[GinaTageldin]

Hi
I have Dichloro pyrimidine derivative and want to react it with different arylamines ? i tried the reaction in Dioxane/TEA and it didn't work. any suggestions???

[rolnor]

Mabey reflux in DMF with catalytic NaI?

[GinaTageldin]

could i substitute NaI with KI?

[rolnor]

Yes

[sjb]

Possibly, yes.

Which dichloropyrimidine are you trying to aminate, which aryl amine, and (if appropriate) which regioisomer? Usually these seem fairly facile in my experience

[hypervalent_iodine]

Are you hoping to get the monoamine or diamine? Reflux in THF with between 1-2 equivalents of DMAP overnight has always been my go to with these substrates. You may get competing reactions depending on your substitution pattern however, so you might need to play with conditions and the way you perform the addition of A to B. Do you have anything in the 2-position?

[clarkstill]

You could try a Buchwald coupling too?

[GinaTageldin]

Possibly, yes.

Which dichloropyrimidine are you trying to aminate, which aryl amine, and (if appropriate) which regioisomer? Usually these seem fairly facile in my experience

4,6-dichloropyrimidin-2-amine,
substituted phenylene diamines
i think 4,6-dichloropyrimidin-2-amine has a plane of symmetry across the amino group so,  attack on cl in both position is equivalent!!!!

[GinaTageldin]

Are you hoping to get the monoamine or diamine? Reflux in THF with between 1-2 equivalents of DMAP overnight has always been my go to with these substrates. You may get competing reactions depending on your substitution pattern however, so you might need to play with conditions and the way you perform the addition of A to B. Do you have anything in the 2-position?

4,6-dichloropyrimidin-2-amine
yes position 2 is an amino group, i need only a monoamine
could you specify the condition using DMAP condition?
Thank you

[GinaTageldin]

Yes

Thank you Sir

[GinaTageldin]

You could try a Buchwald coupling too?

Actually, its conditions are not available in my lab.

[hypervalent_iodine]

Ah. I have worked with that compound before. It's a bit of an oddity out of the 2-amino pyrimidines I've dealt with to be honest. I always had way more issues with it. Your biggest problem is going to be reaction of the pyrimidine with itself and generally over amination. Not going to be an easy thing to do I'm afraid.

Order of addition, temp, base strength and reaction time will be absolutely crucial. Pre-treat your amine (not the pyrimidine) with base (1 eq exactly) - I would use pyridine. Then add it in slowly to a solution of your pyrimidine in THF at room temp. You might struggle with TLC'ing it to monitor progress, so I would use GCMS if you can. You only need a short run (I'd use something that goes up to 230oC with a max run time of 12 minutes). I wouldn't let the reaction go longer than 2 hours to start with.

[sjb]

i think 4,6-dichloropyrimidin-2-amine has a plane of symmetry across the amino group so,  attack on cl in both position is equivalent!!!!

That it does - hence why I was checking on your precise compound. 2,4-dichloropyrimidine for instance does not have this symmetry.

[rolnor]

Maybe procect the aminopyrimidine with a Boc-group or make the aminogroup into a azido-group via diazotation that after coupling can be reduced easily?

[hypervalent_iodine]

Making the reaction dilute might also be an solution to avoiding self-reaction.