22345-47-7Relevant articles and documents
Synthesis of Tofisopam by Way of Photoinduced CO2 Fixation
Masuda, Yusuke,Makita, Katsuhiko,Ishida, Naoki,Murakami, Masahiro
, p. 4189 - 4192 (2019/11/26)
Herein reported is a unique synthetic route of Tofisopam, an anxiolytic drug containing a 2,3-benzodiazepine core structure. 3,4-Dimethoxypropylbenzene and 3,4-dimethoxybenzoic acid, which are both of plant origin, and CO2 constitute its carbon skeleton. These three renewable substances are united by two C?C bond forming reactions, i.e., a Friedel–Crafts acylation reaction and a photoinduced carboxylation reaction to construct the major carbon framework. Finally, a methyl group is introduced by a Kumada-type cross-coupling reaction to furnish Tofisopam. Various analogs of Tofisopam are readily synthesized by introducing other substituents than a methyl group at the last C?C bond forming step.
Synthesis of 2,3-benzodiazepines and 2,3-benzodiazepin-4-ones from arynes and β-diketones
Okuma, Kentaro,Tanabe, Yukiko,Nagahora, Noriyoshi,Shioji, Kosei
, p. 1064 - 1073 (2015/09/01)
2,3-Benzodiazepines were synthesized by two-step or one-pot reactions from aryne precursors. Reaction of 2- (trimethylsilyl)aryl triflates with β-diketones in the presence of CsF gave ortho-substituted benzophenones. Treatment of benzophenones with hydrazine hydrate resulted in the formation of 2,3-benzodiazepines in moderate yields. Tofisopam, a well known anxiolytic, could be synthesized via C-C bond insertion of 3,4-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)butane-1,3-dione, followed by the reaction with hydrazine hydrate in one-pot operation. 2,3-Benzodiazepin-4-ones were also synthesized by the reaction of β-keto esters with triflates in the presence of CsF, followed by the addition of hydrazine hydrate. Substituted isoquinolines were synthesized by the reaction of ortho-substituted benzophenones with ammonium hydroxide.
One-pot synthesis of 2,3-benzodiazepines from arynes and β-diketones
Okuma, Kentaro,Tanabe, Yukiko,Itoyama, Ryoichi,Nagahora, Noriyoshi,Shioji, Kosei
supporting information, p. 1260 - 1262 (2013/10/22)
Novel one-pot synthesis of 2,3-benzodiazepines from aryne precursors was accomplished. Tofisopam, well-known anxiolytics, could be synthesized via C-C bond insertion of 4,5-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)- butane-1,3-dione, followed by the reaction with hydrazine hydrate in a one-pot operation. This protocol is applicable to the synthesis of other biologically active 2,3-benzodiazepines, such as Girisopam and Nerisopam.
