Polymorphs

• US 10,301,313 B2
• Filed: 10/05/2017
• Issued: 05/28/2019
• Est. Priority Date: 05/04/2006
• 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: Sieger, Peter, Kemmer, Dirk, Kohlbauer, Peter, Nicola, Thomas, Renz, Martin
• Primary Examiner(s): Jarrell, Noble E
• Assistant Examiner(s): Kenyon, John S
• Application Number:
  US15/725,426
• Publication Number:
  US 20180099969A1
• Time in Patent Office: 600 Days
• 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 2200/13 Crystalline forms, e.g. polymorphs
• 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 polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament.

Claims

1. A method of preparing anhydrous polymorph D of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterized in that it melts at 150±

3°

C., the method comprising heating polymorph C of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine at a temperature of 100°

C. to lose water, wherein polymorph C is characterized in that it loses water at a temperature of 30-100°

C. and exhibits further thermal effects at a temperature of about 150°

C. and about 175°

C. in a differential scanning calorimetry (DSC) analysis.

2. The method according to claim 1 wherein polymorph C is obtained by a method comprising:

(a) refluxing a solution of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in methanol to provide a hot methanolic solution,

(b) cooling the hot methanolic solution to a temperature of 40-60°

C. to provide a cooled methanolic solution,

(c) adding tert-butylmethylether to the cooled methanolic solution to form a suspension,

(d) cooling the suspension first to a temperature of 15-25°

C. and then to a temperature of 0-5°

C. to provide crystals,

(e) suction filtering the crystals, and

(f) drying the crystals obtained in step (e) in vacuo at a temperature of 70°

C. to provide Polymorph C.

3. The method according to claim 2, wherein the X-ray powder diagram of Polymorph C has characteristic reflections at the following d values:

12.90 Å

, 11.10 Å

, 6.44 Å

, 3.93 Å and

3.74 Å

.

4. The method according to claim 2, wherein the hot methanolic solution obtained in step (a) is filtered before cooling in step (b).