Acetaminophen Prodrug: Microwave-Assisted Synthesis andin vitroMetabolism Evaluation by Mass Spectrometry

Abstract

Propacetamol is an acetaminophen prodrug of intravenous administration used to control fever and pain of perioperative period in multimodal analgesia therapy. After injection, it is completely converted by plasma esterases into N,N-diethylglycine and acetaminophen, its active metabolite whose mechanism of action is the inhibition of prostaglandin synthesis. Herein, we report an improved protocol for the synthesis of propacetamol hydrochloride that allows the isolation of the active pharmaceutical ingredient (API) with high purity and yield. In addition, the in vitro metabolism of propacetamol in a microssomal reaction was evaluated by ion trap tandem mass spectrometry.

Synthesis of Covalent Conjugates of Dichloroacetic Acid with Polyfunctional Compounds

“…The most versatile was the reaction in the presence of DMAP at room temperature in chloroform or DMF (Table 1, method A, Schemes 1, 2). The paracetamol containing an acetamide group was used to show that the reaction in the presence of donor substituents required milder conditions and additional cooling as well as for monochloroacetyl chloride (method B) [9]. In the case of salicylic acid (containing an acceptor group), the best yields were achieved, but it requires the heating of the reaction mixture (method C).…”

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

“…Finally, to illustrate the importance and scope of the methodology, we used the commercially available 4-chloroquinazoline ( 16) and 4-chloro-2-methylquinazoline (17), which was pre-Scheme 5: N-Arylation reactions using 4-chloroquinazoline ( 16) and 4-chloro-2-methylquinazoline (17) to achieve the desired 4-anilinoquinazolines (4,(18)(19)(20).…”

“…On the other hand, long reaction times and low yields may be observed when electron-poor amines are applied in these reactions [17,18]. These limitations can be overcome by using microwave irradiation [12,13,[18][19][20], which promotes fast and efficient anilination reactions when a wide range of anilines bearing both electron-donating and electron-withdrawing groups are employed as nucleophiles (Scheme 1b) [12,13]. Moreover, 4-anilinoquinazolines can be prepared from N-methylanilines under basic [14] or acidic [15,16] (Scheme 1c) conditions.…”

Base-Controlled Regioselective Functionalization of Chloro-Substituted Quinolines

“…However, direct adaptation of these conditions to aminate 3,4,7-trichloroquinoline led to a pyrrolidine derivative as the major product. Over the last years, microwave (MW) irradiation has been used as a valuable tool to improve processes . We achieved 3-chloro chloroquine ( 15 ) in 65% yield when we performed the reaction in a MW reactor using glycerin as green polar solvent (Scheme ).…”