Abstract: A practical and scalable synthesis of a key chiral piperidine intermediate of Niraparib was developed from commercially available 4-nitrophenylacetic acid. The eight-step route featured Nalkylation, amide coupling, cyclization, deprotection, borane-mediated lactam reduction, and L-(+)- tartaric acid resolution of the racemic amine 17, affording salt 9 in 99.85% ee. Subsequent protection and nitro reduction preserved stereochemical integrity, furnishing the desired intermediate in 99.80% ee and 99.91% HPLC purity, with an overall yield of 10.8% after and 12.9% before recrystallization. The process avoids the use of SFC and precious-metal catalysts, offering a practical route to this pharmaceutically important intermediate. results: Our synthesis starts with the commercially available nitrophenylacetic acid (15), which is coupled with chloroamine intermediate (14) to obtain the product (11). Initially, the reaction was conducted by using various activating agents [17-19] including CDI, EDC, and HATU. However, the coupling of (14), with (15) in the presence of CDI, in dichloromethane at room temperature was found to be the most effective and obtained the required key intermediate (11) in 93% yield which was purified by trituration with petroleum ether as a solid product. Subsequently, the compound (11) was than subjected for intramolecular nucleophilic substitution reaction to obtain the desired cyclized product with pyridine core (10) under various reaction conditions such as base, solvent, and temperature as shown in Table 1.
An extremely efficient, novel, and green protocol for the synthesis of biphenyl derivatives has been developed by using a highly efficient catalytic amount of Pd(OAc)(2) in aqueous extract of waste mango peels ash (MPE), a green, extremely cost-effective, operationally convenient, and environmentally benign medium under ambient temperature in the presence of air at very short reaction times (10-20 min) in ligand-, external base-, promoter-, and organic toxic solvent-free reaction environments. An in situ catalytic system was generated from the aqueous extract and Pd(OAc)(2), eliminating the need for any external base or ligand. Objectives: 1. Preparation of novel natural feedstock extracts and their applications in organic transformations. 2. A green and sustainable way for biaryl synthesis with respective yields. 3. To study the catalytic reusability in the Suzuki-Miyaura Cross-Coupling reaction.
A facile, environmentally friendly one-pot multicomponent protocol for the synthesis of dihydropyrimidinone (DHPM) and dihydropyrimidin(thio)one (DHPMT) derivatives has been developed using alumina-silica-supported MnO 2 as a catalyst in ethanol, demonstrating a green chemistry approach. The Biginelli-type reaction between aryl aldehyde, ethyl acetoacetate, and urea/thiourea afforded DHPM/DHPMT in 85-92% yield within 45 min. Essential features of this protocol include a short reaction time, the use of a heterogeneous catalyst, and convenient catalyst separation.
A group of 2-(4-aryl)-3-(cyclohexylimino)-2-hydroxy-2,3-dihydro-1 H -imidazo[1,2- a ]pyridin-4-ium chlorides was successfully synthesized in moderate yields through the reaction of Nef-Adducts (alpha-keto imidoyl chlorides), which were generated from the interaction of N -cyclohexyl isocyanide with aryl carbonyl chlorides, followed by the incorporation of 2-aminopyridine. The imidazo[1,2- a ]pyridin-4-ium chlorides produced were thoroughly characterized in this study, and the X-ray crystal structures of their salts were determined. This research examines the antimicrobial properties of the prepared compounds against various microbial strains. The findings suggest that compounds 7b and 7d exhibit the broadest and most potent activity.
Pyridyl-substituted imidazoles are privileged scaffolds in medicinal chemistry and homogeneous catalysis, yet their efficient and modular synthesis has long been a persistent challenge. The established synthetic methods mainly rely on precious metal catalysts, harsh reaction conditions, or multi-step operations, and are largely limited to aryl/alkyl-substituted imidazoles. Mild and efficient methods for the construction of multi-pyridyl-substituted imidazole frameworks remain exceptionally rare. Herein, we report a straightforward manganese-catalyzed one-step cyclization reaction that enables the direct synthesis of 2,4,5-trisubstituted pyridylimidazole derivatives from readily available pyridine-2-carboxaldehyde derivatives and ammonium acetate. This protocol features mild reaction conditions, no requirement for precious metals or strong bases, a broad substrate scope, excellent functional group tolerance, and good to excellent isolated yields (70-95%). This work provides a general and practical synthetic access to multi-pyridyl-substituted imidazoles, which will facilitate their widespread applications in drug discovery and transition-metal catalysis.
