Triphenylphosphine → ABT-072

Participants

Reaction Conditions

Reaction Steps

To a flask was successively added N-(4-((3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)ethynyl)phenyl)methanesulfonamide (6) (20 g; 42.60 mmol); allylpalladium(II) chloride (0.39 g; 1.06 mmol); triphenylphosphine (1.12 g; 4.26 mmol) and a solution of dimethylacetamide (80 ml)/water (2.3 ml) previously purge with nitrogen. The solution was heated at 70° C. for 30 minutes. To the reaction mixture was then added over 3 hours triethylsilane (7.42 g; 63.90 mmol). The mixture was stirred for 12 hours at 70° C. The reaction was cooled at 23° C. then diluted with tetrahydrofuran (180 ml) and successively washed with a solution of 1% Cysteine/2.5% NaHCO3/7% NaCl and a solution of 2.5% NaHCO3/7% NaCl. The organic layer was treated with activated carbon and the filtrate was concentrated down and solvent switched to methanol. The slurry was mixed at 62° C. for 60 minutes, cooled down to 25° C., mixed for 2 hours, filtered, and washed with methanol to give the titled compound. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.35 (s, 9 H) 2.99 (s, 3 H) 3.76 (s, 3 H) 5.62 (d, J=7.82 Hz, 1 H) 7.12-7.29 (m, 5 H) 7.51-7.65 (m, 3 H) 7.72 (d, J=7.82 Hz, 1 H) 9.83 (s, 1 H) 11.39 (s, 1 H) MS (APCI) m/z 470.1 (M+H)+.

Provenance & Evidence