US 8,008,500 B2 · Intermediates useful for making tetrabenazine compounds

Abstract

A method of preparing a tetrabenazine compound (TBZ compound) having structure I comprising the steps of reacting a nucleophilic alkenyl species with aldehyde compound II and oxidizing the resultant allylic alcohol to provide enone III. The protecting group P1 on the tetrahydroisoquinoline nitrogen is removed and the resultant deprotected intermediate is induced to undergo an amino cyclization reaction to provide a product TBZ compound having structure I. The method may be used to prepare either enantiomeric form of tetrabenazine; (+)-tetrabenazine or (−)-tetrabenazine. Alternatively the method may be adapted to provide a mixture enriched in one tetrabenazine enantiomer, a racemic mixture, or a diastereomeric mixture of tetrabenazine compounds. In addition, the present invention provides novel synthetic intermediate compositions which may be used to prepare either or both enantiomers of tetrabenazine, derivatives of tetrabenazine, and analogs of tetrabenazine.

Claims23

Dependent claims

A tetrahydroisoquinoline compound having structure III

wherein R1-R4 are independently hydrogen or an isotope thereof, a halogen atom, a C1-C20 aliphatic radical, a C2-C20 cycloaliphatic radical, or a C2-C20 aromatic radical, wherein at least one of R1-R4 is not hydrogen;
R5-R11 are independently hydrogen or an isotope thereof, a C1-C20 aliphatic radical, a C2-C20 cycloaliphatic radical, or a C2-C20 aromatic radical;
and P1 is a protecting group.

Dependencies are inferred from the claim text.

Intermediates useful for making tetrabenazine compounds

Life of this patent

Intermediates useful for making tetrabenazine compounds

Life of this patent

Abstract

Claims23