1621689-64-2

Upstream product

• 2033-24-1 cycl-isopropylidene malonate 
• 451-82-1 (2-fluorophenyl)acetic acid 
• 451-81-0 2-(2-fluorophenyl)acetyl chloride 

Downstream Products

• 221121-35-3 ethyl 4-(2-fluorophenyl)-3-oxobutanoate 
• 1449301-78-3 ethyl 5-(2-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxylate 

Relevant academic research and scientific papers

Practical, asymmetric route to sitagliptin and derivatives: Development and origin of diastereoselectivity

The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S=O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.

Bioisosteric replacement of an acylureido moiety attached to an indolin-2-one scaffold with a malonamido or a 2/4-pyridinoylamido moiety produces a selectively potent Aurora-B inhibitor

Bioisosteric replacement of acylureido moiety in 6-acylureido-3- pyrrolylmethylidene-2-oxoindoline derivatives resulted in a series of malonamido derivatives with indolin-2-one scaffold (11-14). Further conformational restrictions of the malonamido moiety led to 2-oxo-1,2-dihydropyridine (21-25) or a 4-oxo-1,4-dihydropyridine derivatives (31-36). 4-Oxo-1,4-dihydropyridine derivatives were more potent Aurora B inhibitors than their 2-oxo-1,2- dihydropyridine counterparts and demonstrated cytotoxicities against A549 and HepG2 cells in the submicromolar range. In A549 cells, 31h decreased phosphorylation of histone H3, triggered polyploidy, induced expression of pro-apoptotic Fas and FasL with subsequent activation of caspase 8, resulting into apoptosis. In a Huh7-xenograft mouse model, 31h demonstrated potent in vivo efficacy with a daily dose of 5 mg/kg.