Hydrogen Peroxide → dibenzyl 1-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl phosphate

Participants

Reaction Steps

A suspension of 6-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]pyrimidin-4(3H)-one (Example 82) (3.00 g; 6.56 mmol), 1,2,4-triazole (1.36 g; 19.7 mmol) and dibenzyl N,N-diisopropylphosphoramidite (6.62 mL; 19.7 mmol) in 40 mL of CH2Cl2 was heated at reflux for 16 h. The solution was cooled to rt, 30% H2O2 in water (4.00 mL; 35.3 mmol) was added and the solution stirred at rt for 2.5 h. The solution was diluted with CH2Cl2, washed with 1M sodium metabisulfite, 1N HCl, water and brine, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, Hexanes/EtOAc; 100:0 to 0:100 gradient) to afford 3.79 g (80%) of the title compound as a white solid. 1H NMR (CDCl3) δ 1.65 (s, 6H), 3.75 (s, 3H), 4.07 (s, 2H), 5.04-5.06 (m, 4H), 6.87-6.96 (m, 3H), 7.29-7.35 (m, 10H), 7.44 (d, J=8.24 Hz, 2H), 7.53 (s, 1H), 7.66 (d, J=8.25 Hz, 2H), 8.10 (s, 1H); 13C NMR (CDCl3) δ 22.56, 25.04, 56.08, 68.98, 69.03, 75.36, 82.87, 111.30, 113.91, 119.15, 120.87, 127.42, 127.67, 127.88, 128.33, 128.48, 129.47, 130.33, 131.54, 135.69, 136.07, 148.19, 149.10, 150.19, 151.63, 156.79, 157.37; HPLC (Method #1) 4.85 min retention time, (100%); MS (ES): m/z 717 [M+H]+.

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