Letosteine

Diuretic and electrolyte effects of oral tolvaptan tablets in healthy male Chinese volunteers;

口服托伐普坦片对男性健康志愿者的药效学作用及其对血电解质的影响

7-Chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine,the key intermediate of V_2 receptor antagonist tolvaptan was synthesized from 5-chloro-2-nitrobenzoic acid by esterification and reduction to give methyl 2-amino- 5-chlorobenzoate.

5-氯-2-硝基苯甲酸经酯化、还原得到2-氨基-5-氯苯甲酸甲酯,然后经磺酰化、N-烷基化、Dieckmann缩合,再经脱羧、脱磺酸基保护得到V_2受体拮抗剂托伐普坦的关键中间体7-氯-5-氧代-2,3,4,5-四氢-1H-1-苯并氮杂,总收率约37%。