External cooling was applied throughout the process to keep the temperature below 108 °C and the stirring was continued for 30 minutes after all of the bromine had been added. The precipitate of imino-benzothiazole hydrobromide

was removed by filtration with a pump, dissolved in warm water, and the base was BTK inhibitor price precipitated with alkali. The residue was recrystallized from alcohol or ligroin to yield the derivatives of 2-amino-4-(5-or 6-) substituted benzothiazole (3a–h). To a mixture of phenylacetic acid/4-methoxyphenylacetic acid (0.0073 mol), anisole (0.0088 mol) and 88–93% orthophosphoric acid (0.0088 mol) was added trifluoroacetic anhydride (0.0295) rapidly with vigorous stirring at 25 °C. The mixture turned into a dark colored solution and a vigorous exothermic reaction was observed. The mixture was stirred for 30 min at the same temperature and poured into ice-cold learn more water (50 mL) with stirring, the products appeared as solid and the filtered solid, after washing with cold hexane (2 × 10 mL), was often analytically pure (6a–i). To a solution of (6a–i) (0.2 mol) in chloroform (30 ml) kept at 50 °C was added dropwise bromine (0.22 mol) with stirring. After being stirred at 50 °C for 0.5 h, the mixture was washed successively with aqueous 10% sodium thiosulphate solution and water. The solvent

was removed in vacuo to obtain the compounds (7a–i) either as sold mass/oil crystalline/liquid compounds. A mixture of 2-amino substituted benzothiazole (3a–h) (10 mmol) and an appropriate α-bromo-1-[4′-substituted] phenyl-2-[4″-(un)substituted] phenyl-1-ethanone (7a–i) (10 mmol) in dry ethanol (50 mL) was heated to reflux on a water bath for 6–8 h, phosphorus pentoxide (3 m mol) was added, and refluxing was continued for another 4–6 h. The reaction mixture was cooled DNA ligase overnight at room temperature. Excess of solvent was removed under reduced pressure and the solid hydrobromide separated was filtered, washed with cold ethanol, and dried. Neutralization of hydrobromide salts with cold aqueous solution of Na2CO3 yielded the corresponding free bases (8a–y), which were purified by recrystallization from dry ethanol. This

compound was prepared as per the above mentioned procedure purified and isolated as yellow solid: yield 49.0% mp 208 °C; IR (KBr) vmax 2950, 2834, 1714, 1280, 761 cm−1; 1H NMR (CDCl3) δ ppm; 11 (s, 1H, COOH), 7.34–7.89 (m, 11H, Ar–H), 2.62 (s, 3H, CH3); 13C NMR (CDCl3) δ ppm; 168.3, 157.7, 144.8, 139.7, 137.7, 134.8, 134.3, 133.4, 131.4, 130.6, 130.1, 130.4, 129.7, 129.3, 128.4, 126.6, 125.6, 124.3, 122.4, 22.4; HRMS (EI) m/z calcd for C23H15ClN2O2S: 418.0543; found: 418.0150. This compound was prepared as per the above mentioned procedure purified and isolated as dark yellow solid: yield 78.29% mp 201 °C; IR (KBr) vmax 2950, 2812, 1716, 1320, 745 cm−1; 1H NMR (CDCl3) δ ppm; 11 (s, 1H, COOH), 7.20–7.70 (m, 11H, Ar–H), 3.79 (s, 3H, OCH3); 13C NMR (CDCl3) δ ppm; 168.3, 162.4, 157.3, 144.2, 139.