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The present work describes a two-step process, namely, silylation with (chloro­methyl)­dimethyl­chloro­silane and desilylation, to address the selectivity problem in the N-methylation of a pyrimidone intermediate toward the synthesis of the raltegravir active pharmaceutical ingredient. The said methodology delivers the desired drug substance in which the O-methylated impurity content is below the detection limit by high-performance liquid chromatography analysis. Moreover, this two-step, one-pot procedure provides an apparent advantage in terms of environmental impact with respect to the optimum approach described in the literature, while it compares equally well in terms of cost and operational simplicity.

A concise, scalable, and industrially applicable process for the synthesis of the antidepressant agomelatine is described. The process relies on a tandem allylic chlorination–isomerization sequence, on a tetralone‐derived allyl carbinol, as the key transformation. The target compound is obtained in five steps from commercially available 7‐methoxy‐1‐tetralone, in 52.3 % overall yield after final recrystallization.

An eco-friendly, high-yielding, and transition-metal-free synthesis of 2-[(2,4-dimethylphenyl)thio]aniline precursor to vortioxetine is reported. Vortioxetine, a multi-modal acting drug with high affinity for a range of serotonergic targets, is used for the treatment of major depressive disorder (MDD). The synthesis – applicable in multi-gram scale – involves the reaction of bis(2,4-dimethyl)iodonium bromide with commercial 2-aminophenyl disulfide, whereas its reaction with 2-aminothiophenol afforded the same product but in low to moderate yields. This method works equally well in deep eutectic solvents (DESs), based on choline chloride (ChCl).