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Synthesis 2021; 53(14): 2457-2468
DOI: 10.1055/a-1401-2795
paper

A New One-Pot Three-Component Synthesis of 4-Aryl-6-cycloamino-1,3,5-triazin-2-amines under Microwave Irradiation

Muhammad Syafiq Bin Shahari
a   School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia
,
Ahmad Junaid
b   Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA
,
Edward R. T. Tiekink
c   Research Centre for Crystalline Materials, School of Medical and Life Sciences, Sunway University, 5 Jalan Universiti, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia
,
Anton V. Dolzhenko  ∗
a   School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor Darul Ehsan 47500, Malaysia
d   School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, GPO Box U1987 Perth, Western Australia 6845, Australia
› Author AffiliationsThis work is supported by the Ministry of Higher Education, Malaysia under Fundamental Research Grant Scheme (Grant no. FRGS/1/2020/STG04/MUSM/02/2). This work also received partial support from the School of Pharmacy, Monash University Malaysia (Bridging Grant 2020). Sunway University Sdn Bhd is thanked for the financial support of the X-ray crystallography laboratory (Grant no. STR-RCTR-RCCM-001-2019).
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Dedicated to the memory of Professor Boris Syropyatov (6 Nov 1940 – 24 Oct 2020)

Abstract

A new method for the fast synthesis of diverse 4-aryl-6-cycloamino-1,3,5-triazin-2-amines was developed. The synthesis is performed under microwave irradiation in a one-pot manner from cyanoguanidine, aromatic aldehydes, and cyclic amines. Their three-component reaction in the presence of hydrochloric acid produced dihydrotriazines, which were then converted (without isolation) into the targeted compounds via aromatic dehydrogenation in the presence of alkali. The reaction tolerated various aromatic aldehydes (including heterocyclic) and cyclic amines. Crystal structures of two representative 4-aryl-6-morpholino-1,3,5-triazin-2-amines were established by X-ray crystallography. The results of preliminary biological screening identified potent antileukemic activity for 6-[3,4-dihydroisoquinolin-2(1H)-yl]-4-phenyl-1,3,5-triazin-2-amine.

Key words

triazines - multicomponent reactions - microwave-assisted synthesis - dehydrogenative aromatization - antiproliferative activity

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1401-2795.
  • Supporting Information


Publication History

Received: 14 January 2021

Accepted after revision: 26 February 2021

Accepted Manuscript online:
26 February 2021

Article published online:
10 March 2021

© 2021. Thieme. All rights reserved

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