Benzyl N-[(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamate → Saxagliptin

Participants

Reaction Steps

To a solution of benzyl N-[(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo-ethyl]carbamate (10 gm) (formula-IX) in acetonitrile, 5% Pd/C (50% wet, 1 gm) was added. Hydrogen gas was bubbled through the reaction mass for 4 hrs at 20-25° C. After complete conversion of starting material, the reaction mass was filtered, the filtrate was evaporated to yield SAXAGLIPTIN free base of formula-I as a foamy solid. The solid was dissolved in ethyl acetate (50 ml) and concentrated hydrochloric acid (2.4 ml) was added at 5-10° C. The white solid formed was filtered to yield 7.8 gm (99%) of SAXAGLIPTIN dihydrate mono-hydrochloride M.P: 228-230° C., HPLC: 99.7% (A) and the content of the impurity cyclic amidine: 0.05% (A), H1NMR (300 MHz, Methanol-d4): 0.87-1.13 (m, 2H), 1.48-1.7 (m, 12H), 1.89-1.96 (ddd, 1H), 2.19 (s, 1H), 2.22-2.28 (dd, 1H), 2.49 (ddd, 1H), 3.83-3.88 (ddd, 1H), 4.19 (s, 1H), 5.08-5.12 (dd, 1H).

Provenance & Evidence