Statistics shows that 130049-82-0 is playing an increasingly important role. we look forward to future research findings about 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one.
The major producers of chemicals have been the Europe, Japan and China. Due to the growing call for a cleaner, greener environment, people will have to find innovative ways to maintain their relevance. Here is a compound 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. This compound has unique chemical properties. The synthetic route is as follows. 130049-82-0
Example 2 Step-I: Preparation of Crude Paliperidone3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one (25 g) was added to ethanol (500 ml) at 25-30 C. under stirring. 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (20.1 g) and anhydrous sodium carbonate (38 g) were added to the above solution and then heated to 58-62 C. The resulting mass was stirred for 24 hours at 58-62 C. The reaction mass was cooled to 25 C., the inorganic material was filtered out and the resulting mass was washed with ethanol (75 ml). The ethanol was distilled under vacuum in water bath at 50 C. and the resulting residue was dissolved in methylene dichloride (1250 ml). The methylene chloride solution was washed with water (600 ml) 3 times and then dried with anhydrous sodium sulfate. Sodium sulfate was filtered and methylene dichloride was distilled under vacuum at 30-40 C. After complete distillation of methylene chloride, methanol (75 ml) was added to the residue, stirred for 2 hours, filtered the material and dried at 50 C. under high vacuum to yield 23.0 g of crude paliperidone (HPLC Purity: 95.11%; content of the keto impurity: 0.24 wt %).Step-II: Purification of PaliperidoneCrude paliperidone (23 g, obtained in step-I) was heated with dimethylformamide (115 ml) under stirring at 56 C. for 3 hours. The resulting mass was cooled to 25 C., and material was filtered and washed initially with dimethylformamide (23 ml) followed by methanol (23 ml). The resulting solid was heated to 56 C. with dimethylformamide (69 ml) and the mass was stirred for 3 hours and then cooled to 25 C. The resulting mass was filtered and washed initially with dimethylformamide (23 ml) followed by methanol (23 ml). The resulting solid was stirred with methanol (80 ml) for 3 hours, filtered, washed with methanol (80 ml), and then dried in an air oven at 25 C. for 3 hours to yield 13.6 g of paliperidone. The product was then dissolved in methanol (816 ml) at 65 C. to provide a clear solution and the solution was cooled to 50 C. This procedure was followed by the addition of activated carbon (3.5 gm). The resulting mass was stirred for 30 minutes at 50 C. and then filtered on a Hiflo bed. Sodium borohydride (10 mg) was added to the resulting solution and then stirred for 2 hours at 50 C. followed by distillation of methanol until the paliperidone crystallized out. The resulting solution was cooled to 25 C., filtered the material, washed with methanol and then dried at 60 C. under vacuum to yield 10.7 g of pure paliperidone (HPLC Purity: 99.95%; Content of the keto impurity: 0.035 wt %).; Example 4 Purification of PaliperidoneCrude paliperidone (20 g, obtained in step-I of example 2) was heated with sulfolane (100 ml) under stirring at 60 C. for 3 hours, the resulting mass was cooled to 25 C. The material was filtered and washed initially with sulfolane (20 ml) followed by methanol (20 ml). The filtered solid was slurried with sulfolane (60 ml), the resulting slurry was heated to 60 C. under stirring and then maintained for 3 hours. The resulting mass was cooled to 25 C., filtered the solid and washed initially with sulfolane (20 ml) followed by methanol (20 ml). The filtered solid was stirred with water (200 ml) for 1 hour and then the material was filtered and washed with water (100 ml) followed by methanol (50 ml). The resulting solid was then stirred with methanol (100 ml) for 1 hour, and the material was filtered and washed with methanol (50 ml) and then dried in an air oven at 25 C. for 3 hours to yield 13.3 g of paliperidone. The product was then dissolved in methanol (800 ml) at 65 C. to provide a clear solution. The solution was cooled to 50 C. followed by the addition of silica gel (20 g) with stirring for 30 minutes at 50 C. The resulting solution was filtered to remove the silica gel. Sodium borohydride (10 mg) was added to the resulting filtrate and the temperature was maintained for 2 hours at 50 C. Methanol was distilled until paliperidone crystallized out and the resulting solution was cooled to 25 C. The separated solid was filtered, washed with methanol and then dried at 60 C. under vacuum to yield 11 g of pure paliperidone (HPLC Purity 99.7%; Content of the keto impurity at 0.96 RRT: 0.02 wt %).
Statistics shows that 130049-82-0 is playing an increasingly important role. we look forward to future research findings about 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one.
Reference:
Patent; ACTAVIS GROUP PTC EHF; US2009/247553; (2009); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia