Process for preparing saxagliptin and its novel intermediates useful in the synthesis thereof
Methods of making saxagliptin, pharmaceutically acceptable salts and hydrates thereof and intermediates thereof.
1. A method for making saxagliptin hydrochloride monohydrate comprising:
combining (S)-(+)-p-toluenesulfinamide Ti(OEt) 4 and adamantane 1-carboxaldehyde to obtain
wherein R is alkyl or aryl,
treating the resulting compound with NaCN, KCN, trimethylsilyl cyanide (TMSCN) or Et 2 AlCN and (S)-(+)-p-toluenesulfonamide/Ti(OEt) 4 to obtain
treating the resulting compound with phthalic anhydride to obtain
treating the resulting compound with acid to obtain
treating the resulting compound with KMnO 4 to obtain
coupling the resulting compound with methanoproline nitrile using hydroxybenzotriazole (HOBT), 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC HCl) or N,N-diisopropylethylamine (DIPEA) to obtain
treating the resulting compound with methyl amine and hydrochloric acid.