Cesium carbonate → HCID 52935514, compound

Participants

Reaction Conditions

Reaction Steps

To (5S*,6S*)-6-(aminomethyl)-1-azabicyclo[3.2.1]octan-6-ol dihydrochloride (84 mg, 0.54 mmol) in DMF (3 mL) was added 3-isothiocyanatoisoquinoline (100 mg, 0.54 mmol) and cesium carbonate (526 mg, 1.61 mmol). The reaction was heated to 80° C. for 2 hours and then treated with 1,3-diisopropylcarbodiimide (0.168 mL, 1.08 mmol). The reaction was maintained at 80° C. for 18 hours and then cooled to room temperature. The crude reaction was purified by silica gel chromatography, eluting with 5-40% (10% NH4OH/methanol) in chloroform. The desired product was collected and concentrated to give (5S*,5′R*)—N-(isoquinolin-3-yl)-4′H-1-azaspiro[bicyclo[3.2.1]octane-6,5′-oxazol]-2′-amine as a yellow solid (34 mg, 20% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.15 (br. s., 1H) 8.96 (s, 1H) 7.86 (d, J=8.03 Hz, 1H) 7.70 (d, J=8.28 Hz, 1H) 7.55 (t, J=7.28 Hz, 1H) 7.31-7.42 (m, 2H) 4.10 (d, J=9.03 Hz, 1H) 3.96 (d, J=9.03 Hz, 1H) 3.60 (d, J=14.05 Hz, 1H) 3.31 (d, J=11.80 Hz, 1H) 3.09 (dd, J=14.05, 2.01 Hz, 1H) 2.81-3.01 (m, 3H) 2.30 (d, J=3.01 Hz, 1H) 1.74-1.91 (m, 2H) 1.42-1.58 (m, 2H). MS: (LC/MS) RT=0.797 mins [M+H]=309.01.

Provenance & Evidence