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【结 构 式】 
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【药物名称】 【化学名称】4-Chloro-N-[2-[3-[1-(4-pyridyl)-4-piperidinylmethyl]ureido]phenyl]benzamide 【CA登记号】219491-38-0 【 分 子 式 】C25H26ClN5O2 【 分 子 量 】463.97127 |
【开发单位】Lilly (Originator) 【药理作用】Anticoagulants, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Coagulation Factor Xa Inhibitors |
合成路线1
Reduction of ethyl ester (I) with LiAlH4 provides primary carbinol (II), which is then converted into amine (III) by Mitsunobu reaction with phthalimide (A) in the presence of PPh3 and DEAD in THF, followed by an hydrazine mediated deprotection in EtOH. Reaction of amine (III) with 2-nitrophenyl isocyanate (IV) in CHCl3/THF or CH2Cl2, followed by reduction of the nitro group by hydrogenation over Pd/C in EtOH, affords aniline (V). Finally, aniline (V) is condensed with acid chloride (VI) in CHCl3 in the presence of pyridine to furnish the target compound.
| 【1】 Tinsley, J.M.; Franciskoich, J.B.; Masters, J.J.; et al.; Non-amidine-containing 1,2-dibezamidobenzene inhibitors of human factor Xa with potent anticoagulant and antithrombotic activity. J Med Chem 2000, 43, 11, 2087. |
| 【2】 Antithrombotic agents. WO 9900121 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 12376 | Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione | 85-41-6 | C8H5NO2 | 详情 | 详情 |
| (I) | 44838 | ethyl 1-(4-pyridinyl)-4-piperidinecarboxylate | C13H18N2O2 | 详情 | 详情 | |
| (II) | 44839 | 1-(4-pyridinyl)-4-piperidinyl hydroperoxide | C10H14N2O2 | 详情 | 详情 | |
| (III) | 44840 | O-[1-(4-pyridinyl)-4-piperidinyl]hydroxylamine; 4-(aminooxy)-1-(4-pyridinyl)piperidine | C10H15N3O | 详情 | 详情 | |
| (IV) | 32771 | 1-isocyanato-2-nitrobenzene; 2-nitrophenyl isocyanate | 3320-86-3 | C7H4N2O3 | 详情 | 详情 |
| (V) | 44841 | N-(2-aminophenyl)-N'-[[1-(4-pyridinyl)-4-piperidinyl]oxy]urea | C17H21N5O2 | 详情 | 详情 | |
| (VI) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |