Cook–Heilbron thiazole synthesis

[2] This reaction was first discovered in 1947 by Alan H. Cook, Sir Ian Heilbron, and A.L Levy, and marks one of the first examples of 5-aminothiazole synthesis with significant yield and diversity in scope.

[2] In recent years, modifications of the Hantzsch thiazole synthesis are the most common, partly because of its ease in introducing R- group diversity.

However, in 2008 Scott et al. employed a Cook-Heilbron synthesis in their approach to synthesize novel of pyridyl and thiazolyl bisamide CSF-1R inhibitors for use in novel cancer therapeutics.

For instance, 2-methyl-5-aminothiazoles were prepared via condensation and cyclization of aminoacetonitrile and ethyldithioacetate as part of the synthesis of thiazolyl bisamines:[9] Thiazoles are essential components of many biologically active compounds making them important features in drug design.

[10] Consequently, understanding and applying a range of approaches to synthesize thiazoles facilitates greater flexibility in both designing drugs as well as optimizing synthetic routes.

Priority system of numbering thiazole positions.
The mechanism for the Cook-Heilbron synthesis of a 5-aminothiazole starting from an a-aminonitrile and carbon disulphide. An adaptation of the mechanism proposed in Li, J. (2004). Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications.
The mechanism for the Cook-Heilbron synthesis of a 5-aminothiazole starting from an a-aminonitrile and carbon disulphide. An adaptation of the mechanism proposed in Li, J. (2004). Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications.
An example of an application of the Cook-Heilbron thiazole synthesis. Illustrates the synthesis of 2-methyl-5-aminothiazoles were prepared via condensation and cyclization of aminoacetonitrile and ethyldithioacetate as part of an approach to synthesize pyridyl and thiazoyl bisamide CSF-1R inhibitors for use in novel cancer therapeutics. Adapted from study by 12. Scott et al. (2008). Pyridyl and thiazolyl bisamide CSF-1R inhibitors for the treatment of cancer. Bioorganic & Medicinal Chemistry Letters, 18(17), pp.4794-4797.
An example of an application of the Cook-Heilbron thiazole synthesis. Illustrates the synthesis of 2-methyl-5-aminothiazoles were prepared via condensation and cyclization of aminoacetonitrile and ethyldithioacetate as part of an approach to synthesize pyridyl and thiazoyl bisamide CSF-1R inhibitors for use in novel cancer therapeutics. Adapted from study by 12. Scott et al. (2008). Pyridyl and thiazolyl bisamide CSF-1R inhibitors for the treatment of cancer. Bioorganic & Medicinal Chemistry Letters, 18(17), pp.4794-4797.