Bromo-DragonFLY

IUPAC name; (1-(8-Bromobenzo[1,2-b;4,5-b]difuran-4-yl)-2-aminopropane

Other names; Bromo-benzodifuranyl-isopropylamine, Bromo-DragonFLY



Molecular formula; C13-H12-Br-N-O2

Molecular mass; 294.14g/mol

Melting point; hydrochloride decomposes at 240*C

Drugs Acting on 5-Hydroxytryptamine Receptors

Dihydrobenzofuran Analogues of Hallucinogens. 3.1 Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups2
Aaron P. Monte,‡ Danuta Marona-Lewicka, Matthew A. Parker, David B. Wainscott,† David L. Nelson,† and
David E. Nichols
J. Med. Chem. 1996, 39, 2953-2961
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A novel (benzodifuranyl)aminoalkane with extremely potent activity at the 5-HT2A receptor.
Parker, M.A.; Marona-Lewicka, D.,; Lucaites, V.L.; Nelson, D.L.; Nichols, D.E.;  
J Med Chem 1998, 41, 26, 5148
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Alkylation of hydroquinone (I) with 1-bromo-2-chloroethane and K2CO3 in acetone gave the bis(2-chloroethyl)ether (II), which was then brominated in the presence of Fe in CCl4 to provide dibromocompound (III). Lithiation, followed by intramolecular cyclization, upon treatment with two equivalents of n-BuLi in THF at 0 C furnished the tetrahydrobenzodifuran (IV). Subsequent formylation with dichloromethyl methyl ether in the presence of SnCl4 yielded aldehyde (V). This was condensed with nitroethane in the presence of ammonium acetate, and the resulting nitropropene compound (VI) was reduced with LiAlH4 to afford the aminopropane (VII). Protection of (VII) with trifluoroacetic anhydride and Et3N gave trifluoroacetamide (VIII), and then bromination in AcOH afforded bromide (IX). The aromatic benzodifuran (X) was obtained by dihydrogenation with dichlorodicyanobenzoquinone (DDQ) in toluene, and finally, the amide was deprotected by hydrolysis with NaOH to afford the target amine, which was isolated as the hydrochloride salt.

Phenmetrazine

IUPAC name; 3-methyl-2-phenylmorpholine

Other names; Oxazimedrine, Preludin(US), Anorex(US), Cafilon(Jpn), Marsin(Isr)

(V)

Molecular formula; C11-H15-N-O

Molecular mass; 177.2456 g/mol

Drugs Acting as Norepinephrine and Dopamine releasing agents

Process for the production of substituted Morpholines
US Patent 2,835,669
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Amine alkylation between a-bromopropiophenone(I) and N-benzylmonoethanolamine(II) produces 2-(benzyl(2-hydroxyethyl)amino)-1-phenylpropan-1-one(III). Hydrogenation in the presence of palladium on charcoal affords deprotection and reduction giving 2-(2-hydroxyethylamino)-1-phenylpropan-1-ol (IV), upon standing with conc acid (H2SO4 or HCl) overnight (or warming for 6 hours) ring closure leading to the required morpholine derivative (3-methyl-2-phenylmorpholine (V)) is complete.
(I)    (II)

(III)  (IV)


These are a couple of syntheses that are a bit more difficult to come across, I am currently researching the 3,4-methylenedioxy analog of Phenmetrazine if my research keeps going well I hope to produce it soon.

Dihydrobenzofuran Analogues of Hallucinogens. 3.1 Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups2
Aaron P. Monte,‡ Danuta Marona-Lewicka, Matthew A. Parker, David B. Wainscott,† David L. Nelson,† and
David E. Nichols
J. Med. Chem. 1996, 39, 2953-2961
http://nelix.id.au/papers/unsorted/www.murple.net/nichols/nichols-dihydrobenzofuran-3-fly.pdf

"As there was only one remaining aromatic position, 7a (VII)was easily brominated by treatment with elemental bromine in acetic acid to afford the target compound 7b(bromodragonfly)."

I do not know why they put that protection in, as you pointed out it is not needed.

very nice naf I wonder if there is a way around that butyl lithium though.

closing rings is not realy something I have looked a lot into.

I wonder if methyl lithium would do the trick instead as methyl lithium is a little more otc.

well we can do away with the hydride in that one straight away and ill stick to perchlorate thankyou very much

as for the trimethyl sulphoxonium iodide methyl iodide and DMSO is not such a hard one to come up with.

very nice not so into the amphet flies as there not as nice ive heard as the 2c flies.

excellent very nice indeed.

arrrg so much chem to do but it seems it all is starting to fall into common reagents so im getting there.
patience is the key.

http://www.simafex.com/_pdf/tmsoi.pdf

In regards to the Bromo-DragonFLY, What protecting group, besides the trifluoroacetic anhydride, could be used? I know there are several other protecting groups for NH2, but are their more OTC ones that will work in this synthesis? Perhaps acetic anhydride would work?

Also, this may be a good starter for a do-able HemiFLY synthesis? IIRC hemiFLY is more attractive, but currently I can't find any references on its psychoactive or toxicity effects.

Also Does anyone have any information about the N substituted tetrahydrofuran (AKA... tetrahydropyrrole) ring derivatives of the FLY class of PEAs? I think these would be very interesting, and 'probably' not much harder to make -- using 1,4-diaminobenzene in place of the 1,4-dihydroxylbenzene?

http://upload.wikimedia.org/wikipedia/commons/4/48/2C-B-FLY_SAR.png

I was thinking of something exactly like Bromo-DragonFLY but instead of the oxygen in the secondary rings, have a nitrogen. That information is interesting though, thanks!

It is amazing how many possible molecules their are to just affect one receptor.

Interesting I didn't even consider that... but I was thinking the nitrogen could act as an H donor like it does, to my understanding, in LSD. It seems like the 2C-T and ALEPHs you are talking about have the sulfur in the wrong place for this... not sure.

Look at this article and you'll see what I am talking about. -- Sulfur, however, might be an even better H donor? I'd imagine that wouldn't be to hard to make either...

http://www.bluelight.ru/vb/showthread.php?t=167978

PS. I found this image funny, perhaps it is a real drug? http://img240.imageshack.us/img240/5279/lsd25fullyaromaticiodod.png
It is a hybrid between the dragon fly and LSD, obviously.


It just seems like the nitrogen isn't a new guy when it comes to the 5HT2A activation, and I can imagine perhaps having a lot of 2C-X, DOX, DragonFLY and so on analogues work out pretty well... or perhaps benzofuran Lysergic acid derivatives also acting pretty well.

I'm a noob to pharmacology though - but I'm slowly learning. 

Ah, I didn't see that till I posted, Anyways - the thiomescaline is more active, so maybe a thiofuran type ring on a dragonfly would be really affective.
Like I said, I don't know much about it and I'll have to look more into Nichols' proposed structure of the 5-HT2 receptor.

PS. a mescaline derivative with NHCH3 on it might be interesting! 3,4-dimethoxy-5-methylamino-PEA or something like that? Perhaps that is already out there?

I haven't seen that particular incarnation.  It's hard to tell with mescaline.  A thio group in the 4 position increases potency, but that should be the part of the molecule that needs to be hydrophobic based on the models.  Mescaline seems to just not fit quite right, which probably explains the high dosage needed, and might lend some support to the theory that a metabolite is responsible for its activity rather than the molecule itself.

Yeah, but see the addendum above, I personally couldn't think of anything worse than a 24+ hour "BAD" trip and that is what these are known for, seriously extended duration and bad-trips. With DOC for example, the 1kg of R-DOC would give 2M hits (0.5mg/hit extrapolated from the general 1:10 normally associated with the relative strength of the Racemate:R isomer in this series, 5mg of the racemate being the effective dose in PIhkAL), making it small scale enough to appeal to even the hardest core tripper, but they can still be over and done with within a reasonable period.