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CAS No. : | 63234-80-0 | MDL No. : | MFCD06200813 |
Formula : | C11H15ClN2O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CMWCQQUYLPYOMY-UHFFFAOYSA-N |
M.W : | 226.70 | Pubchem ID : | 2763079 |
Synonyms : |
|
Chemical Name : | 3-(2-Chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P501-P260-P270-P264-P280-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405 | UN#: | 3261 |
Hazard Statements: | H302-H314 | Packing Group: | Ⅱ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.8% | With sodium carbonate In methanol at 73 - 75℃; for 4 - 4.5 h; | Example 2; Preparation of risperidone of the formula (I) from 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido [ 1,2-a]pyrirnidine-4-one and 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole bases of the formulae (II) and (III).Starting from 11.45 g of 6-fluoro-3-(4-piperidinyl)-l,2-benzisoxazole, 12.45 g of 3-(2-cWoroemyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[l,2-a]pyrimidine-4-one and 11.8 g of dry sodium carbonate the same method as described in Example 1 is followed, to give 19.8 g (92.8 percent) of risperidone.Mp: 171-172 °C; purity is at least 99 percent, determined by HPLC |
77.8% | With N-ethyl-N,N-diisopropylamine In methanol at 45 - 50℃; for 70 - 100 h; | 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (20.0 grams), 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (22.6 grams) and diisopropyl ethylamine (14.1 grams) were dissolved in methanol (90.0 ml). The resulting reaction mixture was maintained at 45-50° C. for about 70-100 hours. The reaction mass was then cooled to 25-35° C. and then separate solid product. The solid mass was filtered and washed with methanol (20.0 ml) followed by water (120.0 ml). The wet product was dried at 70-80° C. to get 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-A]pyrimidin-4-one. (Yield: 29.0 g; 77.8percent; purity by HPLC is 99.93percent)6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (10 Kg), 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (11.3 Kg) and diisopropyl ethylamine (7 Kg) were dissolved in methanol (45 Lt). The resulting reaction mixture was maintained at 45-50° C. for about 70 to 100 hours. The reaction mass was then cooled to 25-35° C. and then separate solid product. The solid mass was filtered and washed with methanol (10 Lt) followed by water (60 Lt). The wet product was dried at 70-80° C. to get 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-A]pyrimidin-4-one. (Yield: 18 Kg, purity by HPLC is 99.93percent). |
73% | With sodium carbonate In water at 85 - 90℃; for 4 h; | [2.27G OF 4- (6-FLUORO-1, 2-BENZISOXAZOL-3-YL) -PIPERIDINE OBTAINED IN STEP A)] and 2.26g of 3- (2-chloroethyl)-6, 7,8, 9-tetrahydro-2-methyl-4H-pyrido [1, 2- [A] PYRIMIDIN-4-ONE] obtained in Preparation Example 2 were added to a solution of 2.25g of [NA2C03] in [12ML] of water. The resulting mixture was stirred at 85 to [90 °C] for 4 hours, cooled to room temperature, and filtered. The resulting solid was added to [16ML] of N, N- dimethylformamide. The resulting suspension was heated to [80 °C,] left at that temperature for 5 minutes, and then slowly cooled to room temperature. The crystal was filtered, washed with [5ML] of water and dried to obtain 3.02g of the title compound as a white crystal (yield: 73percent). The melting point [ANDAPOS;H-NMR] data were the same as in Example 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With potassium hydroxide In water at 120 - 130℃; for 1.5 h; | 2.77g of 2,4-difluorophenyl (4-piperidinyl) methanone oxime hydrochloride obtained in Preparation Example 1 and 2.26g of 3- (2-chloroethyl)- 6,7, 8,9-tetrahydro-2-methyl-4H-pyrido [1, 2-a] pyrimidin-4-one obtained in Preparation Example 2 were added to [27ML] of 30percent aqueous potassium hydroxide, and then the resulting mixture was stirred at 120 to 130°C for 90 minutes. The reaction mixture was cooled to room temperature, filtered, and the obtained solid was added to [16ML] of N, N-dimethylformamide. The resulting suspension was heated to [80 °C,] left at that temperature for 5 minutes, and then slowly cooled to room temperature. The resulting crystal was filtered, washed with 5ml of water and dried to obtain 3.39g of the title compound as a white crystal (yield: 82percent). Melting point: 167-169°C ; Purity: 99.7percent (by HPLC); [H-NMR] [(300MHZ,] [CDC13)] : [6] 7.65-7. 61 (m, 1H), 7.18-7. 14 (m, 1H), 7.00-6. 94 (m, 1H), 3.87-3. 83 (m, 2H), 3.12-3. 07 (m, 2H), 2.97-3. 02 (m, 1H), 2.81-2. 76 (m, 2H), 2.71-2. 66 (m, 2H), 2.48-2. 43 (m, 2H), 2.23 (s, 3H), 2.34-2. 19 (m, 2H), 2.05-2. 01 (m, 4H), 1.87-1. 79 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.2% | With sodium carbonate In water at 110 - 120℃; for 0.666667 h; | Example 9; Preparation of 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (risperidone)In a 50-ml reaction flask, 2.56 g of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride and 2.95 g of 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one are placed, then a sodium carbonate solution or suspension (dissolved or suspended 8.5 g of sodium carbonate in 25 ml water) is added. The mixture is put into heating bath at 110-120° C. with stirring for 40 min, then cooled with continuous stirring to the room temperature and the precipitate solid is filtered, washed with pure water, and dried to give 3.82 g of the product in 93.2percent yield. The product is purified to obtain a purity of 99.5percent (determined by HPLC) with DMF and isopropanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With hydrogenchloride; hydrogen In water at 20℃; for 8 h; | 28g of [3- (2-CHLOROETHYL)-2-METHYL-4H-PYRIDO [1,] 2-a] pyrimidin-4-one obtained in step A) was dissolved in [90ML] of 6N hydrochloric acid, 2.8g of 10percent- palladium was added thereto, and then the mixture was hydrogenated under a hydrogen pressure of 35psi at room temperature for 8 hours. The reaction mixture was filtered through Cellite and the filtrate was concentrated under a reduced pressure, [200ML] of isopropanol was added to the residue, and then the mixture was stirred. The solid was filtered and dried to obtain 25. 1g of the title compound as a white crystal (yield: 90percent). |
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