Efficient synthesis of deuterium labeled hydroxyzine and aripiprazole

Hydroxyzine and aripiprazole are active pharmaceutical ingredients that have been largely acknowledged for their antipsychotic properties. Deuterium labeled isotopes of hydroxyzine and aripiprazole are internal standards that can aid in the further research of non‐isotopic forms via quantification analysis using HPLC‐MS/MS. The synthesis of hydroxyzine‐d8 was accomplished by coupling piperazine‐d8 with 4‐chlorobenzhydryl chloride followed by the reaction of the first intermediate with 2‐(2‐chloroethoxy) ethanol to afford 11.7% of hydroxyzine‐d8 with 99.5% purity. The synthesis of aripiprazole‐d8 was also achieved in two steps. 1,4‐Dibromobutane‐d8 reacted with 7‐hydroxy‐3,4‐dihydro‐2(1H)‐quinolinone. The first intermediate was then coupled with 1‐(2, 3‐dichlorophenyl)piperazine hydrochloride to produce 33.4% of aripiprazole‐d8 with 99.93% purity. Hydroxyzine‐d8 and ariprazole‐d8 were successfully prepared and can be used as internal standards for bioanalytical purposes. An efficient synthetic method involving two convenient steps was developed for both molecules by performing brief optimization studies. Our approach resulted in a yield of 11.7% and 33.4% for hydroxyzine‐d8 and aripiprazole‐d8, respectively.
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: Research Article Source Type: research