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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%