Reaction Steps
To a suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (1.45 g, 4.5 mmol) in CH3CN (25 ml), were added triethyl amine (1.56 mL, 11.22 mmol) and 4-methyl-2-phenyl-1,3-thiazole-5-carbonyl-chloride (1.07 g, 4.5 mmol). The mixture was stirred at room temperature overnight. The resulting suspension was filtered, and the solid was rinsed with CH3CN (20 mL), water (2×20 mL) and EtOAc (20 mL) to afford 4-methyl-2-phenyl-thiazole-5-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide as a white solid (1.45 g, 66%): mp, 277-279° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, gradient from 10/90 (CH3CN/H2O) to 95/5(CH3CN/H2O) in 10 minutes: tR=6.96 min. (99%); 1H NMR (DMSO-d6): δ 2.08-2.10 (m, 1H), 2.55-2.59 (m, 2H), 2.66 (s, 3H), 2.86-2.98 (m, 1H), 4.91 (d, J=5.6 Hz, 2H), 5.18 (dd, J=6, 12 Hz, 1H), 7.53-7.98 (m, 8H), 8.91 (t, J=5.6 Hz, 1H), 11.16 (s, 1H). 13C NMR (DMSO-d6) δ: 17.20, 30.92, 38.56, 48.87, 121.98, 125.65, 126.65, 126.25, 127.18, 129.37, 130.95, 131.57, 132.36, 133.15, 134.85, 138.83, 155.65, 161.37, 166.14, 166.93, 167.51, 169.82, 172.75. Anal Calcd for C25H20N4O5S: C, 61.47; H, 4.13; N, 11.47; S: 6.56. Found: C, 61.44; H, 4.04; N, 11.63; S: 6.49.
