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【结 构 式】 
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【药物名称】Carvedilol, SK&F-105517, DQ-2466, BM-14190, Coreg CR, Querto, Dibloc, Coropress, Eucardic, Coreg, Artist, Dimitone, Dilatrend, Kredex 【化学名称】1-(9H-Carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]-2-propanol 【CA登记号】72956-09-3 【 分 子 式 】C24H26N2O4 【 分 子 量 】406.48582 |
【开发单位】Roche (Originator), Altana Pharma (Not Determined), Biovail (Licensee), Daiichi Pharmaceutical (Licensee), GlaxoSmithKline (Licensee) 【药理作用】Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Heart Failure Therapy, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, beta1-Adrenoceptor Antagonists |
合成路线1
By condensation of 4-(2,3-epoxypropoxy)carbazole (I) with 2-(2-methoxyphenoxy)ethylamine (II) at 70 C in diglime.
| 【1】 Wiedemann, F.; Kampe, W.; Thiel, M.; Sponer, G.; Roesch, E.; Dietmann, H. (Roche Diagnostics GmbH); Carbazolyl-(4)-oxypropanolamine compounds and therapeutic compositions. DE 2815926; EP 0004920; ES 479396; JP 54157558; US 4503067 . |
| 【2】 Aronhime, J.; Dolitzky, B.-Z.; Finogueev, S.; Kor, I.; Ben-Valid, S.; Hildesheim, J. (Teva Pharmaceutical Industries Ltd.; Teva Pharmaceuticals USA, Inc.); Carvedilol. WO 0200216 . |
| 【3】 Grau, M.; Serradell, M.N.; Castaner, J.; Blancafort, P.; BM-14,190. Drugs Fut 1983, 8, 10, 841. |
合成路线2
This compound has been obtained in two related ways: 1. The reaction of 2-(2-bromoethoxy)anisole (I) with benzylamine (II) by heating at 80 C gives the secondary amine (III), which is condensed with epichlorohydrin (IV) by heating at 60 C to yield the isopropanol derivative (V). The condensation of (V) with 4-hydroxycarbazole (VI) by means of K2CO3 in refluxing dioxane affords the adduct (VII), which is finally debenzylated by hydrogenolysis with H2 over Pd/C in ethanol/water. 2. The condensation of the secondary amine (III) with 4-(2,3-epoxypropoxy)carbazole (VIII) in refluxing ethanol gives the already reported adduct (VII), which is debenzylated as indicated.
| 【1】 Seres, P.; Cselenyak, J.; Nagy, K.; Simig, G.; Gregor, T.; Nagy, P.K.; Greff, Z.; Balazs, L.; Barkoczy, J.; Vereczkey, G.D.; Nemeth, N.; Szabo, T.; Ratkai, Z.; Doman, I. (Egis Pharmaceuticals Ltd.); Process and intermediates for preparing 1-[9'H-carbazol-4'-yloxy]-3-[2''-(2'''-methoxy-phenoxy)ethyl]amino]-propan-2-ol (carvedilol). EP 0918055 . |
| 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) | 51402 | 2-(2-Bromoethoxy)methoxybenzene; 1-Bromo-2-(2-methoxyphenoxy)ethane | 4463-59-6 | C9H11BrO2 | 详情 | 详情 |
| (II) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (III) | 30528 | N-benzyl-2-(2-methoxyphenoxy)-1-ethanamine; N-benzyl-N-[2-(2-methoxyphenoxy)ethyl]amine | C16H19NO2 | 详情 | 详情 | |
| (IV) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (V) | 51403 | 1-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-3-chloro-2-propanol | C19H24ClNO3 | 详情 | 详情 | |
| (VI) | 29480 | 4-Hydroxycarbazole; 9H-carbazol-4-ol | 52602-39-8 | C12H9NO | 详情 | 详情 |
| (VII) | 51404 | 1-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-3-(9H-carbazol-4-yloxy)-2-propanol | C31H32N2O4 | 详情 | 详情 | |
| (VIII) | 40171 | 9H-carbazol-4-yl 2-oxiranylmethyl ether; 4-(2-oxiranylmethoxy)-9H-carbazole | 51997-51-4 | C15H13NO2 | 详情 | 详情 |