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28th March 2014 @ 00:48

GitHub Tag #168

Introduction

In September 2013, the OSM team announced a new series, the triazolopyrazines. The team looked at the data provided by MMV (from Big Pharma and the CRO) and started to plan the next amides to synthesise. Currently, the OSM lab in Sydney are targetting ether and amide compounds based on actives from the original set. Several amides were made as part of the original pre-OSM campaign.

The amides

Two amide compounds (AEW 120-2 GitHub Tag #156 and TM 9-1 GitHub Tag #152) have been successfull synthesised and now the team need to choose some further amides to synthesise.

Inga perfomed a search of commercially available primary and secondary anilines and benzylamines and the team ordered some representative compounds. There is also the opportunity to introduce different aryl groups on the right hand side of the molecule through the use of different aldehyde in the synthesis. The figure below indicates compounds that can be accessed in Sydney with the materials currently available.

CLogP Data has been calculated for some of these compounds and can be found in the ChemDraw or PNG files.

Possible amides CLogP.cdxml
Possible amides CLogP.png

Consultation

Which compounds should be synthesised based on the starting materals currently in the lab? Do any of the compounds above look particularly attractive/unattractive. If you can help the team to decide on further amine or aldehyde (to introduce Ar) starting materials then we'd love to hear your thoughts. Commercially available compounds are preferrable but of course we can make some amines/aldehydes if they look interesting.

Ideas/suggestions can be posted as comments below this blog, on GitHub, our G+ site, Twitter or last (and also least) by email to opensourcemalaria@gmail.com.

Thanks

The OSM Team

(Originally authored by Alice Williamson, then tweaked by Mat Todd)

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7th March 2014 @ 01:35

A search in Scifinder was conducted for reaction conditions for the below generic schemes. The purpose of this was to find conditions to conduct a model experiment to create the ether linkage on 2,6-dichloropyrazine before attempting the same reaction with the triazolopyrazine, which we only have in very low yields.

A search for each scheme was performed using the reaction structure search and ticking the ‘substructure’ box. The reactions were filtered by:

  • Yields of 70-100%
  • Journals in English
  • Must have an available experimental procedure.

Promising experiments/conditions for pyrazines:

1. 10.1021/np200386c

Yield of 94%

2. 10.1021/jm061247v

Yield of 83%

Promising experiments/conditions for pyridines:

3. 10.1021/jo800866w

There are several options for the alcohol here, each with different yields.

4. 10.1021/jo901707x

Yields:

90% where Ar = 2-MeO-C6H4 and R = H

92% where Ar = 4-MeO-C6H4 and R = H

96% where Ar = C6H5 and R = Me

75% where Ar = 4-CF3-C6H4 and R = H

93% where Ar = 4-Cl-C6H4 and R = H

 

5. 10.1021/jo0602773

Yield of 95%

I will start by trying the reaction from reference 4, but using 2,6-dichloropyrazine instead of the 2-chloropyradine as it is closer to the triazolopyrazine. I will also use phenethyl alcohol (HO(CH2)2C6H5) as this is closest to the ether I will eventually use to link to the triazolopyrazine. I will also attempt this reaction using 2,6-dichloropyrazine and the 4-MeO-C6H4 alcohol listed above as a comparison. Next week I will try the reactions from references 1 and 2 as their reaction times are longer than what I can achieve this afternoon.

Attached Files