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【结 构 式】 
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【药物名称】Clodronate disodium, KCO-692, Cl2MDP, Lytos, Ostac, Clastoban, Loron, Clasteon, Bonefos 【化学名称】(Dichloromethylene)bis(phosphonic acid) disodium salt 【CA登记号】10596-23-3 (free acid) 【 分 子 式 】CH2Cl2Na2O6P2 【 分 子 量 】288.85669 |
【开发单位】Gentili (Originator), Leiras (Originator), Procter & Gamble (Originator), Abiogen (Not Determined), Aventis Pharma (Licensee), Kissei (Licensee), Roche (Licensee) 【药理作用】Antiarthritic Drugs, Bone Cancer Therapy, Bone Diseases, Treatment of, METABOLIC DRUGS, Oncolytic Drugs, Osteoarthritis, Treatment of, Treatment of Hypercalcemia, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, Treatment of Osteoporosis, Bisphosphonates |
合成路线1
The reaction of dibromomethane (I) with triisopropylphosphite (II) at 145 C gives tetraisopropyl methylenediphosphonate (III), which is treated first with sodium and then with chlorine to give the compound (IV). This compound is finally hydrolyzed with refluxing concentrated HCl, or treated with refluxing tetrachloroethane.
| 【1】 Nicholson, D.A.; Prentice, J.B.; Quimby, O.T.; Tetrasodium carbonyldiphosphonate. Synthesis reactions and spectral properties. J Org Chem 1967, 32, 12, 4111-14. |
| 【2】 Roy, C.H.; Substituted methylene diphosphonic acids and their salts. NL 6514133 . |
| 【3】 Roy, C.H. (The Procter & Gamble Co.); Substituted methylene diphosphonic acids and their salts. BE 0672205; DE 1793768; FR 1457272; GB 1026366; US 3404178; US 3422021 . |
| 【4】 Castaner, J.; Hopkins, S.J.; Blancafort, P.; Serradell, M.N.; Clodronate disodium. Drugs Fut 1982, 7, 9, 615. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 32163 | Dibromomethane | 74-95-3 | CH2Br2 | 详情 | 详情 |
| (II) | 32162 | Triisopropyl phosphite | 116-17-6 | C9H21O3P | 详情 | 详情 |
| (III) | 27980 | Diisopropyl (diisopropoxyphosphoryl)methylphosphonate; Tetraisopropyl methylenediphosphonate | 1660-95-3 | C13H30O6P2 | 详情 | 详情 |
| (IV) | 32164 | diisopropyl dichloro(diisopropoxyphosphoryl)methylphosphonate | C13H28Cl2O6P2 | 详情 | 详情 |