Reaction Steps
To a solution of 6-(4-chlorophenyl)-3-(3-ethyl-4-(2-hydroxy-2-methylpropoxy)-phenyl)thieno[3,2-d]pyrimidin-4(3H)-one (0.96 g, 2.11 mmol), 4-pyrrolidinopyridine (0.31 g, 2.11 mmol) and N-(tert-butoxycarbonyl)glycine (1.11 g, 6.33 mmol) in 20 mL of CH2Cl2 heated at reflux was added diisopropylcarbodiimide (0.98 mL; 6.33 mmol) over 3 h via syringe pump. The suspension was heated at reflux for 1 h and additional N-(tert-butoxycarbonyl)glycine (0.55 g, 3.17 mmol) was added followed by diisopropylcarbodiimide (0.55 mL, 3.17 mmol) over 2 hrs via syringe pump. The suspension heated at reflux for 1 h and cooled to rt. Hydrazine monohydrate (0.34 mL, 7.01 mmol) was added and the suspension stirred at rt for 2 h. The suspension was cooled to 0° C., filtered and the filtrate washed with cold, 1N HCl, cold, dilute NaHCO3 solution, dried over anhydrous MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAc/Hexanes, 0:100 to 1:1 gradient) to afford 1.37 g (100%) of the title compound as an off-white solid. 1H NMR (CDCl3) δ 1.24 (t, 3H), 1.45 (s, 9H), 1.64 (s, 6H), 2.68-2.73 (m, 2H), 3.85 (d, J=4.95 Hz, 2H), 4.18 (s, 2H), 4.98 (br s, 1H), 6.92 (d, J=9.35 Hz, 1H), 7.20-7.22 (m, 2H), 7.44 (d, J=8.79 Hz, 2H), 7.53 (s, 1H), 7.66 (d, J=8.25 Hz, 2H), 8.13 (s, 1H); 13C NMR (CDCl3) δ 13.68, 23.39, 23.67, 28.28, 42.87, 72.72, 79.86, 81.86, 111.48, 120.82, 123.25, 125.42, 127.62, 129.42, 129.67, 131.54, 134.25, 135.59, 148.29, 151.50, 155.58, 156.69, 156.92, 157.37, 169.47; HPLC (Method #1) 4.80 min retention time; LCMS (ES): m/z 612 [M+H]+.
