Divergent 2-Chloroquinazolin-4(3H)-one Rearrangement: Twisted-Cyclic Guanidine Formation or Ring-Fused N-Acylguanidines via a Domino Process.

Gang Yan, Bereket L Zekarias, Xiaoyu Li, Victor A Jaffett, Ilia A Guzei, Jennifer E Golden

Chemistry (Weinheim an der Bergstrasse, Germany) 2020 Feb 21

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A highly efficient 2-chloroquinazolin-4(3H)-one rearrangement was developed that predictably generates either twisted-cyclic or ring-fused guanidines in a single operation, depending on the presence of a primary versus secondary amine in the accompanying diamine reagent. Exclusive formation of twisted-cyclic guanidines results from pairing 2-chloroquinazolinones with secondary diamines. Use of primary amine-containing diamines permits a domino quinazolinone rearrangement/intramolecular cyclization, gated through (E)-twisted-cyclic guanidines, to afford ring-fused N-acylguanidines. This scalable, structurally tolerant transformation generated 55 guanidines and delivered twisted-cyclic guanidines with robust plasma stability and an abbreviated total synthesis of an antitumor ring-fused guanidine (4 steps, 55 % yield). © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Gang Yan, Bereket L Zekarias, Xiaoyu Li, Victor A Jaffett, Ilia A Guzei, Jennifer E Golden. Divergent 2-Chloroquinazolin-4(3H)-one Rearrangement: Twisted-Cyclic Guanidine Formation or Ring-Fused N-Acylguanidines via a Domino Process. Chemistry (Weinheim an der Bergstrasse, Germany). 2020 Feb 21;26(11):2486-2492