[marinelson]

I am forming methyl-2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carboxylate from methyl formate, NaOMe, methyl chloroacetate and 2,4-diamino-6-hydroxypyrimidine. NMR indicates this is successful. I am then hydrolysing with NaOH in H2O:DMSO, and NMR was inconclusive. It is not soluble in anything apart from boiling water. Do I need to neutralise the product, as I assume I am forming the sodium salt? 

[wildfyr]

Do us all a favor and draw the reaction out in line form chemdraw or another similar program please

[marinelson]

Sorry

[sjb]

I would imagine that you would need careful pH control, as you also need to take care of the amine and this looks weakly zwitterionic to me. Is there literature precedent for your hydrolysis step? What is the next step?

[marinelson]

Method is in the paper attached. There isn't a next step, I need the carboxylic acid as a substrate for enzyme assays.

[wildfyr]

I agree that you probably have made the Na+ salt. Titrating it back to neutral without protonating those amines is pretty annoying... you could try rinsing it with very dilute acetic acid. So youre sitting at pH 5-6 or so.

FTIR should be able to tell you if you have a carboxylate or a carboxylic acid (carboxylate is around 1600, carboxylic acid is like 1710).

How did you get NMR if its only soluble in boiling H20?

[sjb]

It may not seem like much, but I note from the SI you have posted that the solvent mix is different to what you have drawn out. Also, it's not clear but I think the concentration of NaOH may be different as well (is the 50 mM the overall concentration in what you have drawn out, or the concentration of what you have added?)

[marinelson]

The product was partially soluble in DMSO so was able to get NMR, but not soluble in anything to get mass spec.

[Babcock_Hall]

Sometimes using an organic base (triethylamine or tributylamine) to remove a proton and serve as the counter-ion to the carboxylate group can improve the solubility in an organic solvent.  I have no experience with this class of compounds, however.

Can someone enlighten me as to what is happening in the first step?

[hypervalent_iodine]

The product was partially soluble in DMSO so was able to get NMR, but not soluble in anything to get mass spec.

For your MS, have you tried dissolving it in THF? I work with a number of somewhat similar pyrimidines that show very poor solubility, and find that dissolving in THF (followed by a 1:1000 dilution in MeOH) to work quite well. You will possibly need to sonicate the solution. Note also that distilled THF is best for this, otherwise you'll see a lot of crap in the MS.

[sjb]

Can someone enlighten me as to what is happening in the first step?

Deprotonation of methyl chloroacetate by methoxide then addition of methyl formate (crossed Claisen).