BUTTERS
1-(3,4-dichlorophenyl)-1-carbomethoxy-2-methylaminopropane
A South Park Character.
I think you did this after you saw my earlier post (
#2130). Here though, I reduced the ester into a primary alcohol to give it a longer metabolism. The alcohol can be derivatized into an ether also. This is the same as occurred already for tesofensine (from dichloropane). Deutsch reports it too for dichlororitalin. The thing you have to understand with cis-dichloropane is that a ring rearragement occurs in tropanes bearing the beta-beta chemistry
viz. RTI-274. Even in piperidines a
cis-trans rearrangement occurs if you attempt to make an ether out of a cis-alcohol (nocaine like piperidines i mean).
Given that the starting esters are made from benzoyl groups, an alternative product would be a Wittig reaction. This occured both for RTI-31 and Nocaine. Reduction of the olefin to the alkyl groups is consistent with high bioactivity and slow metabolism especially for the n-propyl group.
In fact I see they are calling their compound based on ritalin
CTDP-32476.
Xi ZX, Song R, Li X, Lu GY, Peng XQ, He Y, Bi GH, Sheng SP, Yang HJ, Zhang H, Li J, Froimowitz M, Gardner EL. CTDP-32476: A Promising Agonist Therapy for Treatment of Cocaine Addiction. Neuropsychopharmacology. 2017 Feb;42(3):682-694. doi: 10.1038/npp.2016.155. Epub 2016 Aug 18. PMID: 27534265; PMCID: PMC5240176.
Froimowitz M, Taboada R, Poulos ZJ, Rainone DJ, Imler GH, Gardner EL, Kelley CJ. Chiral Resolution of the Enantiomers of the Slow-Onset Dopamine Reuptake Inhibitor CTDP-32476 and Their Activities. ACS Omega. 2023 Sep 18;8(39):35738-35745. doi: 10.1021/acsomega.3c02997. PMID: 37810691; PMCID: PMC10552101.
One last thing I would want to point out is that instead of Wittig reaction from the aldehyde, wouldn't EtMX addition to the nitrile work and then the Wolff-Kishner reduction of the ketone is only an optional step and does not even have to be performed (ala methadone).
pubchem.ncbi.nlm.nih.gov
