An Improved Manufacturing Process for the Antimalaria Drug Coartem. Part II

Abstract

The manufacturing process for lumefantrine, 2, one of the two active principles in the fixed-dose combination of the antimalarial drug Coartem, was reworked. For the conversion of 2-chloro-1-(2,7-dichloro-9H-fluoren-4-yl)ethanone, 5, to 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl)ethanol, 8, a onepot process was developed that eliminated isolation of the epoxide 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane, 7. Significant increase in throughput was achieved by applying new reaction and crystallization conditions for the Knoevenagel condensation of 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl)ethanol, 8, to 2-dibutylamino-1-{2,7-dichloro-9-[1-(4-chlorophenyl)meth-(Z)ylidene]-9H-fluoren-4-yl}ethanol, 2.

Silica Bonded N-(Propylcarbamoyl)sulfamic acid (SBPCSA) Mediated Expeditious Approach to C–C Bond Formation: An Innovative Pathway for Acrylonitrile Derivatives

“…The Knoevenagel condensation between aldehydes and ketones with activated methylene compounds is one of the reactions which facilitates C-C bond formation [19,20] and has been exploited in the synthesis of some vital drugs such as entacapone [21] pioglitazone [22] and lumefantrine [23]. The use of ammonia, amines, pyridine, piperidine and their salts as basic catalysts in Knoevenagel condensation restricts their applications due to their hazardous environmental concerns, carcinogenic nature, problem in product separation and reusability [24].…”

Crystal structure of (E)-2-(benzo[d]thiazol-2-yl)-3-(pyridin-3-yl)acrylonitrile)

“…In addition, this family of compounds have been proved for having prominent biological properties as antifungal, antitumor, and antibacterial activities [3][4][5][6][7], as well as applications for the design of dendrimers [8] and uorescent probes for visualizing endogenous thiols in living cells [9,10]. They have also been reported in the literature as versatile building-blocks for molecules with potential biological or pharmaceutical applications [11][12][13][14][15][16][17].…”

Some Progress in Organic Synthesis of Pharmaceuticals in China

“…This new fixed-dose presents the merits of the two components while avoiding their individual limitations. Meanwhile, the recrudescence to drug was largely lowered [52]. Coartem facilitates compliance and supports optimal clinical efficiency.…”