Water → ABT-072

Participants

Reaction Conditions

Reaction Steps

To a vessel N-(4-((3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)ethynyl)phenyl)methanesulfonamide (6) (5.00 g; 10.69 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.375 g; 5.35 mmol) are charged and the vessel is purged with nitrogen. Nitrogen purged dimethylacetamide (20 ml) and water (0.578 g, 32.1 mmol) are charged to the vessel and the mixture was heated to 70° C. Triethylsilane (2.49 g, 21.4 mmol) was charged over 2 hours at a temperature of 70° C. The mixture was heated at 70° C. for approximately 5 hours and cooled to ambient temperature. The mixture was diluted with tetrahydrofuran (40 g) and extracted with a 1% Cysteine/2.5% NaHCO3/7% NaCl solution. The solids which formed were removed by filtration and washed with tetrahydrofuran (18 g). The aqueous layer was extracted with tetrahydrofuran (18 g). The combined tetrahydrofuran extracts were washed successively with a 1% Cysteine/2.5% NaHCO3/7% NaCl solution and a 2.5% NaHCO3/7% NaCl solution. Methanol (28 g) was charged and the solution concentrated to 28 g. Methanol (28 g) was charged and the product was allowed to crystallize. Methanol (28 g) was charged and the slurry was concentrated to 45 g. Methanol (60 g) was charged and the mixture concentrated to 75 g. The slurry was heated to 60° C. for 30 minutes and then cooled to ambient temperature. The solids were isolated by filtration, washed with methanol (2×8 gm) and vacuum dried at 50° C. to provide 4.42 g 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/e 470.1 (M+H)+.

Provenance & Evidence