[Jessica2015]

Dear all,
 
I would like to immobilize small molecules by click-chemistry for protein binding asays.
Does anyone of you have an idea how to introduce alkyne or azide groups into such a molecule (image attached)?
I tried the Mannich reaction on a DADPA resin, but the result wasn't satisfacory or at least hard to find very helpful.
 
Any help much appreciated

[TheUnassuming]

It depends on where you need the functionality.  Generally you would introduce the handle earlier in the synthesis.
Do you have any idea of how the protein is binding the compound shown?  If you know what part is exposed to solvent (assuming it has one) you would then put the azide/alkyne in that area.  To get the protein to engage the small molecule you also might have to put a spacer between your compound and the clickable functionality.

[Jessica2015]

I would like to keep the left half of the molecule free (the NH would be my border), since I have some hints that the functionality doesn't come from the right part of the molecule (as depicted). Other hints point to reduced functionality if a bulky modification is very closely linked to the NH group. How would you couple it?
Thanks so much!

[Dan]

I tried the Mannich reaction on a DADPA resin, but the result wasn't satisfacory or at least hard to find very helpful.

I might be missing something, but I don't think the molecule you posted contains any of the functional groups required for a Mannich reaction.

I think you might have to install the linker handle earlier in the synthesis. Electrophilic aromatic substitution might be a viable way to install a handle on the aniline ring, but the furan will probably also participate giving you complex mixtures to purify.

How do you make the inhibitor?

[Jessica2015]

Ref. to Mannich reaction: You're right, the molecule doesn't have an active hydrogen - I'm puzzled how I ended up trying the coupling...

The compound is part of a big library, we don't do the synthesis, it's done by a company.
Is there any way to restrict the reaction in favor of the electrophilic substitution at the aniline ring?

[TheUnassuming]

The compound is part of a big library, we don't do the synthesis, it's done by a company.
Is there any way to restrict the reaction in favor of the electrophilic substitution at the aniline ring?

Not that I can think of no.  EAS is relatively harsh in most cases and your alpha-amide oxazole and furan ring system is almost certainly going to react first.