Methods for isolating propargylated aminoindans

A process for isolating from a reaction mixture a diastereomeric salt of a mono-propargylated aminoindan having the structure

• wherein R1 is H, hydroxyl, alkoxy or
• wherein Y is O or S;
• R2 and R3 is each, independently, C1-8 alkyl, C6-12 aryl, C6-12 aralkyl, each optionally halo substituted, or hydrogen;
• where the reaction mixture further comprises a solvent, a racemic primary aminoindan having the structure
• wherein R1 is defined as above, and a racemic tertiary aminoindan having the structure
• said process comprising
• a) adding a first acid to the reaction mixture in an amount sufficient to form a crystalline acid addition salt of the primary aminoindan;
• b) removing the crystalline acid addition salt said of the primary aminoindan from the reaction mixture, thereby separating the primary aminoindan from the reaction mixture;
• c) adding a second acid to the reaction mixture under conditions suitable for the formation of the crystalline salt of mono-propargylated aminoindan;
• and
• d) recovering the crystalline salt of the mono-propargylated aminoindan.

A process for isolating from a reaction mixture a diastereomeric salt of a mono-propargylated aminoindan having the structure

• wherein R1 is H, hydroxyl, alkoxy or
• wherein Y is O or S;
• R2 and R3 is each, independently, C1-18 alkyl, C6-12 aryl, C6-12 aralkyl, each optionally halo substituted, or hydrogen;
• where the reaction mixture further comprises a solvent, a racemic primary aminoindan having the structure
• wherein R1 is defined as above, and a racemic tertiary aminoindan having the structure
• said process comprising
• a) adding a chiral acid to the reaction mixture in an amount equivalent to the mono-propargylated aminoindan derivative to form a crude diastereomeric salt of the mono-propargylated aminoindan;
• b) separating the crude diastereomeric salt of the mono-propargylated aminoindan from the reaction mixture;
• c) recrystallizing the crude diastereomeric salt of the mono-propargylated aminoindan in water to isolate crystalline diastereomeric salt of the mono-propargylated aminoindan;
• and
• d) recovering crystalline diastereomeric salt of the mono-propargylated aminoindan.

A process for isolating from a reaction mixture a salt of enantiomerically pure N-propargyl-1-aminoindan or a salt of enantiomerically pure 6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan, wherein the reaction mixture further comprises a primary aminoindan having the structure

• wherein R1 is H or
• and a tertiary aminoindan having the structure
• the process comprising crystallizing the salt of enantiomerically pure N-propargyl-1-aminoindan or the salt of enantiomerically pure 6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1 -aminoindan,
• wherein the process is performed without addition of an organic solvent.