Alendronate monosodium trihydrate

White Crystalline SolidChEBI: A hydride that is the trihydrate of alendronate sodium

All chemicals were commercially purchased from Sigma Aldrich and used without further purification. Sodium carbonate, NaPreparation of alendronic acid monosodium salt; A mixture of 4-amino-butyric acid (10. Og, 0.097mol) and phosphorous acid (15.9g, 0.194mol) in acetonitrile (150ml) was heated at a temperature of 55-65°C and phosphorous trichloride (26.6g, 0.194mol) was added slowly under stirring. After completion of the addition, the reaction temperature was raised to 70-75Step 1: A mixture of 4-amino-butyric acid (10.0 g, 0.097 mol) and phosphorous acid (15.9 g, 0.194 mol) in acetonitrile (150 ml) was heated at a temperature of 55-65° C. and phosphorous trichloride (26.6 g, 0.194 mol) was added slowly under stirring. After completion of the addition, the reaction temperature was raised to 70-75° C. and the reaction continued for 6-9 hours at the same temperature. The reaction mixture was cooled to 60-65° C. and water (150 ml) was added slowly at the same temperature. The reaction temperature was then increased to 90-100° C. and maintained for the next 4-6 hours. The reaction mixture was then cooled to 55-65° C. and the reaction mixture pH was adjusted to 4.4-4.8 with sodium hydroxide solution. The reaction mixture was cooled to 25-35° C. and the aqueous layer containing the product was separated from the upper acetonitrile layer. The aqueous layer was cooled to and maintained at 0-5° C. for 3 hours. The solid product was separated by filtration and washed with water and finally with methanol to obtain sodium alendronate. The product was dried in a vacuum oven at 45-50° C. until loss on drying was less than 0.5percent w/w. Yield: 16 g (69.6percent). Appearance: almost white powder. Melting range: 234-238° C. (with decomposition).2.6 g (0.025 mol) of -γaminobutyric acid and 6.2 g (0.075mol) of phosphorous acid was added into 6.8 mL of MSA on stirring. Then 7.0 mL (0.075 mol) of phosphoryl chloride was added dropwise in ca. 15 min, and the contents of the flask were stirred at 75°C for 12 h. After cooling the mixture to 26°C, 19 mL (1.1 mol) of water was added and the mixture was stirred further at 105°C for 4 h. The pH was adjusted to 1.8 by adding ~12 mL of 50percent aqueous sodium hydroxide to the mixture. Then, the mixture was stirred at room temperature for 2 h and the precipitate was removed by filtration. The crude product was suspended in 50 mL ofwater and the mixture was stirred at 100°C for 1 h, then the pH was adjusted to 4, 5. After cooling the mixture to 26°C, the solid product was filtered off to give 5.0 g (60percent) of sodium alendronate trihydrate (8) in a purity of 97percent.3.8 mmol (1 equiv) of the respective carboxylic acid (658 mg 3-pyridylacetic acid hydrochloride for 1, 478 mg imidazol-1-yl-acetic acid for 2, 339 mg β-alanine for 3, 392 mg γ-aminobutyric acid for 4, 499 mg 6-aminohexanoic acid for 5) were added to 11.4 mmol (3 equiv) HTo a 250 ml reaction vessel equipped with a water condenser, 8.5 gm (0.1 mol) pyrrolidone, and 33.5 ml water was added under nitrogen atmosphere. Then, 17.2 gm (0.125 mol) PCl To a 250 ml reaction vessel equipped with water condenser, 8.5 gm (0.1 mol) pyrrolidone, and 33.5 ml water was added under nitrogen atmosphere. Then 17.2 gm (0.125 mol) PCl In a 250 reaction vessel equipped with water condenser, 8.5 gm (0.1 mol) pyrrolidone, 14 ml water and 11.5 gm methane sulphonic acid was added under nitrogen atmosphere. At room temperature 17.2 gm (11 ml, 0.125 mol) PClIn a 250 reaction vessel equipped with a water condenser, 8.5 gm (0.1 mol) pyrrolidone, 14 ml water, and 11.5 gm methane sulphonic acid were added under a nitrogen atmosphere. At room temperature, 17.2 gm (11 ml, 0.125 mol) PClExample 3 In a reaction vessel, 17.0 g(0.2 mol) pyrrolidone, 22 ml water and 23 gm methane sulphonic acid were taken and was heated to reflux (105 °C) for 9 hours or till the disappearance of pyrrolidone (monitored by TLC method). The mass was cooled to room temperature and PCl3 (17.5 ml, 0.199 mol) was added drop-wise while maintaining the temperature below 65 °C. Further the reaction was stirred at 60-65 °C for 30 minutes and then the temperature was raised to 110 °C, water was continuously distilled under vacuum. The mass was then cooled to 60 °C and added a further quantity of 90.39 gm (57.5 ml, 0.6565 mol) PCl3 was added drop-wise while maintaining the temperature below 60 °C followed by 25.5 ml of HEXAMPLE 3 In a reaction vessel, 17.0 g (0.2 mol) pyrrolidone, 22 ml water, and 23 gm methane sulphonic acid were mixed and then heated to reflux (i.e., 105° C.) for 9 hours or till the disappearance of pyrrolidone was observed (monitored by TLC method). The mass was then cooled to room temperature and PCl

Alendronate is suitable for the treatment of osteoporosis in postmenopausal women, to prevent hip and spine fractures (vertebral compression fractures), and for osteoporosis in men to increase bone mass.