Compositions comprising dopamine reuptake inhibitors and methods of making and using the same

A compound of the formula:

• 17
• and pharmaceutically acceptable salts, solvates and clathrates thereof, wherein R is alkyl.

A compound of the formula:

• 18
• and pharmaceutically acceptable salts, solvates and clathrates thereof.

A method of preparing a compound of Formula 2:

• 19
• which comprises contacting cyclobutanecarbonitrile with diisobutylaluminum hydride to form an intermediate;
• and reacting the intermediate with CH3NH2 at a temperature and for a time sufficient to form the compound of Formula 2.

A method of preparing racemic or optically pure desmethylsibutramine which comprises contacting a compound of Formula 2 with a compound of the formula AMX, wherein A is aryl, alkyl, or aralkyl, M is Li or Mg, and X is a halogen atom.

A method of preparing optically pure (R)-desmethylsibutramine or a pharmaceutically acceptable salt, solvate or clathrate thereof which comprises contacting racemic desmethylsibutramine with (R)-mandelic acid in a solvent which is or which comprises a mixture of ethyl acetate and heptane to form the (R)-mandelate salt of (R)-desmethylsibutramine.

A method of preparing optically pure (S)-desmethylsibutramine or a pharmaceutically acceptable salt, solvate or clathrate thereof which comprises contacting racemic desmethylsibutramine with (S)-mandelic acid in a solvent which is or which comprises a mixture of ethyl acetate and heptane to form the (S)-mandelate salt of (S)-desmethylsibutramine.

A method of preparing optically pure (R)-didesmethylsibutramine or a pharmaceutically acceptable salt, solvate or clathrate thereof which comprises contacting racemic didesmethylsibutramine with (R)-mandelic acid in a solvent which is or which comprises a mixture of acetonitrile and methanol to form the (R)-mandelate salt of (R)-didesmethylsibutramine.

A method of preparing optically pure (S)-didesmethylsibutramine or a pharmaceutically acceptable salt, solvate or clathrate thereof which comprises contacting racemic didesmethylsibutramine with (S)-mandelic acid in a solvent which is or which comprises a mixture of acetonitrile and methanol to form the (S)-mandelate salt of (S)-didesmethylsibutramine.

A method of treating or preventing neuropathic pain which comprises administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of a racemic or optically pure sibutramine metabolite, or a pharmaceutically acceptable salt, solvate, or clathrate thereof.