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【结 构 式】 
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【药物名称】Landiolol, Ono-1101, Onoact 【化学名称】(-)-3-[4-[2(S)-Hydroxy-3-[2-(morpholinocarboxamido)ethylamino]propoxy]phenyl]propionic acid 2,2-dimethyl-1,3-dioxolan-4(S)-yl ester 【CA登记号】133242-30-5, 144481-98-1 (monoHCl), 133242-62-3 (undefined isomer) 【 分 子 式 】C25H39N3O8 【 分 子 量 】509.60488 |
【开发单位】Ono (Originator) 【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS, beta1-Adrenoceptor Antagonists |
合成路线1
Reaction of 3-(4-hydroxyphenyl)propionic acid (I) with the chiral dioxolanylmethyl chloride (II) afforded the corresponding dioxolanylmethyl ester (III). The phenolic hydroxyl group of (III) was then alkylated with (S)-bromohydrin (IV) to produce the intermediate (V).
| 【1】 Iguchi, S.; Kawamura, M.; Miyamoto, T. (Ono Pharmaceutical Co., Ltd.); Novel esters of phenylalkanoic acid. EP 0397031; JP 1991072475; JP 1994073044; US 5013734 . |
| 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) | 25691 | 3-(4-hydroxyphenyl)propionic acid | 501-97-3 | C9H10O3 | 详情 | 详情 |
| (II) | 45778 | (4S)-4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane | 60456-22-6 | C6H11ClO2 | 详情 | 详情 |
| (III) | 48332 | [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-(4-hydroxyphenyl)propanoate | C15H20O5 | 详情 | 详情 | |
| (IV) | 48333 | (2S)-2-(bromomethyl)oxirane | C3H5BrO | 详情 | 详情 | |
| (V) | 48334 | [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-[4-[(2S)oxiranylmethoxy]phenyl]propanoate | C18H24O6 | 详情 | 详情 |
合成路线2
Morpholine (VI) was treated with carbonyl diimidazole (VII), and the resulting imidazolide (VIII) was further condensed with ethylenediamine (IX) to give urea (X). Reaction of epoxide (V) with amine (X) furnished the title compound.
| 【1】 Iguchi, S.; Kawamura, M.; Miyamoto, T. (Ono Pharmaceutical Co., Ltd.); Novel esters of phenylalkanoic acid. EP 0397031; JP 1991072475; JP 1994073044; US 5013734 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 48334 | [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-[4-[(2S)oxiranylmethoxy]phenyl]propanoate | C18H24O6 | 详情 | 详情 | |
| (VI) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (VII) | 11353 | 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) | 530-62-1 | C7H6N4O | 详情 | 详情 |
| (VIII) | 48336 | 1H-imidazol-1-yl(4-morpholinyl)methanone | C8H11N3O2 | 详情 | 详情 | |
| (IX) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (X) | 32153 | N-(2-aminoethyl)-4-morpholinecarboxamide; 4-[N-(2-Aminoethyl)carbamoyl]morpholine | C7H15N3O2 | 详情 | 详情 |