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【结 构 式】 
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【药物名称】Lanperisone hydrochloride, NK-433 【化学名称】(-)-2(R)-Methyl-3-(1-pyrrolidinyl)-1-[4-(trifluoromethyl)phenyl]propanone hydrochloride 【CA登记号】116287-13-9, 116287-14-0 (free base) 【 分 子 式 】C15H19ClF3NO 【 分 子 量 】321.77298 |
【开发单位】Nippon Kayaku (Originator) 【药理作用】Antispastic Drugs and Drugs for Muscle Spasms, Muscle Spasms, Drugs for, NEUROLOGIC DRUGS, RENAL-UROLOGIC DRUGS, Smooth Muscle Relaxants, Urinary Incontinence Therapy |
合成路线1
The Grignard reaction of 4-(trifluoromethyl)benzaldehyde (I) with ethylmagnesium bromide in ethyl ether gives 1-[4-(trifluoromethyl)phenyl]-1-propanol (II), which is oxidized with CrO3/H2SO4 yielding 4-(trifluoromethyl)propiophenone (III). The condensation of (III) with pyrrolidine (IV) and paraformaldehyde by means of HCl in refluxing isopropanol affords racemic 2-methyl-3-(1-pyrrolidinyl)propiophenone (V), which is finally submitted to optical resolution with N-acetyl-L-phenylglycine (VI) or D-malic acid (VII) and treated with dry HCl gas.
| 【1】 Kurashige, S.; Izumi, G.; Shiozawa, A.; Narita, K.; Sakitama, K.; Ishikawa, M.; Synthesis and activity of 2-methyl-3-aminopropiophenones as centrally acting muscle relaxants. Eur J Med Chem 1995, 30, 1, 85-94. |
| 【2】 Wroblewskki, T.; Castaner, J.; Leeson, P.; Lanperisone Hydrochloride. Drugs Fut 1998, 23, 5, 485. |
| 【3】 Shiozawa, A.; Ishikawa, M.; Sugimura, H.; Yamamoto, H.; Sakasai, T.; Ohtsuki, K.; Kurashige, S. (Nippon Kayaku Co., Ltd.); An optically active propanone deriv. and process for producing the same and use thereof. EP 0266577; JP 1989131171 . |
| 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) | 13380 | 4-(Trifluoromethyl)benzaldehyde; alpha,alpha,alpha-Trifluoro-p-tolualdehyde | 455-19-6 | C8H5F3O | 详情 | 详情 |
| (II) | 13381 | 1-[4-(Trifluoromethyl)phenyl]-1-propanol | C10H11F3O | 详情 | 详情 | |
| (III) | 13382 | 1-[4-(Trifluoromethyl)phenyl]-1-propanone; 4-(Trifluoromethyl)propiophenone | 711-33-1 | C10H9F3O | 详情 | 详情 |
| (IV) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (V) | 13384 | 2-Methyl-3-(1-pyrrolidinyl)-1-[4-(trifluoromethyl)phenyl]-1-propanone | C15H18F3NO | 详情 | 详情 | |
| (VI) | 13385 | (2S)-2-(Acetamido)-2-phenylethanoic acid | C10H11NO3 | 详情 | 详情 |