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【结 构 式】 
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【药物名称】Levobunolol hydrochloride, AG-901, AGN-101291-A-L, W-7000A, Mirol, BetaSite(substained-release), Betagan, Vistagan, Gotensin 【化学名称】(-)-5-[3-(tert-Butylamino)-2-hydroxypropoxy]-3,4-dihydro-1(2H)-naphthalenone hydrochloride 【CA登记号】27912-14-7, 47141-42-4 (free base) 【 分 子 式 】C17H26ClNO3 【 分 子 量 】327.85467 |
【开发单位】Allergan (Originator), InSite Vision (Not Determined), Kaken (Marketer), Bausch & Lomb (Licensee), Kyorin (Licensee) 【药理作用】Antiglaucoma Agents, OCULAR MEDICATIONS, Ophthalmic Drugs, beta-Adrenoceptor Antagonists |
合成路线1
The reaction of 5-hydroxy-7-tetralone (I) with epichlorohydrin (I) at reflux temperature gives 5-(3-chloro-2-hydroxypropoxy)-7-tetralone (III), which is then condensed with butylamine (IV) in refluxlng alcohol.
| 【1】 Shavel, J.Jr.; Farber, S. (Pfizer Inc.); 3,4-Dihydroxynaphtalenoneoxy-2-hydroxypropylamines. BE 0739195; DE 1948144; DE 1967162; FR 2018626; GB 1223527; JP 48043734B; US 3641152 . |
| 【2】 Castaner, J.; Serradell, M.N.; Weetman, D.F.; Blancafort, P.; Levobunolol Hydrochloride. Drugs Fut 1983, 8, 9, 788. |
| 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) | 31099 | 5-hydroxy-3,4-dihydro-1(2H)-naphthalenone | 28315-93-7 | C10H10O2 | 详情 | 详情 |
| (II) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (III) | 31100 | 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydro-1(2H)-naphthalenone | C13H15ClO3 | 详情 | 详情 | |
| (IV) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |
合成路线2
It can be obtained in two different ways both starting from the sodium salt of 5-hydroxy-3,4-dihydro-1(2H)-naphthalenone (I): 1) Its condensation with epichlorhydrine (A) in ethanol gives 5-(2,3-epoxypropoxy)-3,4-dihydro-1(2H)-naphthalenone (II), which is then condensed with tert-butylamine (B) in refluxing ethanol. 2) Its condensation with 3-chloro-1,2-propanediol (C) gives 5-(2,3-dihydroxy-propoxy)-3,4-dihydro-1(2H)-naphthalenone (III), which is esterified with tosyl chloride to the sulfonic ester (IV), and finally condensed with tert-butylamine.
| 【1】 Merrill, E.J.; Synthesis of 14C-labeled Bunolol. J Pharm Sci 1971, 60, 10, 1589-91. |
| 【2】 Castaner, J.; Arrigoni-Martelli, E.; Bunolol. Drugs Fut 1976, 1, 9, 403. |
| 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) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (B) | 17895 | 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine | 75-64-9 | C4H11N | 详情 | 详情 |
| (I) | 40456 | sodium 5-oxo-5,6,7,8-tetrahydro-1-naphthalenolate | C10H9NaO2 | 详情 | 详情 | |
| (II) | 40457 | 5-(2-oxiranylmethoxy)-3,4-dihydro-1(2H)-naphthalenone | C13H14O3 | 详情 | 详情 | |
| (III) | 40458 | 5-(2,3-dihydroxypropoxy)-3,4-dihydro-1(2H)-naphthalenone | C13H16O4 | 详情 | 详情 | |
| (IV) | 40459 | 2-hydroxy-3-[(5-oxo-5,6,7,8-tetrahydro-1-naphthalenyl)oxy]propyl 4-methylbenzenesulfonate | C20H22O6S | 详情 | 详情 | |
| (C) | 12975 | 3-Chloro-1,2-propanediol; Glycerol alpha-monochlorohydrin | 96-24-2 | C3H7ClO2 | 详情 | 详情 |