New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

The 8 -- proposed synthesis Haverford College #402

Closed
rbroadrup-HC opened this Issue Jun 7, 2016 · 7 comments

Comments

Projects
None yet
4 participants
@rbroadrup-HC

rbroadrup-HC commented Jun 7, 2016

Proposed synthetic routes have been developed in collaboration with students as part of an organic chemistry class I teach at Haverford College. The molecules are seen as being desirable targets as per #390. This Issue has been created for community feedback on the routes, which can then be attempted in the lab by us or others.

the 8 rev 2

CC1=NC=C(OCC(O)C2=CC=CC=C2)N3C1=NN=C3C4=CC=C(OC(F)F)C=C4
InChI=1S/C21H18F2N4O3/c1-13-19-25-26-20(15-7-9-16(10-8-15)30-21(22)23)27(19)18(11-24-13)29-12-17(28)14-5-3-2-4-6-14/h2-11,17,21,28H,12H2,1H3
ASWYMQOLUDKKDJ-UHFFFAOYSA-N

@drc007

This comment has been minimized.

Show comment
Hide comment
@drc007

drc007 Jun 7, 2016

I presume there is a deprotonation first before alkylation in the first step?

drc007 commented Jun 7, 2016

I presume there is a deprotonation first before alkylation in the first step?

@rbroadrup-HC

This comment has been minimized.

Show comment
Hide comment
@rbroadrup-HC

rbroadrup-HC Jun 16, 2016

Scheme corrected to include base in first step and to update reference.

rbroadrup-HC commented Jun 16, 2016

Scheme corrected to include base in first step and to update reference.

@MFernflower

This comment has been minimized.

Show comment
Hide comment
@MFernflower

MFernflower Aug 8, 2016

Contributor

@rbroadrup-HC Looks like anything but halogens or hydrogen in the 8 position causes issues - Might want to shelve this one?

800px-pyrazine_substitution_mods

Contributor

MFernflower commented Aug 8, 2016

@rbroadrup-HC Looks like anything but halogens or hydrogen in the 8 position causes issues - Might want to shelve this one?

800px-pyrazine_substitution_mods

@mattodd

This comment has been minimized.

Show comment
Hide comment
@mattodd

mattodd Aug 8, 2016

Member

No, this was factored in - we need ways to access this compound. It'd be useful to measure metabolic stability, particularly in the Aldehyde Oxidase assay, where blocking groups next to aromatic N might be useful. And if we can put a methyl there we might be able to adapt the chemistry to put other things there too. One possibility is that if the potency is reasonable then perhaps we could use the chemistry to put a biotin there for pull-down.

Member

mattodd commented Aug 8, 2016

No, this was factored in - we need ways to access this compound. It'd be useful to measure metabolic stability, particularly in the Aldehyde Oxidase assay, where blocking groups next to aromatic N might be useful. And if we can put a methyl there we might be able to adapt the chemistry to put other things there too. One possibility is that if the potency is reasonable then perhaps we could use the chemistry to put a biotin there for pull-down.

@MFernflower

This comment has been minimized.

Show comment
Hide comment
@MFernflower

MFernflower Aug 8, 2016

Contributor

That is very very interesting. Is there any computational way to access AO stability? As for ideas that have not be tried for the 8 position - HCF2O or CF3 perhaps? maybe even bromine?

@rbroadrup-HC
@mattodd

Contributor

MFernflower commented Aug 8, 2016

That is very very interesting. Is there any computational way to access AO stability? As for ideas that have not be tried for the 8 position - HCF2O or CF3 perhaps? maybe even bromine?

@rbroadrup-HC
@mattodd

@drc007

This comment has been minimized.

Show comment
Hide comment
@drc007

drc007 Aug 8, 2016

I'm not aware of computational studies but I've written a summary here http://www.cambridgemedchemconsulting.com/resources/ADME/aldehyde_oxidase.html

Typically electron-deficient N-heterocycles are a potential flag.

drc007 commented Aug 8, 2016

I'm not aware of computational studies but I've written a summary here http://www.cambridgemedchemconsulting.com/resources/ADME/aldehyde_oxidase.html

Typically electron-deficient N-heterocycles are a potential flag.

@mattodd

This comment has been minimized.

Show comment
Hide comment
@mattodd

mattodd Sep 14, 2016

Member

Closing since taken on to #429

Member

mattodd commented Sep 14, 2016

Closing since taken on to #429

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment