5-EtO-DMT/DIPT?

[yellium]

Well, anyone ever tried that one?

[Rhodium]

According to the literature, no 5-ethoxy tryptamines has been tried in humans. But it is sure an interesting area to investigate.

http://rhodium.lycaeum.org

[yellium]

Especially since they're not scheduled, and the 5-position seems to be the equivalent of the 4-position in phenethylamines:

(quoting

http://www.phc.vcu.edu/rag/serotonin/

 

On the basis of our earlier SAFIR work, and using a calf 5-HT1D receptor preparation, we felt that extension of a 5-position substituent on a tryptamine scaffold should ultimately result in the desired selectivity. That is, both receptor populations can accommodate bulk at the tryptamine 5-position but, the two receptors being different, it seemed logical that these two regions of bulk tolerance should be different. Indeed, we were successful in identifying NOT, or 5-(nonyloxy)tryptamine. We found that as the length of the 5-position substituent increased, 5-HT1D selectivity began to increase. Unfortunately, affinity at both populations began to decrease as the alkyl chain was extended. A nonyloxy substituent was found to be optimal. NOT was found to bind with high affinity and with 100-fold selectivity for 5-HT1D versus 5-HT1A receptors.

 Other 5-position substituents were examined, including arylalkyloxy derivatives, and analogs were prepared that displayed > 400-fold selectivity for 5-HT1D versus 5-HT1A receptors. We also found that the 5- position oxygen atom is not required for 5-HT1D binding and that shorter chains are tolerated in the absence of the oxygen atom.

[foxy2]

How about 5-methylthio tryptamines or 5-ethylthio tryptamines?
Ooops guess Shulgin beat me to the old methyl thio  

Do Your Part To Win The War

[phaidon]

Well boys,

anyone got ideas for the synthesis of 5-ethoxy-whatever to start off? I don't think it's readily available.
(5-EtO-T, 5-EtO-Try or 5-EtO-I-3-CHO that is.)


Laters,

-- phaidon, son of apollon

I scorched the Earth, now what do I do tomorrow?

[Lilienthal]

The method of choice would be p-ethoxy-phenylhydrazine + dimethylaminobutyraldehyde acetal condensation. For this reaction you can find some (important) postings at the Hive.

For the higher alkyloxy DMT analogs there are no 5-HT_2A binding data. I heard that 5-nonyloxy-DMT at a low (undetermined) dosis resulted in a two-day very strong (but not unpleasant) tiredness, possibly an indicator of 5-HT2(C?) antagonism.

I found the following literature in my references database:

Methylthio-DMT receptor data:

J. Med. Chem. 25, 1381 (1982) T. B. Kline et al. (Lil. Ref. # 261)
4-, 5-, 6-(di)MeO- and MeS-DMT, rat stomach fundus strip data, photoelectron spectra

5-Alkoxy-tryptamines:

J. Med. Chem. 37, 2828 (1994) R. A. Glennon et al. (Lil. Ref. #384)
NonO-tryptamine, serotonin, and sumatriptan, 5-HT1A, 1B, 1Dalpha, 1Dbeta, 2A, 2C, and 3 receptor binding data, AC activity data

J. Med. Chem. 39, 314 (1996) R. A. Glennon et al. (Lil. Ref. #385)
AlkylO-tryptamine 37 subst. 5-alkyl-O- and 5-alkanoyl-O-tryptamines and cyclic analogs, human 5-HT1A, 1Dalpha, and 1Dbeta receptor binding data, NonO-DMT from tryptamine with NaCNBH4, formaline, and acetic acid, yield 25%

J. Chem. Soc. -, 1573 (1955) Ph. Buu-Hoï et al. (Lil. Ref. #386)
p-AlkylO-anilines p-alkylO-anilines from p-OH-formanilide via p-alkoxyformanilide with alkyl bromide, and alkaline hydrolysis

J. Med. Chem. 27, 347 (1984) C. D. Selassie et al. (Lil. Ref. #387)
p-AlkylO-anilines p-alkylO-anilines from p-OH-acetanilide via p-alkoxyacetanilide with alkyl bromide, and alkaline hydrolysis

J. Med. Chem. 15, 307 (1972) E. M. Kosower et al. (Lil. Ref. #388)
p-Pentyl-O-phenylhydrazine p-pentyl-O-phenylhydrazine from p-pentyl-O-aniline with 1. NaNO2 / HCl 2. SnCl2 / HCl

Coll. Czech. Chem. Commun. 38, 595 (1972) M. Machková et al. (Lil. Ref. #389)
p-AlkylO-anilines p-alkylO-anilines from p-OH-trifluoroacetanilide via p-alkoxy-trifluoroacetanilide with alkyl bromide, and gentle alkaline hydrolysis

[iasion]

How about 5-bromoindole + KOEt + 18-crown-6, to get 5-ethoxyindole, and then proceed via oxalyl chloride or any other route to the desired tryptamine. With the crown either, would this be a reasonable substitution?

D=MT^2

[terbium]

If I had oxalyl chloride, LAH and the facilities to work with them I would forget about the 5-alkoxy tryptamines and make good old DMT.

[foxy2]

Some people just want to "Go where no man has gone before"

   

Do Your Part To Win The War

[Lilienthal]

Here are some references from Beilstein (even if bromo-indoles are not the cheapest):

6-Br-indole, 6-Meo-N-pivaloyl-tryptamine (MeONa, DMF, CuI, 8 - 12 h, 58% - 73%): J.Heterocycl.Chem. 20, 349 (1983)

Br-(tetrahydro-)carbazoles (MeONa, DMF, CuI, 7 h, heating, 4% - 87%): Chem.Pharm.Bull. 29, 1231 (1981)

3,4-subst.-5-Br-indole (MeONa, DMF, CuI, 5 h, 130°, 80%): J.Med.Chem. 31, 1746 (1988)