[Fluorine]

Hello Chemical Forums, I'm glad to have joined.

First I wish to note I am not a OChem student and all my knowledge of it comes from studying myself. Currently I am in the last GenChem before OChem. but please approach me as a OChem student. If I do not understand I will learn until I do. I absolutely love OChem, only second to pharmacology.

My question is if we have 3,4-chloromethyl-indole and it reacted with 2-bromo-ethanamine would it cyclize? The hydrogen and chlorine would leave as HCl and N and C would bond together, this occurring twice. I apologize for not having the conditions, catalysts, solvents, etc. but it's currently beyond my understanding. I attached an image of my question. It's the only portion of the full synthesis I am unsure on.

Thank you for your time.

[ooosh]

You may get the product through ring closure,but you may get many other things you don't want to.

[Fluorine]

Would you mind giving me an example(s) of which would by side products - would these be major or minor relative to my initial target? Any information you give will help me learn from this.

Edit: Okay I see where side products would come in...sorry if I'm complicating things can we change the bromine to R, as in any (within reason) group, I guess non-halogen to avoid reacting with the indole. I apologize for this, bromine was never involved initially I'd just rather not reveal the full structure due to hoping it'll be a medicine one day.

[AWK]

2-bromo-ethanamine is very reactive itself.

[Fluorine]

I can see why in retrospect, it would make a ethylene imine ring? Bromine was a very bad last second choice on my part, can we pretend it's R, non-halo group. If it would help let's say it's ethanamine reacting with the 3,4-dichloromethyl-indole.

I guess the quickest way to learn is through embarrassment of your own mistakes.

[Doc Oc]

Yes, you would probably get cyclization.  However, as stated earlier, there is a lot of potential for undesired side products as well.  Amines are very good nucleophiles and they're known not to behave very well in alkylations using alkyl halides (ie; they quaternize to alkyl ammoniums).

Two things work in your favor though:
1) Chlorides aren't great leaving groups so quaternization of the amine would be more difficult, especially if it cyclizes to the tertiary amine.

2) Once the amine substitutes at one of the carbons it should quickly close onto the other as intramolecular reactions are FAR faster than intermolecular reactions.

[discodermolide]

Hello Chemical Forums, I'm glad to have joined.

First I wish to note I am not a OChem student and all my knowledge of it comes from studying myself. Currently I am in the last GenChem before OChem. but please approach me as a OChem student. If I do not understand I will learn until I do. I absolutely love OChem, only second to pharmacology.

My question is if we have 3,4-chloromethyl-indole and it reacted with 2-bromo-ethanamine would it cyclize? The hydrogen and chlorine would leave as HCl and N and C would bond together, this occurring twice. I apologize for not having the conditions, catalysts, solvents, etc. but it's currently beyond my understanding. I attached an image of my question. It's the only portion of the full synthesis I am unsure on.

Thank you for your time.

Looks like you are trying to aim for Lysergic acid analogues from these structures

[Fluorine]

@Original image
Oops indole is missing double bond at position 2-3. Next time I'll prepare ahead before asking, apologies.

@Disco
Very good eye but not completely correct. This is expected to target 5-HT_2A binding pocket however it would not dock the way LSD or other lyseramides do, nor will this be a lysergamide in the end (or even now as it exists). I don't think the moderators will appreciate me discussing non-chemistry in this board so I'll save anything pharmacology to private messages - my door is always open.

@ J-bone
Thank you, this is answered everything I wanted to know.