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【结 构 式】 
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【药物名称】 【化学名称】4-[4-[N-[3-(5-Amidino-2-hydroxyphenyl)-2(E)-propenyl)carbamoyl]phenyl]pyridine-2-carboxamide 【CA登记号】 【 分 子 式 】C23H21N5O3 【 分 子 量 】415.45552 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Anticoagulants, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Coagulation Factor Xa Inhibitors |
合成路线1
The intermediate pyridylbenzoic acid (III) was prepared by treatment of pyridine-N-oxide (I) with trimethylsilyl cyanide, followed by acid hydrolysis of the cyano and ester groups
| 【1】 Pauls, H.W.; Brown, K.D.; Liang, G.; Czekaj, M.; Chu, V.; Spada, A.P.; Gong, Y.; Gao, J.; Colussi, D.J.; Amido-(propyl and allyl)-hydroxybenzamidines: Development of achiral inhibitors of factor Xa. Bioorg Med Chem Lett 2000, 10, 3, 217. |
合成路线2
3-Bromo-4-hydroxybenzonitrile (IV) was protected as the methoxymethyl ether (V). Subsequent Heck reaction with N-allyl phthalimide (VI) produced adduct (VII). The phthaloyl group OF (VII) was then removed by hydrazinolysis to yield the primary amine (VIII), which was coupled with carboxylic acid (III) using TBTU to afford amide (IX). Pinner reaction of (IX) with concomitant methoxymethyl group deprotection gave imidate (X). Finally, ammonolysis of the imidate group of (X) furnished the title amidine.
| 【1】 Pauls, H.W.; Brown, K.D.; Liang, G.; Czekaj, M.; Chu, V.; Spada, A.P.; Gong, Y.; Gao, J.; Colussi, D.J.; Amido-(propyl and allyl)-hydroxybenzamidines: Development of achiral inhibitors of factor Xa. Bioorg Med Chem Lett 2000, 10, 3, 217. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 46461 | 4-[2-(aminocarbonyl)-4-pyridinyl]benzoic acid | C13H10N2O3 | 详情 | 详情 | |
| (IV) | 46462 | 3-bromo-4-hydroxybenzonitrile | 2315-86-8 | C7H4BrNO | 详情 | 详情 |
| (V) | 46463 | 3-bromo-4-(methoxymethoxy)benzonitrile | C9H8BrNO2 | 详情 | 详情 | |
| (VI) | 46464 | 2-allyl-1H-isoindole-1,3(2H)-dione | C11H9NO2 | 详情 | 详情 | |
| (VII) | 46465 | 3-[(E)-3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-propenyl]-4-(methoxymethoxy)benzonitrile | C20H16N2O4 | 详情 | 详情 | |
| (VIII) | 46466 | 3-[(E)-3-amino-1-propenyl]-4-(methoxymethoxy)benzonitrile | C12H14N2O2 | 详情 | 详情 | |
| (IX) | 46467 | 4-[4-[([(E)-3-[5-cyano-2-(methoxymethoxy)phenyl]-2-propenyl]amino)carbonyl]phenyl]-2-pyridinecarboxamide | C25H22N4O4 | 详情 | 详情 | |
| (X) | 46468 | ethyl 3-[(E)-3-([4-[2-(aminocarbonyl)-4-pyridinyl]benzoyl]amino)-1-propenyl]-4-hydroxybenzenecarboximidoate | C25H24N4O4 | 详情 | 详情 |