Two Cycles with One Catch: Hydrazine in Ugi 4-CR and Its Postcyclizations.
Isocyanide-based multicomponent reactions (IMCR) are by far the most versatile reactions that can construct relatively complex molecules by one-pot synthesis. More importantly, the development of post IMCR modifications significantly improves the scaffold's diversity. Here, we describe the use of N-Boc protected hydrazine together with α-amino acid derived isocyanides in the Ugi tetrazole reaction and its post cyclization under both acidic and basic conditions. The cyclization in acidic conditions was conducted in a one pot fashion, which give 7-aminotetrazolopyrazinone (6) and tetrazolotriazepinone (7) cyclic products. The post cyclization under basic condition could selectively afford Boc-protected 7-aminotetrazolopyrazinone (8) products in yield of 38-87%.
University of Groningen , Department of Drug Design, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Yuanze
Y
Wang
University of Groningen , Department of Drug Design, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Pravin
0000-0002-0903-8174
P
Patil
Jagiellonian University , Faculty of Chemistry, Department of Crystal Chemistry and Crystal Physics, Biocrystallography Group, Ingardena 3, 30-060 Krakow, Poland.
Katarzyna
K
Kurpiewska
Jagiellonian University , Faculty of Chemistry, Department of Crystal Chemistry and Crystal Physics, Biocrystallography Group, Ingardena 3, 30-060 Krakow, Poland.
Justyna
J
Kalinowska-Tluscik
University of Groningen , Department of Drug Design, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Alexander
0000-0002-9923-8873
A
Dömling
D020650:Combinatorial Chemistry Techniques; D003486:Cyanides / Q000138:chemical synthesis / Q000737:chemistry*; D003500:Cyclization; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry
C482960:3-aminopyrazinone; D003486:Cyanides; D006834:Hydrazines; D011719:Pyrazines; D013777:Tetrazoles
European Lead Factory; hydrazine; isocyanide-based multicomponent reactions; one-pot synthesis; post cyclization; scaffolds diversity; tetrazole