Azaspirone pharmaceutical composition and preparation method thereof
A composition and compound technology, applied in the directions of drug combination, drug delivery, pharmaceutical formulation, etc., to achieve the effect of reducing adverse reactions, shortening production cycle, and low content of related substances
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0046] 1. Preparation of cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide
[0047] Prepare cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide according to the method reported in the literature (China New Technology and New Products. 2014,8,13), and its The content of related substances is 2.7%. Among them, the HPLC (High Performance Liquid Chromatography) test conditions are: use octadecylsilane bonded silica gel as filler, 0.01mol / L potassium dihydrogen phosphate solution (adjust pH to 7.5 with 10% sodium hydroxide solution)-acetonitrile (80:20) is the mobile phase, the detection wavelength is 243nm, and the measured purity is 97.3%.
[0048] 2. Purification of cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide
[0049] (i) Weigh 100.0 g of cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide prepared in the above step 1, add a mixed solvent of 400 mL ethanol and 400 mL water, and heat to solvent reflux , after stirring for 1 hour, lower the temperature to 50±5°C and stir for 1 hour, ...
Embodiment 2
[0058] Using cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide prepared under the conditions of 1-5 in Table 1 as raw material, prepare tandospirone citrate according to the above method The composition, as tested by HPLC, shows that the content of tandospirone citrate is above 98.0%, and the contents of related substances are shown in Table 2.
[0059] Table 2. Test results
[0060]
[0061]
[0062] Note: "--" means not detected.
[0063] From the above, it can be known that the purification process of the intermediate cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide in Examples 1 and 2 uses environmentally friendly, safe, low-toxic / non-toxic reagent, and has the advantages of high yield and high purity; in addition, the preparation of the tandospirone composition adopts a two-step one-pot process, without the need to separate the intermediate products generated by the reaction, which greatly improves the industrial production efficiency and shortens the production cycle...
Embodiment 3
[0065] 1. The preparation of cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide is the same as Step 1 of Example 1.
[0066] 2. Purification of cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide
[0067] (i) Weigh 100.0 g of cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide prepared in the above step 1, add a mixed solvent of 400 mL ethanol and 400 mL water, and heat to solvent reflux , stirred for 1 hour, cooled naturally to room temperature, placed at -10±5°C for 2 to 3 hours, filtered with suction, added a mixed solvent of 200 mL of ethanol and 200 mL of water to the filter cake, heated to solvent reflux, stirred for 1 hour, and naturally cooled to room temperature. Place at 5±5°C for 2-3 hours, filter, and dry the filter cake to obtain 99.5 g of cis-exo-bicyclo[2.2.1]heptane-2,3-dicarboximide with a yield of 99.5%. The purity measured by HPLC is greater than 99.5%, and the detection conditions are the same as step 1 of Example 1, wherein, impurity 1 (cis-exo-bicyclo[2.2.1]hept-5-...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More