With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.130049-82-0, name is 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one, molecular formula is C11H15ClN2O2, molecular weight is 242.7, as common compound, the synthetic route is as follows.HPLC of Formula: C11H15ClN2O2
300 ml of acetonitrile was charged followed by 20.0 g of 3-(2-chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido-[1,2-a]-pyrimidin-4-one and 21.0 g of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride at room temperature. The reaction mass was stirred at room temperature for 5 minutes and 20.0 g of potassium carbonate and 0.7 g of potassium iodide were charged. Further, 0.2 g of sodium borohydride was charged and the temperature was raised to 65±2 C. The reaction mass was maintained at 65±2 C. for 25 hours. After reaction completion, the reaction mass was slowly cooled to room temperature. The solids were filtered, washed with 50 ml of acetonitrile and then dissolved in 800 ml of methylene chloride at room temperature. The contents were heated to 30-35 C., maintained for 10 minutes, filtered and washed with 20 ml of methylene chloride. The clear filtrate was distilled completely under vacuum below 35 C. and replaced with 50 ml of acetone. Further, 300 ml of acetone was charged, heated to 45 C. and stirred for 30 minutes. The reaction mass was cooled to room temperature and stirred for 1 hour. The product was filtered, washed with 20 ml of acetone and dried under vacuum at 50-55 C. to yield paliperidone (30 g, yield: 150% w/w, efficiency: 85.11%, keto impurity by HPLC: 0.01%, total impurity level by HPLC: 1.0%)
At the same time, in my other blogs, there are other synthetic methods of this type of compound,130049-82-0, 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one, and friends who are interested can also refer to it.
Reference:
Patent; CIPLA LIMITED; Puppala, Ravikumar; Pathi, Srinivas Laxminarayan; Kankan, Rajendra Narayanrao; US2014/200228; (2014); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia