Substituted Aminorex Series

[Feretile]

BTW note that the p-(pseudo)halogen PEAs increase in potency down the period i.e. -Br > -Cl > -F i.e. the opposite of the aminorex class. That suggests that the (M)AR scaffold only just fits into the receptor. The above paper included analogues with o-F substitution. A reference states that the 3,4-dimethyl derivative isn't very active. The m-TFM analogue is slightly more potent than AR,

Aminorex analogs

Aminorex (5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) and 4-methylaminorex (4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) are psychostimulants that have long been listed in Schedules IV and I of the UN Convention on Psychotropic Substances of 1971. However, ...

www.ncbi.nlm.nih.gov

If I were looking into multiple ring substitutions, I would imagine that the 2,5-dimethoxy (if a TFM fits, an -OCH3 will likely do so) 4-F. This MAY lend 5HT2a affinity.

If you are looking for something like MDMA (but better), you are going to have to find a substitution that increases serotonin activity, a second one that acts like plain AR but has a duration similar to the p-Me. I'm sure those of you who have studied things like fenfluramine will realise that it's the bulk rather than the electronic character that matters.

Of course, their are some entirely new scaffolds that are currently being considered as drugs of abuse i.e. become schedule 1 in the USA.

 

[unodelacosa]

The duration of ALL AR & MAR with (pseudo)halogen ring-substitutions is very long indeed. p-hydroxylation is the major way the body metabolises this class. Someone has studied all manner of 4-alkyl aminorex derivatives and some o-halogenated analogues.

I've noticed this. Even Wikipedia has a good entry on the topic: https://en.wikipedia.org/wiki/List_of_aminorex_analogues

The paper also provides the EC50 for NET ,DAT & SERT inhibition and release. You will note p-F>p-Cl>p-F. Sadly, most RC chemists simply look for the most potent because it translates into the most profitable. p-Me 4MAR was sold as 'Serotonia' but while it had plenty of SERT activity, it doesn't have enough DAT (or NET, if you like NET inhibition/release). I didn't try it myself, but I have tried p-Me Aminorex and my wife has tried both and was firm on the matter that p-Me AR was the better. What you actually want is a mixture of the p-Me with another analogue that has DAT activity and importantly, a duration as close to the p-Me as possible.

I'd be willing to check out these compounds of course, but what I actually want is: trans-4-methylaminorex. One just needs cathine and KOCN, essentially… plus HCl and some basic glassware.

Oh, and the reason that the 4MARs seem to turn up a lot more often is that they are synthetically simpler.

To be clear, you are referring to 4-methylaminorex here when you say "4MAR" and not to 4'-methyl-aminorex (p-me-AR), right?

Of course, they seill use BrCN for the cyclization.

This is why I prefer the urea intermediate route to the trans enantiomer which eschews the use of BrCN in favor of KOCN.

I mean, people like Uncle Fester have stretched 6 routes into an entire book.

Yeah well, that's probably smarter than selling meth for him… And anyway, what Steve may lack in technical prowess and syntactical precision he makes up for in sheer entertainment value if nothing else, plus I usually learn a few things from perusing his books. The guy knows a lot about electroplating, which, given his real profession, makes a lot of sense.

I am reminded of Eleusis (Jeffrey Jenkins) and also a busted Bee in central Florida named Bill Hahne…

 

[Feretile]

4MAR is an MAOI. Or rather, David Nichols informed me that it was an MAOI. I, for one, am prepared to take his word on it. I think the smart way to make 4MAR is via L-PAC. Now that WILL work with NaHNCN. I've posted a link to the patent.

 

[izo]

Btw @Feretile i noticed your avatar from some story I read some years ago. Was it something about negroes or what?

 

[Feretile]

Btw @Feretile i noticed your avatar from some story I read some years ago. Was it something about negroes or what?

As far as I am aware their is no direct connection to people of African descent. That said, the gentleman did take direct action against a movement that denigrated, stigmatised and murdered people of the basis of certain perceived racial characteristics. He paid the ultimate price for doing so. I chose the image around 35 years ago. It is, I hope, a subtle way of indicating my own humanitarian if not political beliefs.

 

[unodelacosa]

As far as I am aware their is no direct connection to people of African descent. That said, the gentleman did take direct action against a movement that denigrated, stigmatised and murdered people of the basis of certain perceived racial characteristics. He paid the ultimate price for doing so. I chose the image around 35 years ago. It is, I hope, a subtle way of indicating my own humanitarian if not political beliefs.

For anyone scratching their head here… @Feretile's (is this a Shakespeare reference?) profile pic – a mugshot of Dutch communist Marinus van der Lubbe (1909-1934) taken by German police in 1934 (read: Nazis) after arresting young Marinus for setting fire to the German Reichstag building on 27 Feb 1934. This would be the equivalent of setting torch to the House of Parliament / Westminster in the U.K., or the Capitol building where Congress meets in the U.S., or the State Duma in Russia (or the House of Soviets before this), etc. The Nazi's decapitated him for this via guillotine after a quick trial. He was posthumously pardoned in 2011.

 

[izo]

Was this That incident which was staged by the nazis or am I mixing this up?

 

[unodelacosa]

Was this That incident which was staged by the nazis or am I mixing this up?

Well I don't think there's enough evidence to be able to say for sure. This wasn't van der Lubbe's first rodeo, and IIRC historians mostly agree that van der Lubbe did set fire to the Reichstag building. Following the fire, the Nazi's invoked emergency powers granted to them through the Weimar Constitution in order to rearrange the Weimar Republic into the Third Reich. So the conspiracy theory that the Nazi's staged the fire on purpose in order to take over is predicated solely on the convenience factor and not on sufficient evidence to back up the claim.

 

[obviously_not_carl]

I think it's only going to have NET affinity. Plain 3,4-MD AR might be a better target. As I pointed out, that methyl side-chain increases the biosteric minimum. MAR & 4MAR have totally different QSARs and as I mentioned, while AR has 2 isomers, 4MAR has 4 isomers and apart from their being a widely known synthesis for 4MAR, it has no advantages. Actually, their is a second, evcen simpler route to 4MAR.

US3052688A - PROCESS FOR THE PRODUCTION OF 2-AMINO-OXAZOLES

The above is of great utility. After all, it allows the uncontrolled precursor L-PAC to be directly concerted to 4MAR.

I'm not interested in such compounds. A few ring-substituted ARs are of interest but 4MAR is a pleasant stimulant but I've seen the harm caused by such compounds and the (M)AR class also cause heart-valve damage so it's not something I would get involved with.

Still, if L-PAC is suddenly made a controlled precursor, we will know that the DEA reads these pages.... so hello!

You're full of shit and I hope anyone reading your rambling posts will also read this.
Lets not get into the oxazole =/= oxazoline issue for once.

I will just not invest myself in such crap.
Please, reader, be aware that this guy is a liar.

 

[unodelacosa]

You're full of shit and I hope anyone reading your rambling posts will also read this.
Lets not get into the oxazole =/= oxazoline issue for once.
Please, reader, be aware that this guy is a liar.

Seems a bit harsh. Isn’t it more likely that he’s simply mistaken on the subject? Whether by accidental oversight, carelessness, ignorance, or whatever else doesn’t really matter as much as: but what motive would someone have for deliberately lying on something like this?

Either way, I think I see what you mean here. There is a difference in carbon saturation, and what we want is an oxazoline which has one saturated carbon with a double bond, instead of an oxazole which features two double bonds. Probably not easy to interconvert. And I take it this route from L-PAC produces the oxazole, or at least that‘s what you’re saying, right? Thanks for looking out for people’s safety