Taking Over Synthesis of "The 6 or 8" - Haverford College Superlab Q2

[AronSchwartzHC]

Jessica Koshinski I will be taking over "The Synthesis of The 6 and The 8" in Quarter 2 Superlab at Haverford College. The original synthesis is found here [#402]. The previous group [#429] ran into some trouble with the synthesis of 3,5-dichloro-2-methylpyrazine. As a result, we have altered the first step of the synthesis.

We will be recording our work in this lab notebook: "http://malaria.ourexperiment.org/haverford_college_s".

[mattodd]

Hi @AronSchwartzHC - welcome aboard! Could you please take a look at these comments I wrote on another Issue, concerning this "hand-over" phase? Important that we have Issues here that can be closed at some point, and that we're clear which reactions you're going to be doing, and which reactions you're talking about.

[mattodd]

Another quick clarification if you wouldn't mind, @AronSchwartzHC @rbroadrup-HC - is the target here the "6" (which is in the picture) or the "8" (which is in the links) or is it actually both?

[AronSchwartzHC]

@mattodd, @rbroadrup-HC We are unsure whether it will be the 6 or 8 the depending on the addition of the hydrazine to the dichloro compound. Right now we are only showing the synthesis of the 6 in the picture.

[mattodd]

Hopefully you got something interesting out of the chlorination reaction you did most recently? Just a note on reaction numbering - can you give each reaction a unique code of the kind I referred to, and use that somewhere in your ELN posts, otherwise we quickly get lost in trying to follow your work. Also, each ELN entry needs a title, so that we can link to it. You'll notice that you can't easily find the URL for your most recent entry because of this...

[AronSchwartzHC]

We are to run the column today. I think I just corrected everything I added the title- a unique code to each of our reactions number and smiles to the ELN entries that are under my name. I will tell Jessica to do the same today.

[AronSchwartzHC]

We were unsuccessful in making 3-5-dichloro-2-methylpyrazine. Instead, we are buying it and it should be here at Haverford soon.

[mattodd]

Great, @AronSchwartzHC please do keep us posted. Looks good.

[AronSchwartzHC]

End of Semester report from Aron Schwartz and Jessica Koshinski

One or both of the molecules above have been synthesized (0.4g). Note that we did buy the 3-5-dichloro-2-methylpyrazine. We also tried the reaction below to see if we would get the amide to add to a specific chlorine as shown below. We will update you on this reaction hopefully this weekend.

[AronSchwartzHC]

We are having a bit of difficulty with the following reaction. Any ideas would be appreciated. Smiles: ClC1=C(C)N=CC2=NN=C(C3=CC=C(OC(F)F)C=C3)N21

The reaction was run at room temperature with equal molar equivalents of reagent to ring closing agent. The reaction was then run a second time at higher temperature (35˚C) and a 3:1 molar ratio of ring closing agent to starting material. Protocols can be see here: http://malaria.ourexperiment.org/haverford_college_s References to (HASJK-2-10) and (HASJK-2-11).

What about running the reaction in toluene at higher temperature?

Thanks, Aron

[MedChemProf]

@AronSchwartzHC From what I could see in the 1H NMR of the product from your experiment HASJK-2-9, it appears that you did not isolate the product hydrazone. I suggest that you re-inspect the identity of your starting material prior to modifying the ring closure reaction conditions.

[AronSchwartzHC]

Haverford College will not continue with the synthesis of the 6 or the 8. The starting material, 3,5-dichloro-2-methylpyrazine, is too expensive to repurchase.