Method for preparing donepezil pamoate

Abstract

Disclosed is a new method for preparing a donepezil pamoate (1-benzyl-4-[(5,6-dimethoxyindan-2-one)methyl]piperidine pamoate). The donepezil pamoate prepared by using the method has a high purity and a good flowability.

Claims

1. A method for preparing a crystal form A of a compound of formula I, comprising dissolving the compound of formula I in a reaction solvent and adding another solvent dropwise for precipitation to give the crystal form A of the compound of formula I, wherein the reaction solvent is acetone, and wherein another solvent is water. ##STR00002##

2. The method according to claim 1, wherein dissolving is carried out at a temperature of from 0 to 50° C.

3. The method according to claim 1, wherein dissolving is carried out at a temperature of from 15 to 30° C.

4. The method according to claim 1, wherein adding another solvent dropwise is carried out at a temperature of 0 to 50° C.

5. The method according to claim 1, wherein adding another solvent dropwise is carried out at a temperature of 15 to 30° C.

Description

DESCRIPTION OF THE DRAWINGS

(1) In order to illustrate the examples of the present invention and the prior art more clearly, following are brief descriptions for the drawings used in the examples and the prior art. It is obvious to those skilled in the art that the drawings in the following description are only some examples of the invention, and other drawings may be obtained from these drawings without any inventive effort.

(2) FIG. 1 is an XRPD pattern of donepezil pamoate.

(3) FIG. 2 is a DSC-TGA pattern of donepezil pamoate.

DETAILED DESCRIPTION OF THE INVENTION

(4) The examples of the present invention will be described in detail below with reference to the examples. The examples of the present invention include, but are not limited to, the following examples, which are not intended to limit the scope of the invention.

(5) The X-ray powder diffraction data of the present invention was measured by BRUKER D8 Advance of Bruker Germany Corporation, voltage and current: 40 kV, 40 mA; goniometer: vertical goniometer, radius 280 mm; slit: DS=2°, SS=½°, mask=15 mm, RS=5.0 mm; detector: LYNXEYE detector; scanning mode: continuous scanning; scanning range: 3-40°; counting time per step: 0.2 s; total scanning time: 390 s.

(6) The differential scanning calorimetry pattern of the present invention was measured by TGA/DSC 2 from METTLERSwitzerland Corporation, with a temperature range of 30-300° C. and a temperature increase rate of 10° C./min.

Example 1: Preparation of Donepezil Pamoate

(7) 5 ml of acetone was added to 200 mg of donepezil pamoate sample to completely dissolve it at room temperature. 15 ml of water was added dropwise at room temperature. Solids appeared immediately during the addition and dispersed well. After the addition was completed, stirring was continued for 2 hours and then the reaction mixture was filtered. The filter cake was washed with 50 ml of water, filtered under vacuum for 10 min and dried in vacuo to obtain 180 mg of donepezil pamoate sample. The crystal form of the obtained sample was Form A.

Example 2: Preparation of Donepezil Pamoate

(8) 50 ml of acetone was added to 2 g of the donepezil pamoate sample to completely dissolve it at room temperature. 150 ml of water was added dropwise at room temperature. Solids appeared immediately during the addition and dispersed well. After the addition was completed, stirring was continued for 2 hours and then the reaction mixture was filtered. The filter cake was washed with 50 ml of water, filtered under vacuum for 10 min and dried in vacuo to obtain 1.8 g of donepezil pamoate sample. The crystal form of the obtained sample was Form A.

Example 3: Preparation of Donepezil Pamoate

(9) 500 ml of acetone was added to 20 g of the donepezil pamoate sample to completely dissolve it at room temperature. 1.5 L of water was added dropwise at room temperature. Solids appeared immediately during the addition and dispersed well. After the addition was completed, stirring was continued for 2 hours and then the reaction mixture was filtered. The filter cake was washed with 500 ml of water, filtered under vacuum for 10 min and dried in vacuo to obtain 18 g of donepezil pamoate sample. The crystal form of the obtained sample was Form A.

(10) The above are only preferred examples of the present invention, and are not intended to limit the present invention. Any modifications, equivalents, improvements, etc., which are made within the spirit and principles of the present invention, should be included within the scope of the present invention.