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【结 构 式】

【药物名称】Solpecainol hydrochloride, EGYT-2936

【化学名称】(±)-[1R*,2S*(S*)]-2-[(1-Methyl-2-phenoxyethyl)amino]-1-phenyl-1,3-propanediol hydrochloride
      (±)-threo-2-(1-Methyl-2-phenoxyethylamino)-1-phenyl-1,3-propanediol hydrochloride

【CA登记号】68567-30-6 (free base), 97931-82-3 (free base, non-specified stereoch.), 97058-89-4 (undefined stereoch.)

【 分 子 式 】C18H24ClNO3

【 分 子 量 】337.84988

【开发单位】Egis (Originator)

【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS

合成路线1

2-Aminoacetophenone.HCl (IV) is prepared from acetophenone (I) via 2-bromoacetophenone (II) and the quaternary urotropine salt (III). Acetylation of (IV) with acetic anhydride in water in the presence of sodium hydrogen carbonate yields 2-acetamidoacetophenone (V), which is converted to 2-acetamido-3-hydroxypropiophenone.HCl (VI) with formaldehyde in water. After removing the acetyl group with hydrochloric acid in ethanol, 2-amino-3-hydroxypropiophenone.HCl (VII) is formed, which is reduced with hydrogen over Pd/C in methanol to rac-erythro-2-amino-1-phenyl-1,3-propanediol.HCl (VIII). Reductive condensation of the corresponding base (IX) with phenoxyacetone (X) and hydrogen over PtO2 affords a mixture of aminodiols epimeric at C-1' (XI). (XI) is finally converted to the corresponding hydrochloride salts, from which the salt of the less soluble [1R*,2S*(S*)]-stereoisomer, i.e., solpecainol is isolated by crystallization. Structure and purity of solpecainol have been confirmed by x-ray crystallography and HPLC-MS.

1 Central Res. Inst. Chem. Hung. Acad. Sci. Report (27.10.1983) 1983.
2 Levai, L.; Fazekas, G.; Petocz, L.; Grasser, K. (Egis Pharmaceuticals Ltd.); Novel N-alkyl derivs. of 1-phenyl-2-amino-1,3-propandiol and process for preparing same. DE 2810482; GB 1560470; JP 1978112827; US 4259257 .
3 Vida, L.; Szepesy, L.; Lakszner, K.; Comparison and evaluation of derivatization methods for gas chromatographic determination of various propanediols. Chromatographia 1984, 19, 304.
4 Berényi, E.; Petócz, L.; Blaskó, G.; Nógrádi, M.; Solpecainol Hydrochloride. Drugs Fut 1991, 16, 6, 514.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
34873 1,3,5,7-tetraazatricyclo[3.3.1.1(3,7)]decane 100-97-0 C6H12N4 详情 详情
(I) 10317 Acetophenone 98-86-2 C8H8O 详情 详情
(II) 10315 2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone 70-11-1 C8H7BrO 详情 详情
(III) 14599 2-(1-bromo-1lambda(5),3,5,7-tetraazatricyclo[3.3.1.1(3,7)]dec-1-yl)-1-phenyl-1-ethanone C14H19BrN4O 详情 详情
(IV) 14600 2-(chloroamino)-1-phenylethanone C8H8ClNO 详情 详情
(V) 14601 N-(2-oxo-2-phenylethyl)acetamide C10H11NO2 详情 详情
(VI) 14602 N-[1-(hydroxymethyl)-2-oxo-2-phenylethyl]acetamide C11H13NO3 详情 详情
(VII) 14603 2-(Cloroamino)-3-hydroxy-1-phenyl-1-propanone C9H10ClNO2 详情 详情
(VIII) 14604 (1R,2S)-2-(Chloroamino)-1-phenylpropane-1,3-diol C9H12ClNO2 详情 详情
(IX) 14605 (1R,2S)-2-amino-1-phenyl-1,3-propanediol C9H13NO2 详情 详情
(X) 10875 1-Phenoxyacetone; 1-Phenoxy-2-propanone 621-87-4 C9H10O2 详情 详情
(XI) 14607 (1R,2S)-2-[(1-methyl-2-phenoxyethyl)amino]-1-phenyl-1,3-propanediol C18H23NO3 详情 详情
Extended Information