Preparation methods for palbociclib free base crystal form A and crystal form B

• US 10,329,290 B2
• Filed: 11/02/2016
• Issued: 06/25/2019
• Est. Priority Date: 11/02/2015
• Status: Active Grant

• Current Assignee: Shanghai SynCores Technologies, Inc. (Zhejiang Huahai Pharmaceutical Company Limited), Zhejiang Huahai Pharmaceutical Company Limited
• Original Assignee: Zhejiang Huahai Pharmaceutical Company Limited
• Inventors: Fan, Haisheng, Guo, Xiaowen, Huang, Luning, Gu, Hong
• Primary Examiner(s): Willis, Douglas M
• Application Number:
  US15/772,497
• Publication Number:
  US 20180319790A1
• Time in Patent Office: 965 Days
• Field of Search: 544279
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B01D 9/0054 Use of anti-solvent
• CPC Class Codes: B01D 9/0063 Control or regulation control per se G05
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Disclosed is a preparation method for a Palbociclib free base crystal form A as shown in Formula I, comprising the following steps: treating a Palbociclib free base and/or a Palbociclib salt compound by using an inorganic base in a water solvent at the temperature of 35 to 100° C. to obtain a Palbociclib free base crystal form A, the water solvent being water or mixed solvent obtained by water and an organic solvent capable of being mixed and disclosed in the water. Also disclosed is a preparation method for a Palbociclib free base crystal form B, comprising the following steps: treating a Palbociclib salt compound by using an inorganic base in a water solvent at the temperature of 0 to 20° C. to obtain a Palbociclib free crystal form B, the water solvent being water or a mixed solvent obtained by water and an organic solvent capable of being mixed and dissolved in the water. The method is safe and convenient in operation and low in pollution, and facilitates industrial production.

Claims

1. A method for preparing crystal form A of palbociclib of the Formula I:

2. The method according to claim 1, wherein the method comprises:

treating a pharmaceutically acceptable salt of palbociclib with a base selected from the group consisting of ammonia, sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate in water or a co-solvent mixture consisting of water and a water-miscible organic solvent selected from the group consisting of methanol, ethanol, isopropanol and tetrahydrofuran, at a temperature in the range of 35°

C. to 100°

C. and a pH greater than 8.0.

3. The method according to claim 1, wherein the pharmaceutically acceptable salt of palbociclib is selected from the group consisting of palbociclib isethionate, palbociclib hydrochloride, palbociclib sulfate and palbociclib methanesulfonate, or a combination thereof.

4. The method according to claim 1, wherein the inorganic base is selected from the group consisting of aqueous ammonia, sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate.

5. The method according to claim 1, wherein the water-miscible organic solvent is selected from the group consisting of methanol, ethanol and isopropanol.

6. The method according to claim 1, wherein the volume ratio of water and the water-miscible organic solvent in the aqueous solvent is 1:

0 to 1;

20.

7. The method according to claim 1, wherein the volume ratio of water and the water-miscible organic solvent in the aqueous solvent is 1:

0 to 1;

2.

8. The method according to claim 1, wherein the treatment is performed at a temperature in the range of 50°

C. to 70°

C.