Triphenylphosphine → ABT-072

Participants

Reaction Conditions

Reaction Steps

To a flask was added allylpalladium(II) chloride (0.98 g; 2.67 mmol) and triphenyl phosphine (2.8 g; 10.69 mmol). Vacuum and nitrogen purged. Sparged dimethylacetamide (50 ml) (nitrogen bubbled) was added and the solution was mixed at room temperature for 2 hrs. N-(4-((3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2 H)-yl)-2-methoxyphenyl)ethynyl)phenyl)methanesulfonamide (6) (50 g; 107 mmol) was dissolved in 100 mL of nitrogen sparged dimethylacetamide in a separate flask. This was inerted with nitrogen after the dissolution. The catalyst solution was transferred to the second flask containing substrate (6). Water (5 ml) and 1,1,1,2,2,2-hexamethyldisilane (16.1 mL; 160 mmol) were then added to the reaction mixture. The mixture was heated to 81° C. for total of 18 hours. The reaction mixture was cooled to ambient temperature and quenched with 500 ml THF and 500 ml of a solution of 7% NaCl, 2.5% NaHCO3 and 1% of cysteine. The quenched mixture was stirred for 1 hour and filtered to remove particulates. The filtrate was separated. The aqueous layer was back extracted with 250 mL THF and the combined organic layers washed again with 250 ml of a solution of solution of 7% NaCl, 2.5% NaHCO3 and 1% of cysteine. The organics were treated with activated carbon and the filtrate concentrated and solvent switched to 500 ml of methanol. The slurry was mixed at 50° C. for 60 minutes, cooled to ambient overnight. The slurry was filtered, and the solids washed with methanol, and dried to give 43.86 grams of 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