CAS: 1210348-34-7; Tert-Butyl ((1R,2S,5S)-2-Amino-5-(Dimethylcarbamoyl)Cyclohexyl)Carbamate Oxalate

相似化合物

365998-36-3 2803419-90-9 2703724-30-3

3-环己烯-1-甲酸置于n-甲基吗啉,吡啶,1,3-二溴-5,5-二甲基海因,氨,水,三乙胺,Potassium Hydroxide,Sodium Hydroxide体系中,用 Aq. Phosphate Buffer,水,二甲基亚砜,乙腈 用作溶剂,化学反应 58.0H,反应生成依度沙班杂质a
参考文献:开发一种高效的合成依多沙班关键中间体的生产工艺
标题:开发一种高效的合成依多沙班关键中间体的生产工艺
摘要:我们报告了一种新型合成方法的开发,该方法可用于合成edoxaban的关键中间体.新的合成方法的主要特征是对关键手性溴内酯的合成方法进行了改进,利用邻近基团的参与进行有趣的环化反应以构建差异保护的1,2-顺式-二胺以及应用了塞子技术-流反应器技术可使不稳定的中间体反应成几百公斤规模.通过实施这些更改,可明显提高制备依多沙班的总产量,并导致更高效,更环保的生产过程.
Doi:10.1021/acs.Oprd.8B00413

专利信息

专利号:US-2015239909-A1
优先权日:2012-11-23
标 题 :Process for the preparation of (1s,4s,5s)-4-bromo-6-oxabicyclo[3.2.1]octan-7-one
发明人：NAKAMURA YOSHITAKA; MUKESH Kumar Madhra; INAMDAR MURAD ISMAIL
权利人:DAIICHI SANKYO CO LTD
摘要:The present invention relates to an improved and industrially advantageous process for the preparation of (1S, 4S, 5S)-4-bromo-6-oxabicyclo[3.2.1]octan-7-one represented by the following formula (1) n n n n n n n n n n which is a key intermediate in the synthesis of edoxaban, a compound that exhibits on inhibitory effect on activated blood coagulation factor X (also referred to as activated factor X or FXa), and is useful as a preventive and/or therapeutic drug for thrombotic diseases. The process includes reacting (1S)-cyclohex-3-ene-1-carboxylic acid of formula (II) with a brominating agent selected from the group consisting of N-bromosuccinimide or 1,3-dibromo-5, 5-dimethylhydantoin in the presence of a base selected from calcium oxide or calcium hydroxide in a solvent selected from the group comprising of dicholoromethane, toluene, tetrahydrofuran, ethyl acetate, hexanes, cyclopentyl methyl ether (CPME) or a misture thereof to get (1S, 4S 5S)-4-bromo-6-oxabicyclo[3.2.1]octan-y-one of formula (1)