TY - JOUR N1 - This publication is Open Access under the license indicated.This publication is licensed under CC-BY 4.0 . cc licence by licence Copyright © 2020 American Chemical Society SP - 13438 Y1 - 2020/11/06/ TI - tele-Substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials EP - 13452 AV - public JF - The Journal of Organic Chemistry N2 - We have discovered and studied a tele-substitution reaction in a biologically important heterocyclic ring system. Conditions that favor the tele-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base or the use of softer nucleophiles, less polar solvents, and larger halogens on the electrophile. Using results from X-ray crystallographic and isotope labeling experiments, a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the in vivo active antiplasmodium compounds of Series 4 of the Open Source Malaria consortium. VL - 85 UR - https://doi.org/10.1021/acs.joc.0c01045 A1 - Korsik, M A1 - Tse, EG A1 - Smith, DG A1 - Lewis, W A1 - Rutledge, PJ A1 - Todd, MH IS - 21 ID - discovery10114909 KW - Hydrocarbons KW - Substitution reactions KW - Chemical reactions KW - Aromatic compounds KW - Solvents ER -