迪拉马尼的合成研究

Synthesis of Delamanid

以β-甲基烯丙醇(4)和4-[4-(三氟甲氧基)苯氧基]哌啶(2)为起始原料,经环化、置换、取代、磺化、缩合5步反应合成新型治疗多重耐药肺结核病药物迪拉马尼(1),反应总产率约43. 7%(以4计算,摩尔收率).目标化合物结构经~1H-NM R和ESI-MS确证,HPLC检测纯度> 98%,ee值> 99%.与文献报道方法比较该合成方法缩短了反应路线,提高了反应总收率,降低了生产成本,且反应条件温和,原料易得,操作简单.

Delamanid, an approved drug for the treatment of multidrug-resistant tuberculosis was synthesized using β-methallyl alcohol 4 and 4- [ 4- （trifluoromethoxy） phenoxy） ] piperidin 2 as starting material by five-step reactions of cyclization, substitution, replacing, sulfonation and condensation. The overall yield of the reaction was about 43.7 % （based on（ -methallyl alcohol）. The structure of compound was verified by 1 H-NMR and ESI-MS,and the purity was over 98 % tested by HPLC, ee. was ever 99 %. This synthetic route is shortened, the yield is improved ,the condition is modest, and the materials are easy to get.