HCID 22251100, compound → HCID 22251152, compound

Participants

Reaction Steps

To a solution of 2-chloro-N-cyclohexyl-N-phenylacetamide (503 mg, 2.0 mmol) in acetone (30 mL) was added sodium iodide (800 mg, 5.6 mmol). The reaction mixture was heated at reflux for 4 hours before it was cooled to room temperature. The solid material was filtered off, and the solvent removed from the filtrate under reduced pressure, to afford 2-iodo-N-cyclohexyl-N-phenylacetamide, which was subjected to subsequent reactions without further purification. B. To a solution of 2-iodo-N-cyclohexyl-N-phenylacetamide (obtained from A. above) in anhydrous DMF (30 mL) was added sodium azide (325 mg, 5.0 mmol), and the contents were heated at 80° C. for 10 hours. The reaction mixture was filtered, the solids washed with acetone (2×5 mL), and the solvent removed from the filtrate under reduced pressure, to afford 2-azido-N-cyclohexyl-N-phenylacetamide. C. To a solution of 2-azido-N-cyclohexyl-N-phenylacetamide (obtained from B. above) dissolved in methanol (50 mL) was added 10% Pd/C (90 mg, 0.09 mmol), and the reaction suspension was hydrogenated at room temperature under hydrogen (50 psi) for 5 hours. After filtration and concentration, the crude product was purified on silica gel using a methanol/dichloromethane gradient (0% to 10% methanol) to furnish 2-amino-N-cyclohexyl-N-phenylacetamide (320 mg, 69% yield). D. To a solution of exo-2-chloro-syn-7-hydroxymethyl-5-oxo-bicyclo[2.2.1]heptane (35 mg, 0.20 mmol) in 1-butanol (6 mL) was added 2-amino-N-cyclohexyl-N-phenylacetamide (46 mg, 0.20 mmol) and triethylamine (50 μL, 0.36 mmol). The reaction mixture was stirred at 100° C. for 2 days, then cooled to room temperature, concentrated under reduced pressure, and the residue purified on silica gel (10% methanol/dichloromethane) to afford N-cyclohexyl-2-{[7-(hydroxymethyl)-5-oxobicyclo[2.2.1]hept-2-yl]amino}-N-phenylacetamide CVT-6440 (8 mg, 10% yield). (M+1)=371.15. B. Preparation of a Compound of Formula I in which X is —N— and Z is —C(O)—

Provenance & Evidence