Pyridine → (S,S)-2-[4-(2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-yl)-piperazin-2-yl)-1-phenyl-ethanol

Participants

Reaction Conditions

Reaction Steps

Add methyl trifluoromethanesulfonate (174 μL, 1.53 mmol) to a 0° C. slurry of 2-methyl-4,9-dihydro-3-thia-4,9-diaza-benzo[f]azulene-10-thione (315 mg, 1.28 mmol) in dichloromethane (4 mL). Stir 1 h at 0° C. then warm to ambient temperature and stir 18 h. Concentrate the reaction to an orange powder. Add (S)-1-phenyl-2-piperazin-2-yl-ethanol (264 mg, 1.28 mmol) and pyridine (5 mL). Heat to 110° C. for 5.5 h and stir at ambient temperature for 18 h. Concentrate the reaction, dissolve the residue in methanol-dichloromethane, apply to a SCX column. Wash the column with methanol-dichloromethane to remove impurities then elute the product with 2N ammonia in methanol-dichloromethane (10%). Concentrate and purify by radial silica gel chromatography using a 2 mm plate and 2N ammonia in methanol-methylene chloride (2.5%–3%) as the eluent to give 39 mg of (S,R)-2-[4-(2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-1-phenyl-ethanol and 130 mg of (S,S)-2-[4-(2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-yl)-piperazin-2-yl]-1-phenyl-ethanol.

Provenance & Evidence