An improved synthesis of etravirine

Etravirine (1) is a novel diarylpyrimidine non-nucleoside reverse transcriptase inhibitor and has recently been approved by the U.S. Federal Drug Administsration for the treatment of AIDS. Its reported synthesis is fraught with many difficulties, the foremost being the poor yield and long reaction time required at the aminolysis stage. We attributed this problem to the presence of a bromide group adjacent to the reaction site of the advance intermediate (6). In order to circumvent this issue, we proposed to defer the installation of the bromide group at a later stage, preferably after aminolysis. Indeed, this protocol has worked well. However, in the process of installation of diarylether and diarylamine functionalities at appropriate positions, we had to reverse the sequence of displacement reactions of the dichloride intermediate (9) with 3,5-dimethyl-4-hydroxybenzonitrile (5) and 4-aminobenzonitrile (3). The classical bromination led to the completion of etravirine synthesis

A rare case of Crigler–Najjar syndrome type 2: A case report and literature review

Key Clinical Message Crigler–Najjar syndrome type 2 should be suspected in any young patient presenting with isolated indirect hyperbilirubinemia where all other common etiologies have been excluded. It is a relatively benign condition that responds to phenobarbitone. Abstract Crigler–Najjar syndrome (CNS) type 2 is an inborn cause of isolated indirect hyperbilirubinemia characterized by a partial deficiency of the enzyme uridine 5′‐diphosphate‐glucuronosyltransferase (UGT) responsible for bilirubin conjugation. Typically, this condition is diagnosed based on clinical manifestations, supplemented by enzyme analysis if feasible, and exhibits a significant response to phenobarbitone, known for its enzyme‐inducing properties. In this case, we present a young male patient who had experienced recurrent isolated indirect hyperbilirubinemia since early childhood, with negative results in the hemolytic workup. The patient exhibited a UGT1A1 gene defect and demonstrated a highly favorable response to phenobarbitone treatment. The purpose of this report is to raise awareness among physicians about this benign condition and underscore the importance of avoiding unnecessary investigations