Methods of producing molindone and its salts

Patent metadata

Field	Value
Publication number	US-10676432-B2
Application number	US-201816107836-A
Country	US
Kind code	B2
Filing date	Aug 21, 2018
Priority date	Sep 14, 2012
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

The present invention is directed towards novel methods of synthesis of molindone, synthesis of the intermediates of molindone, and high-purity compositions of molindone. In particular, the invention relates to the methods of synthesis of molindone through the Mannich reaction.

First claim

The invention claimed is:

1. A composition consisting of molindone or its pharmaceutically acceptable salts as the sole active ingredient and comprising formaldehyde, (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine, (E)-N-ethylidenehydroxylamine, and (2Z)-2-(hydroxyimino)propan-1-ol.

2. The composition of claim 1 , comprising less than 1.5 micrograms per human daily dose of each of formaldehyde, (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine, (E)-N-ethylidenehydroxylamine, (2Z)-2-(hydroxyimino)propan-1-ol.

3. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient, formaldehyde, (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine, (E)-N-ethylidenehydroxylamine, and (2Z)-2-(hydroxyimino)propan-1-ol.

4. The compositions of claim 3 , comprising less than 1.5 micrograms per human daily dose of each of formaldehyde, (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine, (E)-N-ethylidenehydroxylamine, (2Z)-2-(hydroxyimino)propan-1-ol.

5. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient and formaldehyde.

6. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient, formaldehyde, and (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine.

7. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient, formaldehyde, (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine, and (E)-N-ethylidenehydroxylamine.

8. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient and (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine.

9. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient, (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine, and (E)-N-ethylidenehydroxylamine.

10. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient, (Z)—N-[(2Z)-2-(hydroxyimino)pentan-3-ylidene]hydroxylamine, (E)-N-ethylidenehydroxylamine, and (2Z)-2-(hydroxyimino)propan-1-ol.

11. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient and (E)-N-ethylidenehydroxylamine.

12. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient, (E)-N-ethylidenehydroxylamine, and (2Z)-2-(hydroxyimino)propan-1-ol.

13. A composition comprising molindone or its pharmaceutically acceptable salts as the sole active ingredient and (2Z)-2-(hydroxyimino)propan-1-ol.

Assignees

• Supernus Pharmaceuticals Inc

Inventors

• Hanbauer Martin
• Nazir Zarghun
• Hildebrand Peter
• Figini Attilia
• Liang Likan
• Fumagalli Tiziano

Classifications

• C07D295/13

  to an acyclic saturated chain · CPC title

• C07D209/08 Primary

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• C07C249/08 Primary

  by reaction of hydroxylamines with carbonyl compounds · CPC title