Hulme, C., Xu, Z., De Moliner, F., Cappelli, A. P., & Hulme, C. -. (2012). Ugi/aldol sequence: expeditious entry to several families of densely substituted nitrogen heterocycles. Angewandte Chemie (International ed. in English), 51(32).
Martinez-Ariza, G., Ayaz, M., Medda, F., & Hulme, C. (2014). Synthesis of diverse nitrogen-enriched heterocyclic scaffolds using a suite of tunable one-pot multicomponent reactions. The Journal of organic chemistry, 79(11), 5153-62.
Five elegant and switchable three-component reactions which enable access to a new series of nitrogen-containing heterocycles are reported. A novel one-step addition of an isocyanide to a hydrazine derived Schiff base affords unique six-membered pyridotriazine scaffolds (A and E). With slight modification of reaction conditions and replacement of the nucleophilic isocyanide moiety with different electrophiles (i.e., isocyanates, isothiocyanates, cyclic anhydrides, and acyl chlorides) five-membered triazolopyridine scaffolds (B, D, F, G) are generated in a single step. Furthermore, the use of phenyl hydrazine enables access to dihydroindazole-carboxamides, devoid of a bridge-head nitrogen (C). All protocols are robust and tolerate a diverse collection of reactants, and as such, it is expected that the new scaffolds and associated chemistry will garner high interest from medicinal chemists involved in either file enhancement or specific target-related drug discovery campaigns.
Hulme, C., Xu, Z., Dietrich, J., Shaw, A. Y., & Hulme, C. -. (2010). Two step syntheses of fused quinoxaline-benzodiazepines and bis-benzodiazepines. Tetrahedron letters, 51(34).
A two-step solution phase synthesis employing a double UDC (Ugi/Deprotect/Cyclize) strategy has been utilized to obtain fused 6,7,6,6-quinoxalinone-benzodiazepines and 6,7,7,6-bis-benzodiazepines. Optimization of the methodology to produce these tetracyclic scaffolds was enabled by microwave irradiation, incorporation of trifluoroethanol as solvent, and the use of the convertible isocyanide, 4-tert-butyl cyclohexen-1-yl isocyanide.
Martinez-Ariza, G., Dietrich, J., Moliner, F. D., & Hulme, C. (2013). A tandem [3+2] cycloaddition-elimination cascade reaction to generate pyrrolo-[3,4-c]pyrrole-1,3-diones. Synlett, 24(14), 1801-1804.
Abstract:
An efficient tandem [3+2] cycloaddition-elimination cascade sequence has been developed enabling assembly of the pharmacologically relevant pyrrolo-[3,4-c]pyrrole-1,3-dione chemotype. The strategy involves simple mixing of readily accessible oxazolin-2-ones and pyrrole-2,5-diones in the presence of base under mild conditions, rendering the title compounds in typically excellent yields. Of note, this route allows for installation of three points of diversity and is ideal for combinatorial applications and parallel synthesis production campaigns. © Georg Thieme Verlag Stuttgart · New York.
Hulme, C., Xu, Z., Shaw, A. Y., Dietrich, J., Cappelli, A. P., Nichol, G., & Hulme, C. -. (2012). Facile, novel two-step syntheses of benzimidazoles, bis-benzimidazoles, and bis-benzimidazole-dihydroquinoxalines. Molecular diversity, 16(1).
Three scaffolds of benzimidazoles, bis-benzimidazoles, and bis-benzimidazole-dihydroquinoxalines were synthesized via Ugi/de-protection/cyclization methodology. Benzimidazole forming ring closure was enabled under microwave irradiation in the presence of 10% TFA/DCE. The methodology demonstrates the utility of 2-(N-Boc-amino)-phenyl-isocyanide for the generation of new molecular diversity.
