- Atom-efficient transition-metal-free arylation ofN,O-acetals using diarylzinc reagents through Zn/Zn cooperativity
-
Exploiting the cooperative action of Lewis acid Zn(C6F5)2with diarylzinc reagents, the efficient arylation ofN,O-acetals to access diarylmethylamines is reported. Reactions take place under mild reaction conditions without the need for transtion-metal catalysis. Mechanistic investigations have revealed that Zn(C6F5)2not only acts as a Lewis acid activator, but also enables the regeneration of nucleophilic ZnAr2species, allowing a limiting 50 mol% to be employed.
- Borys, Andryj M.,Gil-Negrete, Jose M.,Hevia, Eva
-
p. 8905 - 8908
(2021/09/10)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF AN ANTIHISTAMINE AGENT
-
The present invention relates to an improved process for the preparation of an antihistamine agent. The present invention particularly relates to an improved process for the preparation of Cyclizine or its salts. The present invention more particularly relates to an improved process for the preparation of Cyclizine hydrochloride. The present invention further relates to commercially feasible process for the preparation of Cyclizine hydrochloride.
- -
-
Page/Page column 13-14
(2018/02/03)
-
- Continuous-Flow Multistep Synthesis of Cinnarizine, Cyclizine, and a Buclizine Derivative from Bulk Alcohols
-
Cinnarizine, cyclizine, buclizine, and meclizine belong to a family of antihistamines that resemble each other in terms of a 1-diphenylmethylpiperazine moiety. We present the development of a four-step continuous process to generate the final antihistamines from bulk alcohols as the starting compounds. HCl is used to synthesize the intermediate chlorides in a short reaction time and excellent yields. This methodology offers an excellent way to synthesize intermediates to be used in drug synthesis. Inline separation allows the collection of pure products and their immediate consumption in the following steps. Overall isolated yields for cinnarizine, cyclizine, and a buclizine derivative are 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h-1. The incredible bulk: Bulk alcohols are converted continuously into chlorides using HCl in a microflow. A reaction network that consists of four steps and two inline separations leads to the continuous preparation of cinnarizine, cyclizine, and a buclizine derivative with yields of 82, 94, and 87 %, respectively. The total residence time for the four steps is 90 min with a productivity of 2 mmol h-1.
- Borukhova, Svetlana,Nol, Timothy,Hessel, Volker
-
-
- SUBSTITUTED DIBENZHYDRYLPIPERAZINES
-
The present invention relates to new dibenzhydrylpiperazine modulators of histamine receptors, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 26
(2009/07/18)
-
- Synthesis of tertiary amines using a polystyrene (REM) resin
-
A range of tertiary amines was constructed using a 'traceless' linker on a polystyrene resin (REM resin), starting from seconday amines, primary amines, and resin-bound 'ammonia'. The methodology is characterized by three essential steps conducted under ambient conditions: (1) coupling of the starting amine (Michael addition) to the resin, (2) activation (quaternization), and (3) cleavage of the product amine (Hofmann elimination). The linker is compatible with both acid and base sensitive protecting group strategies. The nature of the chemistry ensures that the tertiary amine products are obtained in consistently high purity (95% or greater). After cleavage of the product, REM resin is regenerated and can be reused for repeat syntheses. The yield and purity of repeat batches is maintained over 5 cycles, allowing the automated synthesis of >0.5 g quantities of pure tertiary amine.
- Brown, Angus R.,Rees, David C.,Rankovic, Zoran,Morphy, J. Richard
-
p. 3288 - 3295
(2007/10/03)
-
- Ruthenium Complex Catalyzed N-Heterocyclization. Syntheses of N-Substituted Piperidines, Morpholines, and Piperazines from Amines and 1,5-Diols
-
1,5-Pentanediol reacts with aliphatic and aromatic primary amines in the presence of a ruthenium catalyst modified with phosphonic ligands to give N-substituted piperidines in fair to goods yields.The reactions were carried out at 150-180 deg C for 5 h in dioxane.The nature of the phosphorus ligands has a remarkable effect on the catalytic activity, For the reaction of aromatic amines, triphenylphosphine is effective, while for aliphatic amine more basic tributyl- or triethylphosphine is preferable.Amines also react with diethylene glycol and N-substituted diethanolamines in the presence of the ruthenium catalyst to give N-substituted morpholines and piperazines in good yields, respectively.
- Tsuji, Yasushi,Huh, Keun-Tae,Ohsugi, Yukihiro,Watanabe, Yoshihisa
-
p. 1365 - 1370
(2007/10/02)
-