The use of CDMT as a coupling agent has been investigated fairly extensively, and it demonstrates several advantages over other coupling agents. It is a stable, crystalline compound, with good solubility in organic solvents, and is commercially available in large quantities.
White to off-white crystalline powder
Store in a cool and dry place (2-8oC)
- The standard method for making amides using CDMT is to activate the acid using CDMT and a base such as N-methylmorpholine. This generates an active ester which is subsequently reacted with the amine coupling partner in the same pot. The reaction typically proceeds to completion in a matter of 8–14 h. This method is effective for the formation of a variety of compounds, including esters and Weinreb amides. Workup of the products is typically afforded by extraction with dilute acid, as the CDMT and its triazine by-products are typically weakly basic and easily removed extractively.
- When the product is a nonwater soluble solid, the reaction can be run in acetonitrile and many of the products isolated simply by adding water and recovering the precipitate.
- CDMT is a reagent which has been used mainly in SPPS. In the presence of N-methylmorpholine (NMM) as base, the reagent gives low levels of racemization.
- Numerous oligopeptides of 3-heteroaryloamino-2,3-dehydroalanine have been obtained using CDMTas the coupling reagent.
- In the pure state CDMT is stable almost indefinitely (20 years in the author’s laboratory) without any traces of decomposition (Kamin´ ski, 1996).
- Recent development in peptide coupling reagents
T. I. Al-Warhi, H. M.A. Al-Hazimi, and A. El-Faham Journal of Saudi Chemical Society, 2012, 16, 97–116.
- A novel generation of coupling reagents. Enantiodifferentiating coupling reagents prepared in situ from 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and chiral tertiary amines
Z. J. Kamiński, B. Kolesińska, J. E. Kamińska, and J. Góra J. Org. Chem., 2001, 66, 6276-6281.
- New observations on peptide bond formation using CDMT
C. E. Garrett, X.g Jiang, K. Prasad, and O. Repic Tetrahedron Lett., 2002, 43, 4161–4165.
- CDMT at e-EROS: Encyclopedia of Reagents for Organic Synthesis.