for C28H24F2N7O3S [M + H]+ 576
for C28H24F2N7O3S [M + H]+ 576.1624, found 576.1637. (16d) Based on the procedures explained for the synthesis of 15a, compound 16d were obtained as a white sound (51 mg) in 58% yield, m.p. yield, m.p. 185C186 C; 1H-NMR (DMSO-d6) 9.44 (s, 1H, SO2NH), 7.21 (td, = 9.0, 3.0 Hz, 1H, Ar-H), 7.07 (td, = 8.4, 1.5 Hz, 1H, Ar-H), 7.01 (d, = 7.8 Hz, 2H, Ar-H), 6.97 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 6.85 (dd, = 9.0, 4.8 Hz, 1H, Ar-H), 5.85 (s, 2H, NH2), 2.04 (s, 6H, 2,6-(CH3)2); MS (ESI) calcd. for C14H14FN2O2S [M ? H]?: 293.1, found: 293.3. (9) A mixture of 7 (5 g, 18.1 mmol), trimethyl orthoacetate (50 mL) and 4? molecular sieve (10 g) was refluxed for 10 h. After cooling to room temp., the combination was concentrated and the residue was dissolved in EtOAc (200 mL), washed with brine, dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:5) to give 9 (2.8 g, 51%) as a white solid, m.p. 162C163 C; 1H-NMR (CDCl3) 7.89 (d, = 7.8 Hz, 1H, Ar-H), 7.70 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.60 (d, = 8.4 Hz, 1H, Ar-H), 7.47 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.21 (t, = 7.2 Hz, 1H, Ar-H), 7.18 (d, = 7.8 Hz, 2H, Ar-H), 2.22 (s, 6H, 2,6-(CH3)2), 2.11 (s, 3H, 3-CH3); 13C-NMR (CDCl3) 154.34, 142.55, 138.58, 133.51, 132.59, 129.99, 129.27, 127.65, 127.23, 126.90, 121.01, 23.38, 18.62; MS (ESI) calcd. for C16H17N2O2S [M + H]+ 301.1, found 301.0. (10) According to the procedures explained for the synthesis of 9, compound 10 were obtained as a colorless solid (6.9 g) in 40% yield, m.p. 150C151 C; 1H-NMR (DMSO-d6) 7.89 (dt, = 7.2, 1.5 Hz, 1H, Ar-H), 7.73 (dd, = 7.2, 1.2 Hz, 2H, Ar-H), 7.36 (t, = 7.2 Hz, 1H, Ar-H), 7.29 (d, = 7.8 Hz, 2H, Ar-H), 2.13 (s, 6H, 2,6-(CH3)2), 2.06 (s, 3H, 3-CH3); 13C-NMR (DMSO-d6) 160.28 (d, calcd. for C16H16FN2O2S [M + H]+ 319.1, found 319.0. (11) Compound 9 (1.0 g, 3.3 mmol) was dissolved in glacial acetic acid (10 mL), and then NBS (0.3 g, 1.65 mmol) was added. After the combination was stirred at room heat for 0.5 h, distilled water (50 mL) was added. The combination was extracted by dichloromethane, washed with brine, dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:10) to give 11 (0.5 g) with a conversion yield of 79% as a white sound, m.p. 150C151C; 1H-NMR (CDCl3) 7.90 (dd, = 7.8, 1.2 Hz, 1H, Ar-H), 7.75 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.69 (dd, = 7.8, 0.6 Hz, 1H, Ar-H), 7.55 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.29 (t, = 7.8 Hz, 1H, Ar-H), 7.19 (d, = 7.8 Hz, 2H, Ar-H), 3.97 (s, 2H, CH2Br), 2.24 (s, 6H, 2,6-(CH3)2); 13C-NMR (CDCl3) 151.86, 142.16, 138.89, 133.69, 132.14, 130.36, 129.51, 128.37, 128.25, 127.79, 121.00, 28.91, 18.95; MS (ESI) calcd. for C16H16BrN2O2S [M + H]+ 379.0 and 381.0, found 381.3 and 383.4. (12) According to the procedures explained for the synthesis of 11, compound 12 were obtained as a colorless solid (0.65 g) in 72% conversion yield, m.p. 185C186 C; 1H-NMR (DMSO-d6) 7.95 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 7.84 (dd, = 10.8, 5.4 Hz, 1H, Ar-H), 7.79 (td, = 10.8, 3.0 Hz, 1H, Ar-H), 7.37 (t, = 8.4 Hz, 1H, Ar-H), 7.29 (d, = 9.0 Hz, 2H, Ar-H), 4.10 (s, 2H, CH2Br), 2.14 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 161.21 (d, calcd.for C16H15BrFN2O2S [M + H]+ 397.0 and 399.0, found 397.2 and 399.1. (13) To a solution of 11 (1.1 g, 2.9 mmol) and 3-iodo-1= 7.8, 1.2 Hz, 1H, Ar-H), 7.80 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.65 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.43 (d, = 7.8 Hz, 1H, Ar-H), 7.25 (t, = 7.2 Hz, 1H, Ar-H), 7.17 (d, calcd. for C21H19IN7O2S [M + H]+ 560.0, found 560.2. (14) Following the procedures explained for the synthesis of 13, compound 14 were obtained as a white solid (1.6 g) in 58% yield, m.p. 243C244 C; 1H-NMR (DMSO-d6) 8.08 (s, 1H, Ar-H), 7.92 (dd, = 11.4, 4.2 Hz, 1H, Ar-H), 7.68 (td, = 13.2, 4.2 Hz, 1H, Ar-H), 7.54 (dd, = 13.2, 7.2 Hz, 1H, Ar-H), 7.26 (dd, = 13.2, 10.2 Hz, 1H, Ar-H), 7.17 (d, = 11.4 Hz, 2H, Ar-H), 5.13 (s, 2H, NCH2), 2.06 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 160.89 (d, calcd. for C21H18FIN7O2S [M + H]+ 578.0, found 578.0. (15a) To a solution of 13 (180 mg, 0.30 mmol) in dioxane (4 mL) and distilled water (1.5 mL) was added 1= 7.8, 1.2 Hz, 1H, Ar-H), 7.81 (td, = 7.8, 1.2 Hz, 2H, Ar-H), 7.65 (td, = 7.8, 0.6 Hz, 1H, Ar-H), 7.57 (d, = 8.4 Hz, 1H, Ar-H), 7.52 (d,.The kinase reaction was carried out in 384-well plate (Corning, Los Altos, MA, USA). Ar-H), 6.97 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 6.85 (dd, = 9.0, Octanoic acid 4.8 Hz, 1H, Ar-H), 5.85 (s, 2H, NH2), 2.04 (s, 6H, 2,6-(CH3)2); MS (ESI) calcd. for C14H14FN2O2S [M ? H]?: 293.1, found: 293.3. (9) A mixture of 7 (5 g, 18.1 mmol), trimethyl orthoacetate (50 mL) and 4? molecular sieve (10 g) was refluxed for 10 h. After cooling to room temp., the combination was concentrated and the residue was dissolved in EtOAc (200 mL), washed with brine, dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:5) to give 9 (2.8 g, 51%) as a white solid, m.p. 162C163 C; 1H-NMR (CDCl3) 7.89 (d, = 7.8 Hz, 1H, Ar-H), 7.70 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.60 (d, = 8.4 Hz, 1H, Ar-H), 7.47 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.21 (t, = 7.2 Hz, 1H, Ar-H), 7.18 (d, = 7.8 Hz, 2H, Ar-H), 2.22 (s, 6H, 2,6-(CH3)2), 2.11 (s, 3H, 3-CH3); 13C-NMR (CDCl3) 154.34, 142.55, 138.58, 133.51, 132.59, 129.99, 129.27, 127.65, 127.23, 126.90, 121.01, 23.38, 18.62; MS (ESI) calcd. for C16H17N2O2S [M + H]+ 301.1, found 301.0. (10) According to the procedures explained for the synthesis of 9, compound 10 were obtained as a colorless solid (6.9 g) in 40% yield, m.p. 150C151 C; 1H-NMR (DMSO-d6) 7.89 (dt, = 7.2, 1.5 Hz, 1H, Ar-H), 7.73 (dd, = 7.2, 1.2 Hz, 2H, Ar-H), 7.36 (t, = 7.2 Hz, 1H, Ar-H), 7.29 (d, = 7.8 Hz, 2H, Ar-H), 2.13 (s, 6H, 2,6-(CH3)2), 2.06 (s, 3H, 3-CH3); 13C-NMR (DMSO-d6) 160.28 (d, calcd. for C16H16FN2O2S [M + H]+ 319.1, found 319.0. (11) Compound 9 (1.0 g, 3.3 mmol) was dissolved in glacial acetic acid (10 mL), and then NBS (0.3 g, 1.65 mmol) was added. After the combination was stirred at room heat for 0.5 h, distilled water (50 mL) was added. The combination was extracted by dichloromethane, washed with brine, dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:10) to give 11 (0.5 g) with a conversion yield of 79% as a white sound, m.p. 150C151C; 1H-NMR (CDCl3) 7.90 (dd, = 7.8, 1.2 Hz, 1H, Ar-H), 7.75 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.69 (dd, = 7.8, 0.6 Hz, 1H, Ar-H), 7.55 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.29 (t, = 7.8 Hz, 1H, Ar-H), 7.19 (d, = 7.8 Hz, 2H, Ar-H), 3.97 (s, 2H, CH2Br), 2.24 (s, 6H, 2,6-(CH3)2); 13C-NMR (CDCl3) 151.86, 142.16, 138.89, 133.69, 132.14, 130.36, 129.51, 128.37, 128.25, 127.79, 121.00, 28.91, 18.95; MS (ESI) calcd. for C16H16BrN2O2S [M + H]+ 379.0 and 381.0, found 381.3 and 383.4. (12) According to the procedures explained for the synthesis of 11, compound 12 were obtained as a colorless solid (0.65 g) in 72% conversion yield, m.p. 185C186 C; 1H-NMR (DMSO-d6) 7.95 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 7.84 (dd, = 10.8, 5.4 Hz, 1H, Ar-H), 7.79 (td, = 10.8, 3.0 Hz, 1H, Ar-H), 7.37 (t, = 8.4 Hz, 1H, Ar-H), 7.29 (d, = 9.0 Hz, 2H, Ar-H), 4.10 (s, 2H, CH2Br), 2.14 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 161.21 (d, calcd.for C16H15BrFN2O2S [M + H]+ 397.0 and 399.0, found 397.2 and 399.1. (13) To a solution of 11 (1.1 g, 2.9 mmol) and 3-iodo-1= 7.8, 1.2 Hz, 1H, Ar-H), 7.80 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.65 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.43 (d, = 7.8 Hz, 1H, Ar-H), 7.25 (t, = 7.2 Hz, 1H, Ar-H), 7.17 (d, calcd. for C21H19IN7O2S [M + H]+ 560.0, found 560.2. (14) Following the procedures explained for the synthesis of 13, compound 14 were obtained as a white solid (1.6 g) in 58% yield, m.p. 243C244 C; 1H-NMR (DMSO-d6) 8.08 (s, 1H, Ar-H), 7.92 (dd, = 11.4, 4.2 Hz, 1H, Ar-H), 7.68 (td, = 13.2, 4.2 Hz, 1H, Ar-H), 7.54 (dd, = 13.2, 7.2 Hz, 1H, Ar-H), 7.26 (dd, = 13.2, 10.2 Octanoic acid Hz, 1H, Ar-H), 7.17 (d, = 11.4 Hz, 2H, Ar-H), 5.13 (s, 2H, NCH2), 2.06 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 160.89 (d, calcd. for C21H18FIN7O2S [M + H]+ 578.0, found 578.0. (15a) To a solution of 13 (180 mg, 0.30 mmol) in dioxane (4 mL).243C244 C; 1H-NMR (DMSO-d6) 8.08 (s, 1H, Ar-H), 7.92 (dd, = 11.4, 4.2 Hz, 1H, Ar-H), 7.68 (td, = 13.2, 4.2 Hz, 1H, Ar-H), 7.54 (dd, = 13.2, 7.2 Hz, 1H, Ar-H), 7.26 (dd, = 13.2, 10.2 Hz, 1H, Ar-H), 7.17 (d, = 11.4 Hz, 2H, Ar-H), 5.13 (s, 2H, NCH2), 2.06 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 160.89 (d, calcd. 7, compound 8 were obtained as a colorless solid (16 g) in 99% yield, m.p. 185C186 C; 1H-NMR (DMSO-d6) 9.44 (s, 1H, SO2NH), 7.21 (td, = 9.0, 3.0 Hz, 1H, Ar-H), 7.07 (td, = 8.4, 1.5 Hz, 1H, Ar-H), 7.01 (d, = 7.8 Hz, 2H, Ar-H), 6.97 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 6.85 (dd, = 9.0, 4.8 Hz, 1H, Ar-H), 5.85 (s, 2H, NH2), 2.04 (s, 6H, 2,6-(CH3)2); MS (ESI) calcd. for C14H14FN2O2S [M ? H]?: 293.1, found: 293.3. (9) A mixture of 7 (5 g, 18.1 mmol), trimethyl orthoacetate (50 mL) and 4? molecular sieve (10 g) was refluxed for 10 h. After cooling to room temp., the combination was concentrated and the residue was dissolved in EtOAc (200 mL), washed with brine, dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:5) to give 9 (2.8 g, 51%) as a white solid, m.p. 162C163 C; 1H-NMR (CDCl3) 7.89 (d, = 7.8 Hz, 1H, Ar-H), 7.70 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.60 (d, = 8.4 Hz, 1H, Ar-H), 7.47 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.21 (t, = 7.2 Hz, 1H, Ar-H), 7.18 (d, = 7.8 Hz, 2H, Ar-H), 2.22 (s, 6H, 2,6-(CH3)2), 2.11 (s, 3H, 3-CH3); 13C-NMR (CDCl3) 154.34, 142.55, 138.58, 133.51, 132.59, 129.99, 129.27, 127.65, 127.23, 126.90, 121.01, 23.38, 18.62; MS (ESI) calcd. for C16H17N2O2S [M + H]+ 301.1, found 301.0. (10) According to the procedures explained for the synthesis of 9, compound 10 were obtained as a colorless solid (6.9 g) in 40% yield, m.p. 150C151 C; 1H-NMR (DMSO-d6) 7.89 (dt, = 7.2, 1.5 Hz, 1H, Ar-H), 7.73 (dd, = 7.2, 1.2 Hz, 2H, Ar-H), 7.36 (t, = 7.2 Hz, 1H, Ar-H), 7.29 (d, = 7.8 Hz, 2H, Ar-H), 2.13 (s, 6H, 2,6-(CH3)2), 2.06 (s, 3H, 3-CH3); 13C-NMR (DMSO-d6) 160.28 (d, calcd. for C16H16FN2O2S [M + H]+ 319.1, found 319.0. (11) Compound 9 (1.0 g, 3.3 mmol) was dissolved in glacial acetic acid (10 mL), and then NBS (0.3 g, 1.65 mmol) was added. After the combination was stirred at room heat for 0.5 h, distilled water (50 mL) was added. The combination was extracted by dichloromethane, washed with brine, dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:10) to give 11 (0.5 g) with a conversion yield of 79% as a white sound, m.p. 150C151C; 1H-NMR (CDCl3) 7.90 (dd, = 7.8, 1.2 Hz, 1H, Ar-H), 7.75 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.69 (dd, = 7.8, 0.6 Hz, 1H, Ar-H), 7.55 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.29 (t, = 7.8 Hz, 1H, Ar-H), 7.19 (d, = 7.8 Hz, 2H, Ar-H), 3.97 (s, 2H, CH2Br), 2.24 (s, 6H, 2,6-(CH3)2); 13C-NMR (CDCl3) 151.86, 142.16, 138.89, 133.69, 132.14, 130.36, 129.51, 128.37, 128.25, 127.79, 121.00, 28.91, 18.95; MS (ESI) calcd. for C16H16BrN2O2S [M + H]+ 379.0 and 381.0, found Octanoic acid 381.3 and 383.4. (12) According to the procedures explained for the synthesis of 11, compound 12 were obtained as a colorless solid (0.65 g) in 72% conversion yield, m.p. 185C186 C; 1H-NMR (DMSO-d6) 7.95 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 7.84 (dd, = 10.8, 5.4 Hz, 1H, Ar-H), 7.79 (td, = 10.8, 3.0 Hz, 1H, Ar-H), 7.37 (t, = 8.4 Hz, 1H, Ar-H), 7.29 (d, = 9.0 Hz, 2H, Ar-H), 4.10 (s, 2H, CH2Br), 2.14 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 161.21 (d, calcd.for C16H15BrFN2O2S [M + H]+ 397.0 and 399.0, found 397.2 and 399.1. (13) To a solution of 11 (1.1 g, 2.9 mmol) and 3-iodo-1= 7.8, 1.2 Hz, 1H, Ar-H), 7.80 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.65 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.43 (d, = 7.8 Hz, 1H, Ar-H), 7.25 (t, = 7.2 Hz, 1H, Ar-H), 7.17 (d, calcd. for C21H19IN7O2S [M + H]+ 560.0, found 560.2. (14) Following the procedures explained for the synthesis of 13, compound 14 were obtained as a white solid (1.6 g) in 58% yield, m.p. 243C244 C; 1H-NMR (DMSO-d6) 8.08 (s, 1H, Ar-H), 7.92 (dd, = 11.4, 4.2 Hz, 1H, Ar-H), 7.68 (td, = 13.2, 4.2 Hz, 1H, Ar-H), 7.54 (dd, = 13.2, 7.2 Hz, 1H, Ar-H), 7.26 (dd, = 13.2, 10.2 Hz, 1H, Ar-H), 7.17 (d, = 11.4 Hz, 2H, Ar-H), 5.13 (s, 2H, NCH2), 2.06 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 160.89 (d, calcd. for C21H18FIN7O2S [M + H]+ 578.0, found 578.0. (15a).In agreement with their high PI3K inhibitory activity, 15a and 15b exhibited high antiproliferative potency against B-cell leukemia SU-DHL-6 cells. the synthesis of 7, compound 8 were obtained as a colorless solid (16 g) in 99% yield, m.p. 185C186 C; 1H-NMR (DMSO-d6) 9.44 (s, 1H, SO2NH), 7.21 (td, = 9.0, 3.0 Hz, 1H, Ar-H), 7.07 (td, = 8.4, 1.5 Hz, 1H, Ar-H), 7.01 (d, = 7.8 Hz, 2H, Ar-H), 6.97 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 6.85 (dd, = 9.0, 4.8 Hz, 1H, Ar-H), 5.85 Octanoic acid (s, 2H, NH2), 2.04 (s, 6H, 2,6-(CH3)2); MS (ESI) calcd. for C14H14FN2O2S [M ? H]?: 293.1, found: 293.3. (9) A mixture of 7 (5 g, 18.1 mmol), trimethyl orthoacetate (50 mL) and 4? molecular sieve (10 g) was refluxed for 10 h. After cooling to room temp., the combination was concentrated and the residue was dissolved in EtOAc (200 mL), washed with brine, dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:5) to give 9 (2.8 g, 51%) as a white solid, m.p. 162C163 C; 1H-NMR (CDCl3) 7.89 (d, = 7.8 Hz, 1H, Ar-H), 7.70 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.60 (d, = 8.4 Hz, 1H, Ar-H), 7.47 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.21 (t, = 7.2 Hz, 1H, Ar-H), 7.18 (d, = 7.8 Hz, 2H, Ar-H), 2.22 (s, 6H, 2,6-(CH3)2), 2.11 (s, 3H, 3-CH3); 13C-NMR (CDCl3) 154.34, 142.55, 138.58, 133.51, 132.59, 129.99, 129.27, 127.65, 127.23, 126.90, 121.01, 23.38, 18.62; MS (ESI) calcd. for C16H17N2O2S [M + H]+ 301.1, found 301.0. (10) According to the procedures explained for the synthesis of 9, compound 10 were obtained as a colorless solid (6.9 g) in 40% yield, m.p. 150C151 C; 1H-NMR (DMSO-d6) 7.89 (dt, = 7.2, 1.5 Hz, 1H, Ar-H), 7.73 (dd, = 7.2, 1.2 Hz, 2H, Ar-H), 7.36 (t, = 7.2 Hz, 1H, Ar-H), 7.29 (d, = 7.8 Hz, 2H, Ar-H), 2.13 (s, 6H, 2,6-(CH3)2), 2.06 (s, 3H, 3-CH3); 13C-NMR (DMSO-d6) 160.28 (d, calcd. for C16H16FN2O2S [M + H]+ 319.1, found 319.0. (11) Compound 9 (1.0 g, 3.3 mmol) was dissolved in glacial acetic acid (10 mL), and then NBS (0.3 g, 1.65 mmol) was added. After the combination was stirred at room heat for 0.5 h, distilled water (50 mL) was added. The combination was extracted by dichloromethane, washed with brine, dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:10) to give 11 (0.5 g) with a conversion yield of 79% as a white sound, m.p. 150C151C; 1H-NMR (CDCl3) 7.90 (dd, = 7.8, 1.2 Hz, 1H, Ar-H), 7.75 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.69 (dd, = 7.8, 0.6 Hz, 1H, Ar-H), 7.55 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.29 (t, = 7.8 Hz, 1H, Ar-H), 7.19 (d, = 7.8 Hz, 2H, Ar-H), 3.97 (s, 2H, CH2Br), 2.24 (s, 6H, 2,6-(CH3)2); 13C-NMR (CDCl3) 151.86, 142.16, 138.89, 133.69, 132.14, 130.36, 129.51, 128.37, 128.25, 127.79, 121.00, 28.91, 18.95; MS (ESI) calcd. for C16H16BrN2O2S [M + H]+ 379.0 and 381.0, found 381.3 and 383.4. (12) Based on the techniques referred to for the formation of 11, substance 12 were attained being a colorless solid (0.65 g) in 72% transformation produce, m.p. 185C186 C; 1H-NMR (DMSO-d6) 7.95 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 7.84 (dd, = 10.8, 5.4 Hz, 1H, Ar-H), 7.79 (td, = 10.8, 3.0 Hz, 1H, Ar-H), 7.37 (t, = 8.4 Hz, 1H, Ar-H), 7.29 (d, = 9.0 Hz, 2H, Ar-H), 4.10 (s, 2H, CH2Br), 2.14 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 161.21 (d, calcd.for C16H15BrFN2O2S [M + H]+ 397.0 and 399.0, found 397.2 and 399.1. (13) To a remedy of 11 (1.1 g, 2.9 mmol) and 3-iodo-1= 7.8, 1.2 Hz, 1H, Ar-H), 7.80 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.65 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.43 (d, = 7.8 Hz, 1H, Ar-H), 7.25 (t, = 7.2.132C133 C; 1H-NMR (DMSO-d6) 8.30 (s, 1H, NH), 8.08 (s, 1H, Ar-H), 7.91 (dd, = 7.2, 2.4 Hz, 1H, Ar-H), 7.81 (brs, 1H, Ar-H), 7.69 (td, = 9.6, 3.0 Hz, 1H, Ar-H), 7.61 (dd, = 9.0, 4.8 Hz, 1H, Ar-H), 7.56 (d, = 8.4 Hz, 1H, Ar-H), 7.44 (t, = 3.0 Hz, 1H, Ar-H), 7.36 (dd, = 8.4, 1.8 Hz, 1H, Ar-H), 7.25 (t, = 7.28Hz, 1H, Ar-H), 7.16 (t, = 7.8 Hz, 2H, Ar-H), 6.54 (s, 1H, 3-CH-indolyl), 5.20 (s, 2H, NCH2), 2.01 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 160.08 (d, calcd. (50 mL) and 4? molecular sieve (10 g) was refluxed for 10 h. After air conditioning to room temperature., the blend was concentrated as well as the residue was dissolved in EtOAc (200 mL), cleaned with brine, dried out more than anhydrous Na2Thus4. After purification and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:5) to provide 9 (2.8 g, 51%) being a white solid, m.p. 162C163 C; 1H-NMR (CDCl3) 7.89 (d, = 7.8 Hz, 1H, Ar-H), 7.70 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.60 (d, = 8.4 Hz, 1H, Ar-H), 7.47 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.21 (t, = 7.2 Hz, 1H, Ar-H), 7.18 (d, = 7.8 Hz, 2H, Ar-H), 2.22 (s, 6H, 2,6-(CH3)2), 2.11 (s, 3H, 3-CH3); 13C-NMR (CDCl3) 154.34, 142.55, 138.58, 133.51, 132.59, 129.99, 129.27, 127.65, 127.23, 126.90, 121.01, 23.38, 18.62; MS (ESI) calcd. for C16H17N2O2S [M + H]+ 301.1, found 301.0. (10) Based on the techniques referred to for the Octanoic acid formation of 9, substance 10 were attained being a colorless solid (6.9 g) in 40% produce, m.p. 150C151 C; 1H-NMR (DMSO-d6) 7.89 (dt, = 7.2, 1.5 Hz, 1H, Ar-H), 7.73 (dd, = 7.2, 1.2 Hz, 2H, Ar-H), 7.36 (t, = 7.2 Hz, 1H, Ar-H), 7.29 (d, = 7.8 Hz, 2H, Ar-H), 2.13 (s, 6H, 2,6-(CH3)2), 2.06 (s, 3H, 3-CH3); 13C-NMR (DMSO-d6) 160.28 (d, calcd. for C16H16FN2O2S [M + H]+ 319.1, found 319.0. (11) Substance 9 (1.0 g, 3.3 mmol) was dissolved in glacial acetic acidity (10 mL), and NBS (0.3 g, 1.65 mmol) was added. Following the blend was stirred at area temperatures for 0.5 h, distilled water (50 mL) was added. The blend was extracted by dichloromethane, cleaned with brine, dried out over anhydrous Na2SO4. After purification and evaporation, the residue was purified by silica gel chromatography (EtOAc/hexane = 1:10) to provide 11 (0.5 g) using a transformation produce of 79% being a white good, m.p. 150C151C; 1H-NMR (CDCl3) 7.90 (dd, = 7.8, 1.2 Hz, 1H, Ar-H), 7.75 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.69 (dd, = 7.8, 0.6 Hz, 1H, Ar-H), 7.55 (td, = 8.4, 1.2 Hz, 1H, Ar-H), 7.29 (t, = 7.8 Hz, 1H, Ar-H), 7.19 (d, = 7.8 Hz, 2H, Ar-H), 3.97 (s, 2H, CH2Br), 2.24 (s, 6H, 2,6-(CH3)2); 13C-NMR (CDCl3) 151.86, 142.16, 138.89, 133.69, 132.14, 130.36, 129.51, 128.37, 128.25, 127.79, 121.00, 28.91, 18.95; MS (ESI) calcd. for C16H16BrN2O2S [M + H]+ 379.0 and 381.0, found 381.3 and 383.4. (12) Based on the techniques referred to for the formation of 11, substance 12 were attained being a colorless solid (0.65 g) in 72% transformation produce, m.p. 185C186 C; 1H-NMR (DMSO-d6) 7.95 (dd, = 8.4, 3.0 Hz, 1H, Ar-H), 7.84 (dd, = 10.8, 5.4 Hz, 1H, Ar-H), 7.79 (td, = 10.8, 3.0 Hz, 1H, Ar-H), 7.37 (t, = 8.4 Hz, 1H, Ar-H), 7.29 (d, = 9.0 Hz, 2H, Ar-H), 4.10 (s, 2H, CH2Br), 2.14 (s, 6H, 2,6-(CH3)2); 13C-NMR (DMSO-d6) 161.21 (d, calcd.for C16H15BrFN2O2S [M + H]+ 397.0 and 399.0, found 397.2 and 399.1. (13) To a remedy of 11 (1.1 g, 2.9 mmol) and 3-iodo-1= 7.8, 1.2 Hz, 1H, Ar-H), 7.80 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.65 (td, = 7.8, 1.2 Hz, 1H, Ar-H), 7.43 (d, = 7.8 Hz, 1H, Ar-H), 7.25 (t, = 7.2 Hz, 1H, Ar-H), 7.17 (d, calcd. for C21H19IN7O2S [M + H]+ 560.0, found 560.2. (14) Following techniques referred to for the formation of 13, substance 14 were attained being a white solid (1.6 g) in 58% produce, m.p. 243C244 C; 1H-NMR (DMSO-d6) 8.08 (s, 1H, Ar-H), 7.92 (dd, = 11.4, 4.2 Hz, 1H, Ar-H), 7.68 (td, = 13.2, 4.2 Hz, 1H, Ar-H), 7.54 (dd, Mouse Monoclonal to MBP tag = 13.2, 7.2 Hz, 1H, Ar-H), 7.26 (dd,.