Acetone solvate of dimethoxy docetaxel and its process of preparation

• US 7,241,907 B2
• Filed: 09/17/2004
• Issued: 07/10/2007
• Est. Priority Date: 09/19/2003
• Status: Active Grant

• Current Assignee: Sanofi Mature IP
• Original Assignee: Aventis Pharma SA (Sanofi )
• Inventors: Perrin, Marc-Antoine, Didier, Eric
• Primary Examiner(s): Seaman; Margaret D.
• Assistant Examiner(s): Rahmani; Niloofar
• Application Number:
  US10/944,254
• Publication Number:
  US 20050065138A1
• Time in Patent Office: 1,026 Days
• Field of Search: 549/510
• US Class Current: 549/510
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07D 305/14 condensed with carbocyclic rings or ring systems

Abstract

This invention discloses and claims an acetone solvate of dimethoxydocetaxel or 4-acetoxy-2α-benzoyloxy-5β,20-epoxy-1-hydroxy-7β,10β-dimethoxy-9-oxotax-11-en-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate and its preparation by crystallization from an aqueous/acetone solution.

Claims

1. An acetone solvate of 4-acetoxy-2α

-benzoyloxy-5β

,20-epoxy-1-hydroxy-7β

,10β

-dimethoxy-9-oxotax-11-en-13α

-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate.

2. An acetone solvate of 4-acetoxy-2α

-benzoyloxy-5β

,20-epoxy-1-hydroxy-7β

,10β

-dimethoxy-9-oxotax-11-en-13α

-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate comprising from about 5 to about 7 percent by weight of acetone.

3. A process for the preparation of the acetone solvate of 4-acetoxy-2α

-benzoyloxy-5β

,20-epoxy-1-hydroxy-7β

,10β

-dimethoxy-9-oxotax-11-en-13α

-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate, which comprises;

crystallizing 4-acetoxy-2α

-benzoyloxy-5β

,20-epoxy-1-hydroxy-7β

,10β

-dimethoxy-9-oxotax-11-en-13α

-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate from a mixture of water and acetone, which comprises seeding the solution with a suspension of said product in an acetone/water mixture and then subsequently treating with water, and which comprises drying the product obtained under reduced pressure.

4. The process as set forth in claim 3, wherein the seeding is carried out at a concentration of from about 60 to about 80 g per liter of a mixture comprising an acetone/water ratio by volume of from about 65/35 to about 75/25.

5. The process as set forth in claim 4, wherein the seeding is carried out in a mixture comprising an acetone/water ratio by volume of about 68/32.

6. The process as set forth in claim 3, wherein the acetone/water mixture by volume at the end of precipitation is from about 70/30 to about 30/70.

7. The process as set forth in claim 6, wherein the acetone/water mixture by volume at the end of precipitation is about 45/55.

8. The process as set forth in claim 3, wherein the crystallization process takes place at about 20±

5°

C.

9. The process as set forth in claim 4, wherein the crystallization process takes place at about 20±

5°

C.

10. The process as set forth in claim 5, wherein the crystallization process takes place at about 20±

5°

C.

11. The process as set forth in claim 6, wherein the crystallization process takes place at about 20±

5°

C.

12. The process as set forth in claim 7, wherein the crystallization process takes place at about 20±

5°

C.

13. The process as set forth in claim 3, wherein drying is carried out at a temperature in the range of from about 30 and about 60°

C.

14. The process as set forth in claim 13, wherein drying is further carried out under a pressure in the region of 0.7 kPa.

15. The process as set forth in claim 3, wherein drying is carried out at a temperature of about 40°

C. under a pressure in the region of 0.7 kPa.

16. The process as set forth in claim 3, wherein the preparation is carried out directly starting from the acetone solution of 4-acetoxy-2α

-benzoyloxy-5β

,20-epoxy-1-hydroxy-7β

,10β

-dimethoxy-9-oxotax-11-en-13α

-yl (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate obtained by deprotection in an acid medium of the ester 4-acetoxy-2α

-benzoyloxy-5β

,20-epoxy-1-hydroxy-7β

,10β

-dimethoxy-9-oxotax-11-en-13α

-yl (2R,4S,5R)-3-tert-butoxycarbonyl-2-(4-methoxyphenyl)-4-phenyloxazolidine-5-carboxylate.