Polymorphs

Patent metadata

Field	Value
Publication number	US-10301313-B2
Application number	US-201715725426-A
Country	US
Kind code	B2
Filing date	Oct 5, 2017
Priority date	May 4, 2006
Publication date	May 28, 2019
Grant date	May 28, 2019

Abstract

The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament.

First claim

The invention claimed is:

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).

Assignees

• Boehringer Ingelheim Int

Inventors

• Sieger Peter
• Kemmer Dirk
• Kohlbauer Peter
• Nicola Thomas
• Renz Martin

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P3/08

  for glucose homeostasis (pancreatic hormones A61P5/48) · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title