盐酸氯卡色林有关物质的合成

Synthesis of the Related Substances of Lorcaserin Hydrochloride

为控制盐酸氯卡色林的质量,制备了5个有关物质:8-氯-3-(2-氯丙基)-1-甲基-2,3,4,5-四氢-1H-苯并氮杂䓬(A)、(R)-8-氯-1-甲基-3-乙酰基-1,2,4,5-四氢-1H-苯并氮杂䓬(B)、(S)-8-氯-1-甲基-2,3,4,5-四氢-1H-苯并氮杂䓬(2S,3S)-2,3-二羟基丁二酸盐(2∶1)(C)、(R)-7-氯-1-甲基-2,3,4,5-四氢-1H-苯并氮杂䓬盐酸盐(D)、(S)-7-氯-1-甲基-2,3,4,5-四氢-1H-苯并氮杂䓬盐酸盐(E)。其中有关物质A、D和E未见文献报道。产物结构均经1H NMR和MS确证,且有关物质D中氯原子的位置和手性构型经单晶X射线衍射确证,可作为盐酸氯卡色林质量研究的对照物。

To perform the quality control of lorcaserin hydrochloride,five related substances were prepared.These substances were 8-chloro-3-(2-chloropropyl)-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine(A),(R)-8-chloro-1-methyl-3-acetyl-1,2,4,5-tetrahydro-1H-benzo[d]azepine(B),(S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]-azepine(2S,3S)-2,3-dihydroxysuccinate(2∶1)(C),(R)-7-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride(D),(S)-7-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride(E).The related substances A,D and E have not been reported in literature.The structures of the above related substances were confirmed by 1H NMR and MS,and the substitution position of chlorine atom as well as chiral configuration of related substance D was confirmed by single crystal X-ray diffraction,which could be used as references of lorcaserin hydrochloride quality control.