Synthesis of 3-(2-methyl-7-aminothiazolo[4,5-d]pyrimidin-2-yl)-1-methylbenzene-4-sulfonamide

[tpefoley]

It was decided that due to the difficulty of using SO2 in the synthetic route to compound 25 that I intitially proposed, it would be better to focus my efforts on a different compound instead. Patrick mentioned the potential for a doubly methylated compound to be active, due to the axial twist and resulting increase in solubility. I therefore made the following alternative compound 25 instead:

[tpefoley]

The synthesis is analogous to that of TF3-1 (Compound 24) and PT-22 from the ELN. I used the methylated thienopyrimidine core that I'd previously made for the synthesis of TF3-1.

[PatrickThomson]

Hi Tom, the individual experiments should be written up on the electronic lab notebook here as per the guide I linked to in the document I emailed you. The entries here on GitHub are meant more to track the work that's being done on a target molecule.

[tpefoley]

Apologies, I had a feeling this was in the wrong place! I'll make an entry there. Can you delete this?

[PatrickThomson]

The purpose of this post as a whole (track progress towards compound 25) is fine, and the overarching synthetic route is also fine although I'd suggest working on 24 first while we devise an alternative route that doesn't use SO2. As a general philosophy for the project, I'd avoid deleting posts or comments for the reason that if we can't preserve our teething troubles in public view then what confidence is there that we are running our actual science in a truly open manner?

[tpefoley]

Understood. I can't disagree with that philosophy.

[tpefoley]

Amended the original post to reflect this

[mattodd]

Hi Tom - welcome to the OSM community!

Yes, Patrick's right - we post stuff here that can be resolved in a reasonable timeframe. In fact this entry is good as an example of a "Being Synthesised Now" post, so I've added that label. You can close the issue when you've made the molecule. I added you to the "core contributing" team so you ought to be able to add labels etc yourself now.

Up top, when you refer to Molecule 25, can you supply a link to the background post where that molecule is referred to? This just means that people unfamiliar with this series can read the context and get up to speed.

Patrick's right not to delete anything. Good luck with using the lab notebook. Let us know (here, on Twitter, or G+) if any questions about that. Remember when you start posting to the ELN to include everything, and try to include the molecule codes (SMILES, InChI and InChIkey if possible).

[tpefoley]

I've updated my initial two posts to reflect the actual molecule I decided to make, and the synthesis performed. In the end it was decided that making the initial version of Compound 25 (methyl group ortho to the sulfonamide) would both be too difficult to perform (due to the requirement for SO2 gas to make the precusor) and would not be beneficial to the OSM project.

The new compound 25 (TF4-1) was synthesised with a yield of 24mg and sent off for biological testing. Due to the data that just came back for Patrick's compound (https://github.com/OpenSourceMalaria/OSM_To_Do_List/issues/161), it's likely that TF3-1 and TF4-1 won't be active - but at least this'll confirm for definite that the axial twist kills activity!

[mattodd]

Great stuff Tom - make sure all the data are on the lab notebook so that when we come to write this work up we can just slot it into the experimental. Closing now, waiting for bio results.