Potassium Phosphate, Tribasic → HCID 68157919, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of the 2-bromo-3-methoxy-5-(tetrahydro-pyran-4-ylmethyl)-cyclopent-2-enone (150 mg, 0.5 mmol), 1,5-dimethyl-1H-indazole-4-boronic acid (148 mg, 0.78 mmol) and freshly powdered potassium phosphate tribasic (221 mg, 1 mmol) in anhydrous, de-gassed toluene (1.5 ml) under a nitrogen atmosphere were added palladium acetate (6 mg, 0.03 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (21 mg, 0.05 mmol). The reaction was heated to 140° C. for 30 minutes in the microwave (using “normal” absorbtion). The reaction was diluted with water (10 ml) and extracted with ethyl acetate (3×15 ml). The combined organic extracts were washed with brine (10 ml), dried over magnesium sulfate and evaporated to dryness under reduced pressure to give a brown oil. The crude product was purified by column chromatography (30% EtOAc/hexane to 100% EtOAc as eluent) to give 2-(1,5-Dimethyl-1H-indazol-4-yl)-3-methoxy-5-(tetrahydro-pyran-4-ylmethyl)-cyclopent-2-enone (41 mg). This material was dissolved in acetone (2 ml) and 2 M hydrochloric acid (2 ml) added. This solution was heated in the microwave (using “normal” absorbtion) for 1 h at 120° C. This solution was then extracted with dichloromethane (2×10 ml) and the organics dried over magnesium sulfate and reduced in vacuo. The crude material was purified by reverse phase preparative HPLC (eluting with acetonitrile/water) to give 2-(1,5-dimethyl-1H-indazol-4-yl)-4-(tetrahydro-pyran-4-ylmethyl)-cyclopentane-1,3-dione (4 mg).

Provenance & Evidence