Hydrochloric Acid → Ammonia methanol dichloromethane

Participants

Reaction Steps

Borane (2.00 ml of a 1.0M solution in tetrahydrofuran, 2.00 mmol) was added to a stirred solution of the pyrazole of Example 97 (326 mg, 1.00 mmol) in tetrahydrofuran (10 ml) at room temperature under nitrogen. The reaction was heated under reflux for 5 hours and further borane (3.00 ml of a 1.0M solution in tetrahydrofuran, 3.00 mmol) was added. The reaction was heated under reflux for 14 hours and further borane (2.00 ml of a 1.0M solution in tetrahydrofuran, 2.00 mmol) was added. The reaction was heated under reflux for 3 hours and further borane (2.00 ml of a 1.0M solution in tetrahydrofuran, 2.00 mmol) was added. The mixture was cooled to room temperature, 2M hydrochloric acid (10 ml) was added and the mixture was heated under reflux for 1 hour, The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in dichloromethane (40 ml), washed with 1M aqueous potassium carbonate solution (30 ml), dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol (98:2, by volume), then dichloromethane:methanol (95:5, by volume) and then dichloromethane:methanol:ammonia (90:9:1, by volume) to provide the title compound (219 mg) as a white solid, m.p. 76-77° C.

Provenance & Evidence