Nugget of niceness
So for the first time in a while a little chemistry - this is from Hofmann-La Roche and their CB-1 inverse agonist paper (DOI) in JMC. Over on In the Pipeline there has been a fair bit of chatter on whether this whole target class is eternally doomed folloing the Rimonabant disaster - I remain thoroughly agnostic on the matter due to profound ignorance. That aside, I like this neat little preparation of the 1,1-dichlorides.
Not something I have seen before, and always nice to see some of the med chem rules getting ignored (no acetals!).
I like also the preparation of the 1,1-dichloride with thionyl chloride, but i prefer the double Friedel-Craft reaction with CCl4 .
And excuse me for my “profound ignorance” but why no acetals, i guess because of the aldehydes…but what is the main target or the main problem with this type of compounds.
Comment by caustic — April 16, 2008 @ 8:27 pm
I have always found diaryl ketals to be very stable to a wide variety conditions. The catachol would probably add stability due to the formation of a nice rigid 5-membered ring.
Comment by milo — April 19, 2008 @ 10:14 pm
Compound 12a, anyone see the error?
Comment by know what amine? — April 24, 2008 @ 8:02 pm
Dimethyl or in general dialkyl acetals are certainly not preferred and in general avoided.
Ketals should be better, but you don’t see them much either.
However, this is a methylenedioxobenzene, which is even further stabilized by the aryl groups.
The methylenedioxobenzene and also ethylenedioxobenzene is a common med. chem. feature, which is accepted. E.g. seen in GSK’s Paroxetine (Paxil, Seroxat).
I hope this was of some help to you.
Comment by Zybermus — May 6, 2008 @ 8:55 pm