In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 22884-10-2 as follows. COA of Formula: C5H6N2O2
PREPARALION OF ZLD-AC CRYSTAL FORM XNII; Example 18 :; A 3L reactor equipped with A mechanical stirrer, a thermometer, a reflux condenser and a dropping funnel, was loaded with 1-IMIDAZOLEACETIC acid (70. OG, 0. 56MOLE), Phosphorous acid (136. 7g, 1.67mole) and Silicon oil (M-350) (490ML). The suspension was heated to 80C and Phosphorous oxychloride (194. 4ML, 2.08mole) was added drop-wise during 4 hours. The reaction mixture was stirred at 80C for 22 hours. Then water (490ML) was added slowly at 80C. The mixture was stirred vigorously for about 30 minutes. Then the silicon oil phase and the aqueous phase were separated. The aqueous phase was put in a clean reactor and heated to 97C for 17.5 hours. Then absolute Ethanol (490ML) was added and the solution was stirred at reflux (87C) for 2 hours. The solution was then cooled to 70C-72C during about 1 hour and was kept at this temperature for 1 hour. After cooling to 25C during 2.5 hours and stirring at this temperature for 1 hour, half of the product was filtered, washed with small amount of cold water and dried in a vacuum oven at 50C for 20 hours to obtain 50.8g of Zoledronic acid crystal form XVIII (MS- 507-CROP I, LOD by TGA=1.9%). The rest of the suspension was cooled to 0C during 2 hours and was stirred at this temperature for about 16 hours. Then the product was filtered and dried in a vacuum oven at 50C for 24 hours to obtain 26g of Zoledronic acid crystal form XVIII (MS-507-CROP II, LOD by TGA=1. 0%). The overall yield of the process is 50% purity by HPLC 97.7%.
According to the analysis of related databases, 22884-10-2, the application of this compound in the production field has become more and more popular.
Reference:
Patent; TEVA PHARMACEUTICAL INDUSTRIES LTD.; TEVA PHARMACEUTICALS USA, INC.; WO2005/5447; (2005); A2;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem