Pyridine → tert-Butyl 1-(4-(6-(4-chlorophenyl)-4-oxothieno[3,2-d]pyrimidin-3(4H)-yl)-2-methoxyphenoxy)-2-methylpropan-2-yl oxalate

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Reaction Steps

To oxalyl chloride (0.50 mL; 5.91 mmol) cooled to 0° C. was added t-butanol (0.28 mL; 2.95 mmol) over 30 min. After warming the solution to rt and concentration under reduced pressure, the residue was dissolved in 1 mL of CH2Cl2 whereupon 6-(4-chlorophenyl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)thieno[3,2-d]-pyrimidin-4(3H)-one (100 mg; 0.219 mmol) (the product of Example 82) and pyridine (42 uL; 0.522 mmol) were added. After the suspension was stirred at rt for 1.5 h, the solution was diluted with CH2Cl2, washed with 1N HCl 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 1:1 gradient) to afford 120 mg (94%) of the title compound as a white foam. 1H NMR (CDCl3) δ 1.55 (s, 9H), 1.70 (s, 6H), 3.87 (s, 3H), 4.24 (s, 2H), 6.92 (dd, J=8.25 Hz, 2.20 Hz, 1H), 6.96 (d, J=2.20 Hz, 1H), 7.04 (d, J=8.24 Hz, 1H), 7.44 (d, J=8.79 Hz, 2H), 7.53 (s, 1H), 7.65 (d, J=8.79 Hz, 2H), 8.13 (s, 1H); 13C NMR (CDCl3) δ 23.14, 27.74, 56.36, 74.39, 84.26, 84.51, 111.76, 115.30, 119.27, 120.84, 123.22, 127.65, 129.47, 130.78, 131.54, 135.67, 148.19, 149.25, 150.64, 151.63, 156.77, 157.22, 157.35, 157.60; HPLC (Method #1) 4.40 min retention time, (100%); MS (ES): m/z 585 [M+H]+.

Provenance & Evidence