Post on 01-Jan-2016
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Open Source Malaria Meeting
December 20th 2013
Location: http://webconf.ucc.usyd.edu.au/osmdec20/Agenda: http://malaria.ourexperiment.org/uri/48f
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Amide SynthesisCRO Route A from 6-chloropyrazine-2-carboxylic acid (1) - Joie Garfunkle
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Amide SynthesisCRO 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
N
N
Cl
NN
CN
N
N
Cl
NH
N
CN
Oxidative
Conditions
N
N
Cl
NH
N
CN
(E)
(Z) + N
N
Cl
NH
N
CN
(Z)+
Conditions Conv. (NMR) Remaining E Isomer
Remaining Z Isomer
CRO (PIDA, 1h, rt, DCM) 38% ND ND
PIDA, 24h, rt, DCM ~50% ~50%
DMP, 1h, rt, DCM 0% 0% 0%
DMP, 24h, rt, DCM 0% 0% 0%
Chloramine-T, 2-MeTHF, 75°C, 1.5h
~50% ~50%
Chloramine-T, 2-MeTHF, 75°C, 24h
~40% ~60%
Chloramine-T, 2-MeTHF, 75°C, 1.5h, AcOH (1eq)
~50% ~50%
Chloramine-T, 2-MeTHF, 75°C, 1.5h, TFA (1eq)
~50% ~50%