Azetidine → HCID 178508467, compound

Participants

Reaction Conditions

Reaction Steps

General procedure to Examples 33 and 34: A THF solution (3 mL) of trans-toluene-4-sulfonic acid 4-[8-amino-1-(3-benzyloxy-phenyl)imidazo[1,5-a]pyrazin-3-yl]-cyclohexylmethyl ester (200 mg, 0.34 mmol) in a sealed tube was charged with azetidine (8.92 mmol, 510 mg) and stirred at 50° C. for 24 h. The reaction mixture concentrated in vacuo and partitioned b/w EtOAc and sat. NaHCO3. The organic layer was washed with sat. NaHCO3 (2×), water (1×), brine (1×), dried over Na2SO4, filtered, and concentrated to a yellow oil. The crude material was purified by silica gel column chromatography [Jones Flashmaster, 5 g/25 mL cartridge, eluting with CH2Cl2 to 2% ˜7 N NH3 in MeOH/CH2Cl2] to afford trans-3-(4-azetidin-1-ylmethyl-cyclohexyl)-1-(3-benzyloxy-phenyl)-imidazo[1,5-a]pyrazin-8-ylamine as a white solid (130 mg, 82%).

Provenance & Evidence