Diisopropylethylamine → N-(2-morpholinoethyl)-2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxamide

Participants

Reaction Steps

To a solution consisting of 2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxylic acid (Example 63, 172 mg, 0.61 mmol) in thionyl chloride (10 mL) was added one drop of dry DMF. The solution was heated at reflux for four hours and was subsequently allowed to reach room temperature and stirred for 18 hours. The thionyl chloride was evaporated away under reduced pressure and to the residue was added toluene (2×30 mL), which was evaporated and the residue subjected to high vacuum to remove residual thionyl chloride. The residue was dissolved in dichloromethane (10 mL) and 4-(2-aminoethyl)morpholine (51 mg, 0.051 mL, 0.40 mmol) was added followed by diisopropylethylamine (0.10 mL). The solution was stirred at room temperature for 18 hours. The solvent was removed under reduced pressure and the residue partitioned between water and diethyl ether. The organics were dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel flash chromatography (100% dichloromethane to 9:1 v/v dichloromethane-methanol gradient) through a 40-g Silicycle® flash silica cartridge. The title compound was obtained as an off-white solid (63 mg, 61% yield); Rf 0.70 with 9:1 v/v dichloromethane-methanol; 1H-NMR (300 MHz; CDCl3) δ 9.30 (s, 2H), 8.51 (m, 2H), 8.20 (s, 1H), 7.88 (br t, 1H), 7.53 (m, 3H), 3.77 (t, 4H); 3.61 (dt, 2H), 2.64 (t, 2H), 2.54 (t, 4H); MS (ESI+) m/z 396 (M+1); H-PGDS FPBA IC50: 2.5 μM.

Provenance & Evidence