Process for the preparation of chiral 8-(3-aminopiperidin-1-yl)-xanthines

• US 9,499,546 B2
• Filed: 10/06/2014
• Issued: 11/22/2016
• Est. Priority Date: 11/05/2004
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Pfrengle, Waldemar, Pachur, Thorsten, Nicola, Thomas, Duran, Adil
• Primary Examiner(s): SAEED, KAMAL A
• Application Number:
  US14/507,190
• Publication Number:
  US 20150025089A1
• Time in Patent Office: 778 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 473/04 two oxygen atoms
• CPC Class Codes: C07D 473/06 with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3

Abstract

The invention relates to an improved process for preparing enantiomerically pure 8-(3-aminopiperidin-1-yl)-xanthines.

Claims

1. A process for preparing a medicament comprising a first compound of formula

2. The process according to claim 1 wherein R¹ is a (4-methylquinazolin-2-yl)methyl.

3. The process according to claim 2, wherein the phthalyl protecting group of the second compound is detached in the presence of ethanolamine.

4. The process according to claim 2, wherein the phthalyl protecting group of the second compound is detached in the presence of (a) ethanolamine and toluene or (b) ethanolamine and a mixture of tetrahydrofuran and water.

5. The process according to claim 2, further comprising crystallizing the first compound from ethanol or methanol.

6. The process according to claim 2, further comprising crystallizing the first compound from ethanol.

7. The process according to claim 2, wherein the step of detaching the phthalyl protecting group of the second compound is carried out the presence of (a) ethanolamine and toluene or (b) ethanolamine and a mixture of tetrahydrofuran and water, to provide the first compound, and the process further comprises

crystallizing the first compound from ethanol or methanol.

8. The process according to claim 7, wherein the first compound is crystallized from ethanol.