Sodium Carbonate → HCID 59508402, compound

Participants

Reaction Conditions

Reaction Steps

Bis(triphenylphosphine)palladium(II) chloride (0.176 g, 0.25 mmol) was added to 3-[2-[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]propan-2-ylsulfonyl]propoxy-tri(propan-2-yl)silane (2 g, 3.74 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.107 g, 5.05 mmol) and 2M sodium carbonate solution (3 mL, 6.00 mmol) in a solvent mixture of DMF (5 mL), DME (8 mL), water (2 mL) and ethanol (1.5 mL) and the resulting mixture stirred at 90° C. for 5 hours, under an inert atmosphere. The reaction mixture was diluted with ethyl acetate (200 mL), and washed with water (2×100 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford a residue which was dissolved in DCM (100 mL), and tetrabutylammonium fluoride (18.72 mL, 18.72 mmol) added. The mixture was stirred at RT for 2 hours. The reaction mixture was diluted with DCM (100 mL), and washed sequentially with a saturated aqueous solution of ammonium chloride (50 mL) and water (2×100 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20 to 100% ethyl acetate in isohexane then 4% methanol in ethyl acetate, to give a material which was further purified by ion exchange chromatography using an SCX column, eluting with 7N ammonia in methanol, to give the desired material as a beige solid (1.0 g).

Provenance & Evidence