g Open Source Malaria Meeting December 20 th 2013 Location: Agenda:

g Amide Synthesis CRO Route A from 6-chloropyrazine-2-carboxylic acid (1) - Joie Garfunkle

g Amide Synthesis CRO Carbonylation Attempts – would allow use of common intermediate

4 Oxidative cyclisation of heteroarylhydrazones  Low yield due to E- selective oxidation with PIDA  Chloramine-T gives cleaner, higher-yielding reaction; 100x cheaper but also E-selective  In-situ isomerisation needed; some precent found but using Pb, Hg, etc ConditionsConv. (NMR)Remaining E Isomer Remaining Z Isomer CRO (PIDA, 1h, rt, DCM)38%ND PIDA, 24h, rt, DCM~50% DMP, 1h, rt, DCM0% DMP, 24h, rt, DCM0% Chloramine-T, 2-MeTHF, 75°C, 1.5h ~50% Chloramine-T, 2-MeTHF, 75°C, 24h ~40%~60% Chloramine-T, 2-MeTHF, 75°C, 1.5h, AcOH (1eq) ~50% Chloramine-T, 2-MeTHF, 75°C, 1.5h, TFA (1eq) ~50%