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【结 构 式】 
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【药物名称】Nafoxidine hydrochloride 【化学名称】1-[2-[p-(3,4-dihydro-6-methoxy-2-phenyl-1-naphthyl)phenoxy]ethyl]pyrrolidine hydrochloride 【CA登记号】1845-11-0 (free base) 【 分 子 式 】C29H32ClNO2 【 分 子 量 】462.03689 |
【开发单位】Pfizer (Originator) 【药理作用】Breast Cancer Therapy, Oncolytic Drugs, Antiestrogens |
合成路线1
The condensation of 3-methoxyacetophenone (I) with benzaldehyde (II) by means of NaOH in ethanol - water gives 3'-methoxychalcone (III), which by addition of HCN (KCN) in ethanol-acetic acid is transformed into 2-phenyl-4-(3-methoxyphenyl)-4-oxobutyronitrile (IV). The hydrolysis of (IV) with aqueous H2SO4 at 100 C affords the corresponding ketoacid (V), which is reduced with amalgamated zinc and 2N HCl yielding 2-phenyl-4-(3-methoxyphenyl)butyric acid (VI). The cyclization of (VI) by means of liquid HF yields 2-phenyl-6-methoxy-1,2,3,4-tetrahydro-1-naphthalenone (VII), which is finally condensed with 4-(2-pyrrolidinoethoxy)phenylmagnesium bromide in refluxing THF.
| 【1】 Thorpe, P.; Castañer, J.; Nafoxidine. Drugs Fut 1978, 3, 3, 211. |
| 【2】 Duncan, G.W.; Lednicer, D.; US 3483293 . |
| 【3】 Lednicer, D.; US 3274213 . |
| 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) | 18792 | 3-methoxyacetophenone; 1-(3-methoxyphenyl)-1-ethanone | 586-37-8 | C9H10O2 | 详情 | 详情 |
| (II) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (III) | 39791 | (E)-1-(3-methoxyphenyl)-3-phenyl-2-propen-1-one | C16H14O2 | 详情 | 详情 | |
| (IV) | 39792 | 4-(3-methoxyphenyl)-4-oxo-2-phenylbutanenitrile | C17H15NO2 | 详情 | 详情 | |
| (V) | 39793 | 4-(3-methoxyphenyl)-4-oxo-2-phenylbutyric acid | C17H16O4 | 详情 | 详情 | |
| (VI) | 39794 | 4-(3-methoxyphenyl)-2-phenylbutyric acid | C17H18O3 | 详情 | 详情 | |
| (VII) | 39795 | 6-methoxy-2-phenyl-3,4-dihydro-1(2H)-naphthalenone | C17H16O2 | 详情 | 详情 | |
| (VIII) | 29184 | bromo[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]magnesium | C12H16BrMgNO | 详情 | 详情 |