# US 10,766,895 B2 · Preparation methods for palbociclib free base crystal form A and crystal form B > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,766,895 B2 - Document ID: US10766895B2 - Status: Granted - Kind: B2 - Application number: 16/405,722 - Filed: 2019-05-07 - Published: 2019-08-29 - Granted: 2020-09-08 - Earliest claimed: 2015-11-02 - Assignees: Zhejiang Huahai Pharmaceutical Co., Ltd.; Shanghai Syncores Technologies Inc. Ltd. - Applicants: Zhejiang Huahai Pharmaceutical Co., Ltd.; Shanghai Syncores Technologies Inc. Ltd. - Inventors: Haisheng Fan; Xiaowen Guo; Luning Huang; Hong Gu - Web page: https://patentgrep.com/patent/US10766895B2 ## CPC - C07D 471/04: Ortho-condensed systems - A61P 35/00: Antineoplastic agents - B01D 9/0054: {Use of anti-solvent} - B01D 9/0063: {Control or regulation (control per se G05)} - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## 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 ### Claim 1 A method for preparing crystal form B of palbociclib of the Formula I: the method comprising: 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 an aqueous solvent selected from the group consisting of water and 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 0° C. to 20° C., to obtain crystal form B of palbociclib; wherein crystal form B of palbociclib exhibits an X-ray powder diffraction pattern comprising characteristic peaks having 2θ angles selected from the group consisting of 6.094°, 6.692°, 11.049°, 12.154°, 12.940°, 16.498°, 19.879°, 22.684°, and 26.778°. ### Claim 2 (depends on 1) The method according to claim 1, wherein the pharmaceutically acceptable salt of palbociclib is selected from the group consisting of palbociclib isethionate, palbocklib hydrochloride, palbociclib sulfate, and palbociclib methane sulfonate or a combination thereof. ### Claim 3 (depends on 1) The method according to claim 1, wherein the inorganic base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate. ### Claim 4 (depends on 1) The method according to claim 1, wherein the water-miscible organic solvent is selected from the group consisting of methanol, ethanol and isopropanol. ### Claim 5 (depends on 1) 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. ### Claim 6 (depends on 1) 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. ### Claim 7 (depends on 1) The method according to claim 1, wherein the treatment is performed at a pH greater than 8.0. ### Claim 8 (depends on 1) The method according to claim 1, wherein the treatment is performed at a pH greater than 10.0. ### Claim 9 (depends on 1) The method according to claim 1, wherein the treatment is performed at a temperature in the range of 5 ° C. to 15 ° C.