盐酸阿洛司琼的合成工艺改进

Improvement on the synthetic process of alosetron hydrochloride

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经脱羧制得 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 2 3 7%。经IR、UV、1 H NMR、1 3 C

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.