A possible new approach to 4-MAR

java · Consumer

I've asked this over at WD and had no response hence I will enclose the link with my inquiry .....namely, will the compound made similar to 4-MAR with the cyclization of the amine with the OH except the OH will be on the C3 as opposed to C1 , such as in the case of phenylalaninol. ......will it be active as 4-MAR .......java

This is the 4-MAR link at WD

IndoleAmine · Dreamreader Deluxe

Probably not really, since the distance between the respective active groups isn't the same (ok it almost is besides from that oxygen - is it important?)

And also you have nothing where 4-MAR has a methyl, so your proposal is a structural aminorex analogue (which would make it potentially dangerous due to possible cardiac strokes or something similar, maybe)

(but then again I don't know the exact structure-activity relationship for 4-MAR good enough...)

Guessing about the acitvity of unknown compounds is something that challenges even the most reputable scientists in the field of SAR - only possibility of finding out is considered making clinical trials - maybe more probably bioassay in your case... (be careful if)

java · Consumer

Thanks, just a thought that tangent off while trying to solve the use of the phenylalaninol at a crossroad......amph, poss 4-MAR, methylate the amine and finish off the reduction of OH and then hydrogenate to reduce to the ----, the reason for methylating prior to removal of the OH is to avoid cyclization of the amine and the halogen mid step in the reduction of OH........java

IndoleAmine · Dreamreader Deluxe

Sorry but I don't understand what you meant with "cyclization of the amine and the halogen mid step in the reduction of OH"..(?)

If you meant making & isolating 1-halo-phenylalanine then methylating to n-methyl, then removal of halogen via cat.hydr. (was this what you meant?): Why not simply protect the amine, halogenate the OH then cat.hydrogenate & deprotect again, then methylate the phenylaminopropane to . Neutral

:. ?

If anyone knows if the depicted 4-MAR isomer is active too, then you'd need some kind of cyclization though to arrive at the proposed compnd, obviously..

(confused)

java · Consumer

The problem with chlorinating , in this case , a primary non benzylic amino alcohol(Phenylalaninol), as told by WizardX is the cyclization that occurs in the halogenation of the amine and the chlorine , hence in order to avoid this, and not just waste time in protecting the NH3 with something that I can' use further , using the methylating method with formic acid as documented at the rhodium archives, and then reduce the OH via halogenation and reductive dehalogenation for which it will also reduce the methylated NH and also dehalogenate in one step with catalytic hydrogenation with Pd 10%......java

IndoleAmine · Dreamreader Deluxe

Ah I see - so first methylating phenylalaninol with HCHO* to yield a C=NH-CH3 schiff base (kind of "protection" against said cyclization, so to speak), then halogenation of the OH, followed by cat.hydrogenation to effect both dehalogenation and reduction to the amine at once....

*methylating with HCHO/HCOOH would mean having HCOOH act as a reducing agent already (->leuckart), so I guess you mean forming the imine/schiff base between amine and formaldehyde, resulting in a n-methylimino schiff base - which upon reduction would result in n-methylamino-[whatever]....

Did I get it right now? Smile

java · Consumer

Yes, correct, that hence was one of the cross roads afore mentioned in the tangent thought of making a look alike 4-MAR possibilities, but since I've found nothing over at lycaeum, I decided to search and ask around to see if there has been any research on the subject.....hence brings us back to the oroginal theme of the post........java

IndoleAmine · Dreamreader Deluxe

Hm - sounds like a good plan though if one was going to synth --- from phenylalanine, besides that "pseudo-4-M"-AR..... Wink