Moreover, quinolin-4(1H)-Imines are gaining prominence in clinical research and development (Figure ). It is generally accepted that the introduction of the difluoromethylene group into organic molecules can lead to impressive increases in the pharmacodynamic activity of drug candidates. Consequently, every year, a large number of diversified fluoro-pharmaceuticals often appear in the marketed drugs. Given the vital importance of these advantages, the incorporation of the CF2H motif into such Nheterocycles represents a highly attractive approach, as these site-specific fluorinated compounds serve as medicinally relevant scaffolds to quickly diversify molecular fragments. In addition, quinolone derivatives are highly attractive in core pharmaceuticals such as Ivacaftor, Nalidixic acid, Ciprofloxacin, and many more (these drugs contain N-H/R) (Figure ); the replacement of the CF2H group with an N-alkyl fragment or N-H bond in such drugs would play an essential role in drug repositioning. However, efforts to prepare the aforementioned structurally complex variants of the pharmaceutically privileged Het-NCF2H compounds featuring either imine or ketone functional groups remain an underdeveloped goal in organofluorine chemistry, presumably due to the lack of synthetic methodologies.