(S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid, and related compounds as GABA aminotransferase inactivators for the treatment of epilepsy, addiction and hepatocellular carcinoma
US-9993449-B2 · Jun 12, 2018 · US
Process for the synthesis of (s) 3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid
US10836708B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10836708-B2 |
| Application number | US-201916423761-A |
| Country | US |
| Kind code | B2 |
| Filing date | May 28, 2019 |
| Priority date | May 25, 2018 |
| Publication date | Nov 17, 2020 |
| Grant date | Nov 17, 2020 |
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Abstract
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Provided herein are processes, compounds and compositions for making (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid. Also provided herein a pharmaceutical compositions containing (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid.
First claim
Opening claim text (preview).
What is claimed is: 1. A process for preparing (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (1) or salt thereof comprising: converting (1R,4S)-(−)-2-azabicyclo[2.2.1]hept-5-en-3-one (2) to (1R,4S)-(−)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (3); converting (1R,4S)-(−)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (3) to (1R,4R,6S,7R)-(+)-7-bromo-2-(4-methoxybenzyl)-3-oxo-2-azabicyclo[2.2.1]heptan-6-yl acetate (4); converting (1R,4R,6S,7R)-(+)-7-bromo-2-(4-methoxybenzyl)-3-oxo-2-azabicyclo[2.2.1]heptan-6-yl acetate (4) to (1R,4R,6S,7R)-(+)-7-Bromo-6-hydroxy-2-(4-methoxybenzyl)-2-aza-bicyclo[2.2.1]heptan-3-one (25); converting (1R,4R,6S,7R)-(+)-7-Bromo-6-hydroxy-2-(4-methoxybenzyl)-2-aza-bicyclo[2.2.1]heptan-3-one (25) to (1R,4R,7R)-(+)-7-bromo-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptane-3,6-dione (5); converting (1R,4R,7R)-(+)-7-bromo-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptane-3,6-dione (5) to (1R,4R,7R)-(+)-7-bromo-6-(difluoromethylene)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptan-3-one (6); converting (1R,4R,7R)-(+)-7-brom o-6-(difluoromethylene)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptan-3-one (6) to (1R,4R,7R)-(+)-7-bromo-6-(difluoromethylene)-2-azabicyclo[2.2.1]heptan-3-one (7); converting (1R,4R,7R)-(+)-7-bromo-6-(difluoromethylene)-2-azabicyclo[2.2.1]heptan-3-one (7) to (1R,4R,7R)-(+)-7-bromo-6-(difluoromethylene)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptan-3-one (8); converting (1R,4R,7R)-7-bromo-6-(difluoromethylene)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptan-3-one (8) to (S)-3-((tent-butoxycarbonyl)amino)-4-(difluoromethylene)cyclopent-1-ene-1-carboxylic acid (19); and converting (S)-3-((tent-butoxycarbonyl)amino)-4-(difluoromethylene)cyclopent-1-ene-1-carboxylic acid (19) to (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (1), optionally followed by acidification to provide the hydrochloride salt thereof. 2. A process for preparing (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (1) or salt thereof comprising: converting (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (2) to (1R,4R,6S,7R)-7-bromo-2-(4-methoxybenzyl)-3-oxo-2-azabicyclo[2.2.1]heptan-6-yl acetate (4); converting (1R,4R,6S,7R)-7-bromo-2-(4-methoxybenzyl)-3-oxo-2-azabicyclo[2.2.1]heptan-6-yl acetate (4) to (1R,4R,7R)-7-bromo-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptane-3,6-dione (5); converting (1R,4R,7R)-7-bromo-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptane-3,6-dione (5) to (1R,4R,7R)-7-bromo-6-(difluoromethylene)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptan-3-one (6); converting (1R,4R,7R)-7-bromo-6-(difluoromethylene)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptan-3-one (6) to (1R,4R,7R)-7-bromo-6-(difluoromethylene)-2-azabicyclo[2.2.1]heptan-3-one (7); converting (1R,4R,7R)-7-bromo-6-(difluoromethylene)-2-azabicyclo[2.2.1]heptan-3-one (7) to (1R,4R,7R)-7-bromo-6-(difluoromethylene)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptan-3-one (8); converting (1R,4R,7R)-7-bromo-6-(difluoromethylene)-2-(tert-butoxycarbonyl)-2-azabicyclo[2.2.1]heptan-3-one (8) to methyl (S)-3-((tert-butoxycarbonyl)amino)-4-(difluoromethylene)cyclopent-1-ene-1-carboxylate (9); and converting methyl (S)-3-((tert-butoxycarbonyl)amino)-4-(difluoromethylene)cyclopent-1-ene-1-carboxylate (9) to (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (1), optionally followed by acidification to provide the hydrochloride salt thereof. 3. The process according to claim 2 , wherein (1R,4S)-2-azabicyclo[2.2.1]hept-5-en-3-one (2) is converted to (1R,4S)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (3); and (1R,4S)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]hept-5-en-3-one (3) is converted to (1R,4R,6S,7R)-7-bromo-2-(4-methoxybenzyl)-3-oxo-2-azabicyclo[2.2.1]heptan-6-yl acetate (4).
Assignees
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Classifications
Optical isomers · CPC title
Antineoplastic agents · CPC title
for treating abuse or dependence · CPC title
Antiepileptics; Anticonvulsants · CPC title
the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil · CPC title
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- What does patent US10836708B2 cover?
- Provided herein are processes, compounds and compositions for making (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid. Also provided herein a pharmaceutical compositions containing (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid.
- Who is the assignee on this patent?
- Univ Northwestern
- What technology area does this patent fall under?
- Primary CPC classification C07C227/20. Mapped technology areas include Chemistry & Metallurgy.
- When was this patent published?
- Publication date Tue Nov 17 2020 00:00:00 GMT+0000 (Coordinated Universal Time) (B2). Legal status and post-grant events are not shown on this page.
- What related patents are in patentsdb?
- We list 3 related publications on this page (citations in our corpus or others sharing the same primary CPC).