盐酸阿洛司琼的合成工艺改进

据文献报道，以3-甲氧甲酰基-2，4-二氧哌啶钠盐（2）为原料，采用两条不同的合成路线，成功地制备了盐酸阿洛司琼（alosetron，1）。路线一以化合物2与1-甲基-1-苯肼硫酸盐缩合得到5，6-二氢-4-(2-甲基-2-苯肼)-2(1H)-吡啶酮（3），再经环合、对接制得盐酸阿洛司琼，总收率为10%。路线二以化合物2经脱竣制得2，4-哌啶二酮（5），与1-甲基-1-苯肼缩合制得3，再经环合、对接制得盐酸阿洛司琼，总收率为23.7%。经IR、UV、^1H-NMR、^13C-NMR及MS测试确证目标化合物结构。

Improvement on the synthetic process of alosetron hydrochloride

Two methods for preparation of alosetron hydrochloride were studied by using a start material 2,4 dioxo 3 piperidinecarboxylic acid,methylester,ion(1 ),sodium(2).1,5,6 Dihydro 4 (2 methyl 2 phenylhydrazino) 2( 1H ) pyridinone(3)was prepared by a one step reaction of 1 methyl 1 phenylhydrazine sulphate with 2,4 dioxo 3 piperidinecarboxylic acid,methylester,ion(1 ),sodium(2).2,5,6 Dihydro 4 (2 methyl 2 phenylhydrazino) 2( 1H ) pyridinone(3)can be obtained through a two step reaction.At first,the start material 3 piperidinecarboxylic acid,2,4 dioxo,methylester,ion(1 ),sodium(2)was decarboxylated to give 2,4 piperidinedione(5)and then reacted with 1 methyl 1 phenylhydrazine.Although there is no difference in the last two steps(cyclization and substitution)of the two methods,but the total yields were 10% and 23 7% respectively in method 1 and method 2.The final product was characterized by IR,UV, 1H NMR, 13 C NMR and MS.