摘要
以4-氯-3-磺胺基苯甲酸和2,3-二氢-2-甲基-1H-吲哚为主要原料,经3步反应合成了降压药吲哒帕胺。4-氯-3-磺胺基苯甲酸与氯化亚砜反应得4-氯-3-磺胺基苯甲酰氯(Ⅰ),产率98.0%;2,3-二氢-2-甲基-1H-吲哚与亚硝酸反应得到N-亚硝基-2,3-二氢-2-甲基-1H-吲哚(Ⅱ),不用分离出Ⅱ,直接用钯/碳催化剂催化氢化得到N-氨基-2,3-二氢-2-甲基-1H-吲哚(Ⅲ),再进一步制成N-氨基-2,3-二氢-2-甲基-1H-吲哚盐酸盐(Ⅳ),产率92.0%;Ⅰ和Ⅳ反应得到目标产物吲哒帕胺(Ⅴ),产率92.5%,所得产品符合药典标准。
Indapamide（ V ） was prepared by three step reactions, starting from 4-chloro-3 sulphamoyl benzoic acid and 2,3-dihydro-2-methyl-lH-indole. 4-Chloro 3-sulphamoyl benzoylchloride（ Ⅰ ） was prepared by the reaction of 4 chloro-3-sulphamoyl benzoic acid and thionylchloride, yield 98.0%. 2,3-Dihydro-2-methyl-lH in- dole was reacted with nitrous acid to give N-nitroso-2,3-dihydro-2-methyl-lH-indole（ Ⅱ ）, which was reduced directly into N-amino-2,3-dihydro 2-methyl 1H-indole（ Ⅲ ） by palladium black catalytic hydrogenation without isolation. N-Amino-2,3-dihydro-2-methyl-lH-indole hydrochloride（Ⅳ） was given by the reaction of Ⅲ and hydrochloride gas, yield 92.0%. Ⅰ was reacted with Ⅳ to give the title compound indapamide（Ⅴ）, yield 92.5%. The V meets the require of the United States Pharmacopoeia ⅩⅩⅠⅩ.
出处
《化学与生物工程》
CAS
2007年第2期22-24,共3页
Chemistry & Bioengineering
关键词
吲哒帕胺
合成
纯化
indapamide
synthesis
purification
