Intermediates in the enantioselective synthesis of 3-(aminomethyl)-5-methyl-hexanoic acid
AssigneeThe Provost, Fellows and Scholars of the College of the Holy and Undivided Trinity of Queen Elizabeth Near Dublin
InventorsStephen Joseph Connon, Aldo Peschiulli, Lyn Markey
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Abstract
(S)-(+)-3-(aminomethyl)-5-methyl-hexanoic acid or (S)-pregabalin is an anticonvulsive drug. In addition to its use as an anticonvulsive agent, pregabalin has also been indicated as a medicament in the treatment of anxiety, neuropathic pain and pain in patients with fibromyalgia. Provided herein are thioester intermediates in the synthesis of and processes for the synthesis of 3-(aminomethyl)-5-methyl-hexanoic acid in the (R) or (S) configuration.
Claims16
A compound of the general formula (I), or a salt, or ester thereof,
- wherein R1 is selected form the group consisting of C1-C15 alkyl, C3-C15 cycloalkyl, C5-C15 aromatic and combinations thereof.
A process for the preparation of a compound of the formula (I),
- wherein R1 is selected form the group consisting of C1-C15 alkyl, C3-C15 cycloalkyl, C5-C15 aromatic and combinations thereof.
A process for the enantioselective preparation of a compound of the general formula (IV) or (V), or a salt thereof, comprising:
- enantioselective alcoholysis of 3-isobutylglutaric anhydride to afford a compound having an ester functional group,
- wherein enantioselective alcoholysis of 3-isobutylglutaric anhydride comprises ring opening 3-isobutylglutaric anhydride using an achiral alcohol and a chiral catalyst selected from the group consisting of:
- wherein X is O or S;
- Z is a C1 to C5 carbon chain optionally having at least one C—C unsaturated bond;
- M is H, OH, or OMe;
- R1 and R2 may be the same or different and are C1-C15 alkyl, or R1 and R2 taken together with the N to which they are attached define a C3-C15 heterocycloalkyl ring;
- and
- R3 and R4 may be are the same or different and are C1-C15 alkyl, or R3 and R4 taken together define a C3-C15 cycloalkyl ring or C5-C15 aromatic ring.
Dependencies are inferred from the claim text.