistry Letters, 6 (9), 987–992. doi: 10.1021/acsmedchemlett.5b00193
  15. Xu, T., Peng, T., Ren, X., Zhang, L., Yu, L., Luo, J., Ding, K. (2015). C5–substituted pyrido[2,3–d]pyrimidin–7–ones as highly specific kinase inhibitors targeting the clinical resistance–related EGFRT790M mutant. MedChemComm, 6 (9), 1693–1697. doi: 10.1039/c5md00208g
  16. Yu, L., Huang, M., Xu, T., Tong, L., Yan, X., Zhang, Z., Lu, X. (2017). A structure–guided optimization of pyrido[2,3– d ]pyrimidin–7–ones as selective inhibitors of EGFR L858R/T790M mutant with improved pharmacokinetic properties. European Journal of Medicinal Chemistry, 126, 1107–1117. doi: 10.1016/j.ejmech.2016.12.006
  17. Toogood, P. L., Harvey, P. J., Repine, J. T., Sheehan, D. J., VanderWel, S. N., Zhou, H., Fry, D. W. (2005). Discovery of a Potent and Selective Inhibitor of Cyclin–Dependent Kinase 4/6. Journal of Medicinal Chemistry, 48 (7), 2388–2406. doi: 10.1021/jm049354h
  18. Reddy, M. V. R., Akula, B., Cosenza, S. C., Athuluridivakar, S., Mallireddigari, M. R., Pallela, V. R., Reddy, E. P. (2014). Discovery of 8–Cyclopentyl–2–[4–(4–methyl–piperazin–1–yl)–phenylamino]–7–oxo–7,8–dihydro–pyrido[2,3–d]pyrimidine–6–carbonitrile (7x) as a Potent Inhibitor of Cyclin–Dependent Kinase 4 (CDK4) and AMPK–Related Kinase 5 (ARK5). Journal of Medicinal Chemistry, 57 (3), 578–599. doi: 10.1021/jm401073p
  19. Rudolph, J., Murray, L. J., Ndubaku, C. O., O’Brien, T., Blackwood, E., Wang, W., Zhong, Y. (2016). Chemically Diverse Group I p21–Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window. Journal of Medicinal Chemistry, 59 (11), 5520–5541. doi: 10.1021/acs.jmedchem.6b00638
  20. Camarasa, M., Puig de la Bellacasa, R., González, À. L., Ondoño, R., Estrada, R., Franco, S., Borrell, J. I. (2016). Design, synthesis and biological evaluation of pyrido[2,3–d]pyrimidin–7–(8H)–ones as HCV inhibitors. European Journal of Medicinal Chemistry, 115, 463–483. doi: 10.1016/j. ejmech.2016.03.055
  21. Simon–Szabó, L., Kokas, M., Greff, Z., Boros, S., Bánhegyi, P., Zsákai, L., Kéri, G. (2016). Novel compounds reducing IRS–1 serine phosphorylation for treatment of diabetes. Bioorganic & Medicinal Chemistry Letters, 26 (2), 424–428. doi: 10.1016/j.bmcl.2015.11.099
  22. Cheng, H., Hoffman, J. E., Le, P. T., Pairish, M., Kania, R., Farrell, W., Rahavendran, S. V. (2013). Structure–based design, SAR analysis and antitumor activity of PI3K/mTOR dual inhibitors from 4–methylpyridopyrimidinone series. Bioorganic & Medicinal Chemistry Letters, 23 (9), 2787–2792. doi: 10.1016/j.bmcl.2013.02.020
  23. Puig de la Bellacasa, R., Roué, G., Balsas, P., Pérez–Galán, P., Teixidó, J., Colomer, D., Borrell, J. I. (2014). 4–Amino–2–arylamino–6–(2,6–dichlorophenyl)– pyrido[2,3–d]pyrimidin–7–(8H)–ones as BCR kinase inhibitors for B lymphoid malignancies. European Journal of Medicinal Chemistry, 86, 664–675. doi: 10.1016/j.ejmech.2014.09.018
  24. Zinchenko, A. N., Muzychka, L. V., Smolii, O. B., Bdzhola, V. G., Protopopov, M. V., Yarmoluk, S. M. (2017). Synthesis and biological evaluation of novel amino–substituted derivatives of pyrido[2,3–d]pyrimidine as inhibitors of protein kinase CK2. Biopolymers and Cell, 33 (5), 367–378. doi: 10.7124/bc.000960

Downloads

Published

2018-03-14

How to Cite

(1)
Zinchenko, H. M.; Muzychka, L. V.; Biletskiy, I. I.; Smolii, O. B. The Study of the Interaction of 4,6-Dichloropyrimidine-5-Carbaldehyde With Glycine Esters. J. Org. Pharm. Chem. 2018, 16, 42-48.

Issue

Vol. 16 No. 1(61) (2018)

Section

Original Researches

License

Copyright (c) 2018 National University of Pharmacy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors publishing their works in the Journal of Organic and Pharmaceutical Chemistry agree with the following terms:

1. Authors retain copyright and grant the journal the right of the first publication of the work under Creative Commons Attribution License allowing everyone to distribute and re-use the published material if proper citation of the original publication is given.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book) providing proper citation of the original publication.

3. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on authors’ personal websites) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).