Ammonia → US9000184, 5, isomer 1

Participants

Reaction Conditions

Reaction Steps

(7′-Bromo-4-methoxy-5″-methyl-3′,4′-dihydrodispiro[cyclohexane-1,2′-naphthalene-1′,2″-imidazole]-4″(3″H)-thione (Intermediate 15, 0.191 g, 0.47 mmol) and ammonia (7M in MeOH, 2.5 mL, 17.5 mmol) were mixed in a microwave vial. The vial was sealed and the reaction was heated at 120° C. for 30 min in a microwave reactor. The mixture was concentrated and the residue was dissolved in ammonia (7M in MeOH, 2.5 mL, 17.5 mmol) and heated at 120° C. for 30 min in a microwave reactor. This was repeated six more times (8 runs in total). After evaporation of the solvent, the residue was partitioned between DCM and 2 M citric acid. The phases were separated and the organic layer was extracted with 2 M citric acid. The organic layer was discarded while the combined aqueous phases were basified to ˜pH 12 by addition of 50% aq. NaOH. The aqueous phase was then extracted with EtOAc three times. The combined organic layers were dried using a phase separator and concentrated. The product was purified by preparative HPLC to give two isomers:

Provenance & Evidence