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Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Practical, asymmetric route to sitagliptin and derivatives: development and origin of diastereoselectivity
Osvaldo Gutierrez1, Dattatray Metil, Namrata Dwivedi
1‡Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 United States.
Abstract:
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.
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