4.2.4 Ethyl 2-(5-chloro-1-(4-methylbenzyl)-1H-indole-2-carboxamido)benzoate (6i)
Under ice bath conditions, oxalyl chloride (0.85 g, 6.68 mmol, 2 eq) was slowly added dropwise to a solution of 4i (1 g, 3.34 mmol, 1 eq) and DMF (3d) in DCM (20 mL). Once the dropwise addition was complete, the reaction was carried out for 10 min, and then continued at room temperature for 30 min. The resultant mixture was concentrated under reduced pressure to obtain 5-chloro-1-(4-methylbenzyl)-1H-indole-2-carbonyl chloride as a yellow solid, which was used for the further reaction without purification. A solution of ethyl anthranilate (0.55 g, 3.34 mmol, 1 eq) and pyridine (0.79 g, 10.02 mmol, 3 eq) at 0°C in DCM (10 mL) was added to the prepared 5-chloro-1-(4-methylbenzyl)-1H-indole-2-carbonyl chloride, which was stirred for 10 min and then at room temperature for 1 h. The reaction was monitored by TLC. A saturated solution of citric acid and brine (3 × 20 mL) was used to wash the organic phase, followed by drying over Na2SO4, filtration, and concentration under reduced pressure. The residue was purified by flash column chromatography on silica gel (petroleum/ethylacetate) to obtain the intermediate compound 6i as a white solid, yielding 79%. 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H, CONH), 8.49–8.40 (m, 1H, Ar-H), 8.02 (dd, J = 8.0, 1.5 Hz, 1H, Ar-H), 7.88 (d, J = 2.0 Hz, 1H, Ar-H), 7.71–7.64 (m, 1H, Ar-H), 7.62 (d, J = 8.9 Hz, 1H, Ar-H), 7.36–7.21 (m, 3H, Ar-H, Ar-CH=), 7.03 (m, 4H, Ar-H), 5.86 (s, 2H, Ar-CH2), 4.36 (q, J = 7.1 Hz, 2H, CH3CH2-), 2.21 (s, 3H, Ar-CH3), 1.33 (t, J = 7.1 Hz, 3H, CH3CH2-); 13C NMR (100 MHz, DMSO-d6) δ 168.0, 160.2, 140.2, 137.6, 136.8, 135.7, 134.7, 133.1, 131.2, 129.5, 127.2, 126.9, 125.8, 125.2, 124.0, 121.7, 121.4, 118.0, 113.5, 106.0, 61.9, 47.5, 21.1, 14.5; HRMS Calculated for C26H23ClN2O3 [M + H]+ 447.1475, found 447.1465.
Ethyl 2-(1-(4-methylbenzyl)-1 H -indole-2-carboxamido)benzoate (6d)
Target compound 6d were synthesized according to the synthetic procedure given above. white solid, yielding 75%. m.p. 137.4ཞ139.0 ℃; 1H NMR (400 MHz, DMSO-d6) δ 11.70 (s, 1H, CONH), 8.51 (d, J = 8.4 Hz, 1H, Ar-H), 8.03 (dd, J = 7.9, 1.2 Hz, 1H, Ar-H), 7.78 (d, J = 7.9 Hz, 1H, Ar-H), 7.70–7.63 (m, 1H, Ar-H), 7.57 (d, J = 8.4 Hz, 1H, Ar-H), 7.35 (s, 1H, Ar-CH=), 7.33–7.21 (m, 2H, Ar-H), 7.16 (t, J = 7.5 Hz, 1H, Ar-H), 7.03 (m, 4H, Ar-H), 5.87 (s, 2H, Ar-CH2), 4.37 (q, J = 7.1 Hz, 2H, CH3CH2-), 2.21 (s, 3H, Ar-CH3), 1.33 (t, J = 7.1 Hz, 3H, CH3CH2-); 13C NMR (100 MHz, DMSO-d6) δ 168.1, 160.5, 140.6, 139.2, 136.6, 136.0, 134.8, 131.7, 131.2, 129.5, 127.0, 126.2, 125.2, 123.8, 122.7, 121.3, 121.1, 117.5, 111.8, 106.5, 61.9, 47.3, 21.1, 14.45; HRMS Calculated for C26H24N2O3 [M + H]+ 413.1865, found 413.1858.
Ethyl 2-(1-(4-fluorobenzyl)-1 H -indole-3-carboxamido)benzoate (6k)
Target compound 6d were synthesized according to the synthetic procedure given above. white solid, yielding 70%. m.p. 137.4ཞ139.0 ℃; 1H NMR (400 MHz, DMSO-d6) δ 11.25 (s, 1H, CONH), 8.59 (d, J = 8.4 Hz, 1H, Ar-H), 8.26 (s, 1H, N-CH=), 8.25–8.20 (m, 1H, Ar-H), 8.01 (dd, J = 7.9, 1.2 Hz, 1H, Ar-H), 7.68–7.62 (m, 1H, Ar-H), 7.62–7.55 (m, 1H, Ar-H), 7.39–7.32 (m, 2H, Ar-H), 7.28–7.22 (m, 2H, Ar-H), 7.21–7.15 (m, 3H, Ar-H), 5.57 (s, 2H, Ar-CH2), 4.35 (q, J = 7.1 Hz, 2H, CH3CH2-), 1.31 (t, J = 7.1 Hz, 3H, CH3CH2-); 13C NMR (100 MHz, DMSO-d6) δ 168.1, 163.0, 162.1(JC−F = 242.4 Hz), 141.5, 136.8, 134.6, 133.8(JC−F = 3.0 Hz), 132.4, 131.1, 129.9(JC−F = 8.2 Hz), 126.6, 123.2, 122.8, 122.0, 121.4, 121.2, 116.8, 116.0(JC−F = 21.4 Hz), 111.7, 111.1, 61.7, 49.3, 14.5; HRMS Calculated for C25H21FN2O3 [M + H]+ 417.1614, found 417.1606.
Ethyl 2-(5-chloro-1-(4-methylbenzyl)-1 H -indole-3-carboxamido)benzoate (6r)
Target compound 6r were synthesized according to the synthetic procedure given above. white solid, yielding 77%. m.p. 123.7ཞ125.5 ℃; 1H NMR (400 MHz, DMSO-d6) δ 11.17 (s, 1H, CONH), 8.50 (d, J = 8.1 Hz, 1H, Ar-H), 8.31 (s, 1H, N-CH=), 8.21 (d, J = 1.5 Hz, 1H, Ar-H), 8.00 (d, J = 6.8 Hz, 1H, Ar-H), 7.71–7.58 (m, 2H, Ar-H), 7.31–7.11 (m, 6H, Ar-H), 5.54 (s, 2H, Ar-CH2), 4.35 (m, 2H, CH3CH2-), 2.26 (s, 3H, Ar-CH3), 1.31 (t, J = 7.0 Hz, 3H, CH3CH2-); 13C NMR (100 MHz, DMSO-d6) δ 168.1, 162.6, 141.1, 137.5, 135.4, 134.5, 134.3, 133.6, 131.1, 129.8, 127.9, 127.7, 126.8, 123.2, 123.1, 121.5, 120.6, 117.4, 113.4, 110.4, 61.7, 50.1, 21.1, 14.5; HRMS Calculated for C26H23ClN2O3 [M + H]+ 447.1475, found 447.1466.
Ethyl 2-(1-(4-fluorobenzyl)-1 H -indazole-3-carboxamido)benzoate (6t)
Target compound 6t were synthesized according to the synthetic procedure given above. white solid, yielding 73%. m.p. 123.7ཞ125.5 ℃; 1H NMR (400 MHz, DMSO-d6) δ 12.20 (s, 1H, CONH), 8.82 (d, J = 7.8 Hz, 1H, Ar-H), 8.27 (d, J = 8.1 Hz, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.5 Hz, 1H, Ar-H), 7.90 (d, J = 8.6 Hz, 1H, Ar-H), 7.71–7.65 (m, 1H, Ar-H), 7.54–7.42 (m, 3H, Ar-H), 7.36 (t, J = 7.4 Hz, 1H, Ar-H), 7.20 (m, 3H, Ar-H), 5.81 (s, 2H, Ar-CH2), 4.41 (q, J = 7.1 Hz, 2H, CH3CH2-), 1.36 (t, J = 7.1 Hz, 3H, CH3CH2-); 13C NMR (100 MHz, DMSO-d6) δ 167.6, 162.2(JC−F = 242.4 Hz), 160.8, 141.3, 140.8, 137.7, 134.9, 133.1(JC−F = 3.1 Hz), 131.4, 130.3(JC−F = 8.4 Hz), 127.7, 123.7, 123.3, 122.9, 122.1, 120.6, 116.4, 116.0(JC−F = 21.4 Hz), 111.3, 61.9, 52.2, 14.5; HRMS Calculated for C24H20FN3O3 [M + H]+ 418.1567, found 418.1553.
4.2.5 2-(5-chloro-1-(4-methylbenzyl)-1H-indole-2-carboxamido)benzoic acid (7i)
The above compound 6i was dissolved in MeOH:THF solution (2:1) (20 mL), and 10% LiOH solution (15 mL) was added to the reaction mixture. The mixture was refluxed at 50°C for 2 h. After removing the solution under reduced pressure, the residue was placed in water and acidified with concentrated hydrochloric acid. The obtained precipitate was filtered, washed with water, and dried under a vacuum to obtain the target compound 7i as an orange solid, yielding 88%; m.p, 227.2ཞ228.9 ℃; 1H NMR (400 MHz, DMSO-d6) δ 13.84 (s, 1H, Ar-COOH), 12.30 (s, 1H, CONH), 8.65 (d, J = 8.0 Hz, 1H, Ar-H), 8.07 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.76 (d, J = 7.9 Hz, 1H, Ar-H), 7.69–7.61 (m, 1H, Ar-H), 7.58 (d, J = 8.4 Hz, 1H, Ar-H), 7.31 (s, 1H, Ar-CH=), 7.24–7.13 (m, 2H, Ar-H), 7.07-7.00 (m 4H, Ar-H), 5.88 (s, 2H, Ar-CH2), 2.21 (s, 3H, Ar-CH3); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 160.5, 141.5, 139.2, 136.6, 136.0, 134.8, 131.9, 131.8, 129.5, 127.0, 126.2, 125.1, 123.3, 122.6, 121.3, 120.1, 116.8, 111.8, 106.4, 47.3, 21.1; HRMS Calculated for C24H19ClN2O3 [M-H]− 417.1006, found 417.0993.
2-(1-(4-fluorobenzyl)-1 H -indole-2-carboxamido)benzoic acid (7a)
Target compound 7a were synthesized according to the synthetic procedure given above. Light yellow solid; yielding 51%; m.p, 237.1ཞ238.0 ℃; 1H NMR (400 MHz, DMSO-d6) δ 13.82 (s, 1H, Ar-COOH), 12.26 (s, 1H, CONH), 8.64 (d, J = 7.8 Hz, 1H, Ar-H), 8.07 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.77 (d, J = 7.9 Hz, 1H, Ar-H), 7.69–7.63 (m, 1H, Ar-H), 7.60 (d, J = 8.4 Hz, 1H, Ar-H), 7.34–7.30 (m, 2H, Ar-H, Ar-CH=), 7.25–7.14 (m, 4H, Ar-H), 7.14–7.07 (m, 2H, Ar-H), 5.91 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 161.7 (JC−F = 242 Hz), 160.4, 141.4, 139.2, 135.2 (JC−F = 3 Hz), 134.8, 131.8, 131.8, 129.1 (JC−F = 8 Hz), 126.2, 125.3, 123.4, 122.7, 121.4, 120.2, 116.8, 115.7 (JC−F = 21 Hz), 111.7, 106.5, 46.9; HRMS Calculated for C23H17FN2O3 [M-H]− 387.1145, found 387.1147.
2-(1-(4-chlorobenzyl)-1 H -indole-2-carboxamido)benzoic acid (7b)
Target compound 7b were synthesized according to the synthetic procedure given above. white solid, yielding 49%. m.p. 237.5ཞ239.3 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.82 (s, 1H, Ar-COOH), 12.27 (s, 1H, CONH), 8.62 (d, J = 8.4 Hz, 1H, Ar-H), 8.06 (dd, J = 8.0, 1.2 Hz, 1H, Ar-H), 7.77 (d, J = 7.9 Hz, 1H, Ar-H ), 7.64 (t, J = 7.9 Hz, 1H, Ar-H), 7.57 (d, J = 8.4 Hz, 1H, Ar-H), 7.35–7.28 (m, 4H, Ar-H, Ar-CH=), 7.23–7.13 (m, 4H, Ar-H), 5.90 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 160.4, 141.4, 139.2, 138.1, 134.8, 132.1, 131.8, 131.7, 128.9, 128.8, 126.2, 125.3, 123.4, 122.7, 121.5, 120.2, 116.8, 111.6, 106.5, 47.0; HRMS Calculated for C23H17ClN2O3 [M-H]− 403.0849, found 403.0851.
2-(1-(4-methoxybenzyl)-1 H -indole-2-carboxamido)benzoic acid (7c)
Target compound 7c were synthesized according to the synthetic procedure given above. white solid, yielding 43%. m.p. 206.1ཞ207.8 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.83 (s, 1H, Ar-COOH), 12.26 (s, 1H, CONH), 8.67 (d, J = 7.8 Hz, 1H, Ar-H ), 8.08 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.76 (d, J = 7.9 Hz, 1H, Ar-H), 7.69–7.64 (m, 1H, Ar-H), 7.62 (d, J = 8.4 Hz, 1H, Ar-H), 7.36–7.27 (m, 2H, Ar-H, Ar-CH=), 7.24–7.08 (m, 4H, Ar-H), 6.82 (d, J = 8.7 Hz, 2H, Ar-H), 5.85 (s, 2H, Ar-CH2), 3.67 (s, 3H, Ar-OCH3); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 160.5, 158.8, 141.5, 139.2, 134.9, 131.8, 130.9, 128.5, 126.2, 125.1, 123.4, 122.6, 121.3, 120.2, 116.7, 114.3, 111.8, 106.4, 55.4, 46.9; HRMS Calculated for C24H20N2O4 [M-H]− 399.1345, found 399.1345.
2-(1-(4-methylbenzyl)-1 H -indole-2-carboxamido)benzoic acid (7d)
Target compound 7d were synthesized according to the synthetic procedure given above. Light yellow solid, yielding 50%. m.p. 222.3ཞ223.8 ℃;1H NMR (400 MHz, DMSO-d6) δ 12.38 (s, 1H,CONH), 8.65 (d, J = 8.3 Hz, 1H, Ar-H), 8.08 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.76 (d, J = 7.9 Hz, 1H, Ar-H), 7.67–7.60 (m, 1H, Ar-H), 7.57 (d, J = 8.4 Hz, 1H, Ar-H), 7.31 (s, 1H, Ar-CH=), 7.31–7.28 (m 1H, Ar-H) 7.23–7.12 (m, 2H, Ar-H), 7.07-7.00 (m, 4H, Ar-H), 5.88 (s, 2H, Ar-CH2), 2.21 (s, 3H, Ar-CH3); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 160.5, 141.5, 139.2, 136.6, 136.0, 134.7, 131.9, 131.8, 129.5, 127.0, 126.2, 125.1, 123.3, 122.6, 121.3, 120.1, 117.0, 111.8, 106.4, 47.3, 21.1; HRMS Calculated for C24H20N2O3 [M-H]− 383.1396, found 383.1399.
2-(1-(4-(trifluoromethyl)benzyl)-1 H -indole-2-carboxamido)benzoic acid (7e)
Target compound 7e were synthesized according to the synthetic procedure given above. white solid, yielding 43%. m.p. 250.5ཞ252.2 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.85 (s, 1H, Ar-COOH), 12.30 (s, 1H,CONH), 8.60 (d, J = 7.8 Hz, 1H, Ar-H), 8.07 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.80 (d, J = 7.9 Hz, 1H, Ar-H), 7.70–7.60 (m, 3H, Ar-H), 7.57 (d, J = 8.4 Hz, 1H, Ar-H), 7.37 (s, 1H, Ar-CH=), 7.35–7.26 (m, 3H, Ar-H), 7.22–7.18 (m, 2H, Ar-H), 6.02 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 160.3, 144.0, 141.4, 139.2, 134.8, 131.8, 131.8, 128.1(JC−F = 31.6 Hz), 127.5, 126.2, 125.9(JC−F = 3.8 Hz), 125.5, 124.7(JC−F = 270.3 Hz), 123.4, 122.8, 121.6, 120.2, 116.8, 111.5, 106.6, 47.4; HRMS Calculated for C24H17F3N2O3 [M-H]− 437.1113, found 437.1118.
2-(5-chloro-1-(4-fluorobenzyl)-1 H -indole-2-carboxamido)benzoic acid (7f)
Target compound 7f were synthesized according to the synthetic procedure given above. orange solid, yielding 46%. m.p. 213.6ཞ215.2 ℃;1H NMR (400 MHz, DMSO-d6) δ 12.29 (s, 1H, CONH), 8.60 (d, J = 8.0 Hz,1H, Ar-H), 8.06 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.86 (d, J = 2.0 Hz, 1H, Ar-H), 7.67–7.61 (m, 2H, Ar-H), 7.34–7.27 (m, 2H, Ar-H, Ar-CH=), 7.24–7.14 (m, 3H, Ar-H), 7.13–7.06 (m, 2H, Ar-H), 5.89 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 161.8(JC−F = 241.6 Hz), 160.0, 141.2, 137.5, 134.9(JC−F = 3.0 Hz), 134.8, 133.1, 131.8, 129.0(JC−F = 8.2 Hz), 127.3, 126.0, 125.3, 123.6, 121.7, 120.3, 117.0, 115.8(JC−F = 21.3 Hz), 113.5, 105.9, 47.1. HRMS Calculated for C23H16ClFN2O3 [M-H]− 421.0755, found 421.0759.
2-(5-chloro-1-(4-chlorobenzyl)-1H-indole-2-carboxamido)benzoic acid (7g)
Target compound 7g were synthesized according to the synthetic procedure given above. orange solid, yielding 44%. m.p. 234.2ཞ235.4 ℃;1H NMR (400 MHz, DMSO-d6) δ 12.38 (s, 1H, CONH), 8.60 (d, J = 8.4 Hz, 1H, Ar-H), 8.07 (dd, J = 7.9, 1.3 Hz, 1H, Ar-H), 7.88 (d, J = 1.9 Hz, 1H, Ar-H), 7.67–7.60 (m, 2H, Ar-H), 7.35–7.30 (m, 4H, Ar-H, Ar-CH=), 7.21 (t, J = 7.6 Hz, 1H, Ar-H), 7.12 (d, J = 8.4 Hz, 2H, Ar-H), 5.91 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 156.0, 141.2, 137.8, 137.6, 134.7, 133.1, 132.2, 131.8, 129.0, 128.8, 127.3, 126.0, 125.3, 123.5, 121.8, 120.3, 117.2, 113.4, 105.9, 47.2; HRMS Calculated for C23H16Cl2N2O3 [M-H]− 437.0460, found 437.0458.
2-(5-chloro-1-(4-methoxybenzyl)-1 H -indole-2-carboxamido)benzoic acid (7h)
Target compound 7h were synthesized according to the synthetic procedure given above. white solid, yielding 48%. m.p. 214.2ཞ215.4 ℃;1H NMR (400 MHz, DMSO-d6) δ 12.30 (s, 1H, CONH), 8.63 (d, J = 8.4 Hz, 1H, Ar-H), 8.06 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.84 (d, J = 1.9 Hz, 1H, Ar-H), 7.68–7.59 (m, 2H, Ar-H), 7.30 (dd, J = 8.9, 2.1 Hz, 1H, Ar-H), 7.26 (s, 1H, Ar-CH=), 7.24–7.18 (m, 1H, Ar-H), 7.08 (d, J = 8.7 Hz, 2H, Ar-H), 6.85–6.79 (m, 2H, Ar-H), 5.83 (s, 2H, Ar-CH2), 3.66 (s, 3H, Ar-OCH3); 13C NMR (100 MHz, DMSO-d6) δ 170.4, 160.2, 158.9, 141.2, 137.5, 134.8, 133.3, 131.8, 130.6, 128.4, 128.2, 127.3, 125.8, 125.1, 123.6, 121.7, 120.3, 117.0, 114.4, 113.6, 55.5, 47.2; HRMS Calculated for C24H19ClN2O4 [M-H]− 433.0955, found 433.0941.
2-(5-chloro-1-(4-(trifluoromethyl)benzyl)-1 H -indole-2-carboxamido)benzoic acid (7j)
Target compound 7j were synthesized according to the synthetic procedure given above. light yellow solid, yielding 40%. m.p. 240.7ཞ242.0 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.87 (s, 1H, Ar-COOH), 12.32 (s, 1H, CONH), 8.57 (d, J = 8.4 Hz, 1H, Ar-H), 8.06 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.90 (d, J = 1.9 Hz, 1H, Ar-H), 7.69–7.57 (m, 4H, Ar-H), 7.34–7.31 (m, 2H, Ar-H, Ar-CH=), 7.26 (d, J = 8.1 Hz, 2H, Ar-H), 7.23–7.18 (m, 1H, Ar-H), 6.01 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 159.9, 143.6, 141.2, 137.6, 134.8, 133.1, 131.8, 128.2(JC−F = 31.4 Hz), 127.5, 127.3, 126.1, 125.9(JC−F = 3.8 Hz), 125.4, 124.7(JC−F = 270.3 Hz), 123.6, 121.8, 120.3, 117.0, 113.3, 106.0, 47.6; HRMS Calculated for C24H16ClF3N2O3 [M-H]− 471.0723, found 471.0706.
2-(1-(4-fluorobenzyl)-1 H -indole-3-carboxamido)benzoic acid (7k)
Target compound 7k were synthesized according to the synthetic procedure given above. white solid, yielding 39%. m.p. 228.4ཞ230.1 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.72 (s, 1H, Ar-COOH), 11.83 (s, 1H, CONH), 8.75 (d, J = 7.9 Hz, 1H, Ar-H), 8.29–8.22 (m, 2H, Ar-H, N-CH=), 8.05 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.66–7.61 (m, 2H, Ar-H), 7.39–7.35 (m, 2H, Ar-H), 7.29–7.12 (m, 5H, Ar-H), 5.57 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.6, 163.0, 162.1(JC−F = 242.3 Hz), 142.4, 136.8, 134.7, 133.9(JC−F = 2.9 Hz), 132.7, 131.7, 129.9(JC−F = 8.3 Hz), 126.3, 123.2, 122.4, 122.0, 121.2, 120.4, 116.1, 116.0(JC−F = 21.5 Hz), 111.7, 111.5, 49.3; HRMS Calculated for C23H17FN2O3 [M-H]− 387.1145, found 387.1137.
2-(1-(4-chlorobenzyl)-1 H -indole-3-carboxamido)benzoic acid (7l)
Target compound 7l were synthesized according to the synthetic procedure given above. white solid, yielding 47%. m.p. 225.3ཞ226.9 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.71 (s, 1H, Ar-COOH), 11.82 (s, 1H, CONH), 8.75 (d, J = 7.8 Hz, 1H, Ar-H), 8.29–8.22 (m, 2H, Ar-H, N-CH=), 8.05 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.67–7.61 (m, 1H, Ar-H), 7.59–7.57 (m, 1H, Ar-H), 7.44–7.38 (m, 2H, Ar-H), 7.31 (d, J = 8.5 Hz, 2H, Ar-H), 7.28–7.20 (m, 2H, Ar-H), 7.18–7.13 (m, 1H, Ar-H), 5.58 (s, 2H, Ar-CH2); 13C NMR (75 MHz, DMSO-d6) δ 170.6, 162.9, 142.4, 136.9, 136.8, 134.7, 132.8, 131.7, 129.6, 129.2, 126.3, 123.2, 122.5, 122.0, 121.2, 120.4, 116.0, 111.7, 111.5, 49.3; HRMS Calculated for C23H17ClN2O3 [M-H]− 403.0849, found 403.0841.
2-(1-(4-methoxybenzyl)-1 H -indole-3-carboxamido)benzoic acid (7m)
Target compound 7m were synthesized according to the synthetic procedure given above. white solid, yielding 40%. m.p. 204.5ཞ205.9 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.72 (s, 1H, Ar-COOH), 11.81 (s, 1H, CONH), 8.75 (d, J = 7.8 Hz, 1H, Ar-H), 8.24–8.21 (m, 2H, Ar-H, N-CH=), 8.05 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.66–7.62 (m, 2H, Ar-H), 7.30–7.20 (m, 4H, Ar-H), 7.15 (t, J = 7.4, 1H, Ar-H), 6.90 (d, J = 8.7 Hz, 2H, Ar-H), 5.48 (s, 2H, Ar-CH2), 3.71 (s, 3H, Ar-OCH3); 13C NMR (75 MHz, DMSO-d6) δ 170.6, 163.0, 159.3, 142.5, 136.9, 134.7, 132.6, 131.7, 129.5, 129.3, 126.3, 123.1, 122.4, 121.9, 121.1, 120.4, 116.0, 114.6, 111.8, 111.2, 55.5, 49.6; HRMS Calculated for C24H20NO4 [M-H]− 399.1345, found 399.1340.
2-(1-(4-methylbenzyl)-1 H -indole-3-carboxamido)benzoic acid (7n)
Target compound 7n were synthesized according to the synthetic procedure given above. white solid, yielding 44%. m.p. 231.0ཞ232.6 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.71 (s, 1H, Ar-COOH), 11.81 (s, 1H, CONH), 8.75 (dd, J = 8.4, 0.7 Hz, 1H, Ar-H), 8.27–8.19 (m, 2H, Ar-H, N-CH=), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67–7.57 (m, 2H, Ar-H), 7.28–7.18 (m, 4H, Ar-H), 7.18–7.12 (m, 3H, Ar-H), 5.51 (s, 2H, Ar-CH2), 2.26 (s, 3H, Ar-CH3); 13C NMR (75 MHz, DMSO-d6) δ 170.6, 163.0, 142.5, 137.4, 136.9, 134.7, 134.6, 132.7, 131.7, 129.7, 127.7, 126.3, 123.1, 122.4, 121.9, 121.2, 120.4, 116.0, 111.7, 111.2, 49.9, 21.1; HRMS Calculated for C24H20N2O3 [M-H]− 383.1396, found 383.1394.
2-(1-(4-(trifluoromethyl)benzyl)-1 H -indole-3-carboxamido)benzoic acid (7o)
Target compound 7o were synthesized according to the synthetic procedure given above. white solid, yielding 46%. m.p. 231.0ཞ232.6 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.70 (s, 1H, Ar-COOH), 11.83 (s, 1H, CONH), 8.75 (d, J = 8.3 Hz, 1H, Ar-H), 8.30 (s, 1H, N-CH=), 8.28–8.24 (m, 1H, Ar-H), 8.05 (dd, J = 7.9, 1.4 Hz, 1H, Ar-H), 7.72 (d, J = 8.2 Hz, 2H, Ar-H), 7.68–7.61 (m, 1H, Ar-H), 7.58–7.55 (m, 1H, Ar-H), 7.46 (d, J = 8.1 Hz, 2H, Ar-H), 7.28–7.22 (m, 2H, Ar-H), 7.16 (t, J = 7.6 Hz, 1H, Ar-H), 5.72 (s, 2H, Ar-CH2); 13C NMR (75 MHz, DMSO-d6) δ 170.6, 162.9, 142.6, 142.4, 136.9, 134.7, 133.0, 131.7, 128.7(JC−F = 31.6 Hz), 128.2, 126.3, 126.1(JC−F = 3.8 Hz), 124.6(JC−F = 270.5 Hz), 123.3, 122.5, 122.1, 121.3, 120.4, 116.1, 111.7, 111.6, 49.5; HRMS Calculated for C24H17F3N2O3 [M-H]− 437.1113, found 437.1091.
2-(5-chloro-1-(4-fluorobenzyl)-1 H -indole-3-carboxamido)benzoic acid (7p)
Target compound 7p were synthesized according to the synthetic procedure given above. white solid, yielding 38%. m.p. 231.7ཞ233.2 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.73 (s, 1H, Ar-COOH), 11.80 (s, 1H, CONH), 8.69 (d, J = 7.9 Hz, 1H, Ar-H), 8.30 (s, 1H, N-CH=), 8.23 (d, J = 2.0 Hz, 1H, Ar-H), 8.05 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.67–7.62 (m, 2H, Ar-H), 7.38–7.35 (m, 2H, Ar-H), 7.29 (dd, J = 8.8, 2.1 Hz, 1H, Ar-H), 7.23–7.12 (m, 3H, Ar-H), 5.58 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.6, 162.5, 162.1(JC−F = 242.1 Hz), 142.2, 135.4, 134.7, 133.7, 133.6(JC−F = 3.0 Hz), 131.7, 129.9(JC−F = 8.1 Hz), 127.5, 126.9, 123.3, 122.6, 120.5, 116.2, 116.1(JC−F = 21.7 Hz), 113.4, 111.0, 49.5; HRMS Calculated for C23H16ClFN2O3 [M-H]− 421.0755, found 421.0745.
2-(5-chloro-1-(4-methoxybenzyl)-1 H -indole-3-carboxamido)benzoic acid (7q)
Target compound 7q were synthesized according to the synthetic procedure given above. white solid, yielding 40%. m.p. 227.8ཞ229.5 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.73 (s, 1H, Ar-COOH), 11.80 (s, 1H, CONH), 8.69 (d, J = 7.9 Hz, 1H, Ar-H), 8.27 (s, 1H, N-CH=), 8.22 (d, J = 2.0 Hz, 1H, Ar-H), 8.05 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.70–7.61 (m, 2H, Ar-H), 7.28 (dd, J = 8.7, 1.9 Hz, 3H, Ar-H), 7.19–7.12 (m, 1H, Ar-H), 6.91 (d, J = 8.7 Hz, 2H, Ar-H), 5.49 (s, 2H, Ar-CH2), 3.72 (s, 3H, Ar-OCH3); 13C NMR (100 MHz, DMSO-d6) δ 170.6, 162.5, 159.3, 142.2, 135.4, 134.7, 133.6, 131.7, 129.3, 129.2, 127.5, 126.8, 123.2, 122.6, 120.4, 120.4, 116.2, 114.6, 113.5, 110.7, 55.5, 49.8; HRMS Calculated for C24H19ClN2O4 [M-H]− 433.0955, found 433.0946.
2-(5-chloro-1-(4-methylbenzyl)-1 H -indole-3-carboxamido)benzoic acid (7r)
Target compound 7r were synthesized according to the synthetic procedure given above. white solid, yielding 46%. m.p. 187.4ཞ229.5 ℃; 1H NMR (400 MHz, DMSO-d6) δ 14.47 (s, 1H, Ar-COOH), 8.64 (d, J = 8.0 Hz, 1H, Ar-H), 8.32 (d, J = 1.9 Hz, 1H, Ar-H), 8.24 (s, 1H, N-CH=), 8.03 (dd, J = 7.7, 1.5 Hz, 1H, Ar-H), 7.57 (d, J = 8.8 Hz, 1H, Ar-H), 7.39–7.32 (m, 1H, Ar-H), 7.23 (dd, J = 8.8, 2.0 Hz, 1H, Ar-H), 7.18–7.09 (m, 4H, Ar-H), 6.97 (t, J = 7.4 Hz, 1H, Ar-H), 5.51 (s, 2H, Ar-CH2), 2.24 (s, 3H, Ar-CH3); 13C NMR (100 MHz, DMSO-d6) δ 170.5, 162.5, 141.9, 137.4, 135.3, 134.5, 133.1, 131.8, 131.4, 129.7, 128.1, 127.5, 126.5, 123.1, 122.9, 121.5, 120.9, 119.0, 113.2, 111.5, 50.0, 21.1; HRMS Calculated for C24H19ClN2O3 [M-H]− 417.1006, found 417.1004.
2-(5-chloro-1-(4-(trifluoromethyl)benzyl)-1 H -indole-3-carboxamido)benzoic acid (7s)
Target compound 7s were synthesized according to the synthetic procedure given above. white solid, yielding 36%. m.p. 245.2ཞ247.0 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.72 (s, 1H, Ar-COOH), 11.84 (s, 1H, CONH), 8.70 (d, J = 8.3 Hz, 1H, Ar-H), 8.36 (s, 1H, N-CH=), 8.25 (d, J = 2.1 Hz, 1H, Ar-H), 8.05 (dd, J = 7.9, 1.5 Hz, 1H, Ar-H), 7.72 (d, J = 8.2 Hz, 2H, Ar-H), 7.67–7.60 (m, 2H, Ar-H), 7.45 (d, J = 8.1 Hz, 2H, Ar-H), 7.29 (dd, J = 8.8, 2.0 Hz, 1H, Ar-H), 7.18 (t, J = 7.2 Hz, 1H, Ar-H), 5.73 (s, 2H, Ar-CH2).13C NMR (100 MHz, DMSO-d6) δ 170.6, 162.5, 142.3, 142.1, 135.4, 134.6, 134.0, 131.7, 128.8(JC−F = 31.8 Hz), 128.2, 127.5, 127.0, 126.2(JC−F = 3.9 Hz), 124.6(JC−F = 270.5 Hz), 123.4, 122.7, 120.5, 120.4, 116.5, 113.5, 111.2, 49.7; HRMS Calculated for C24H16ClF3N2O3 [M-H]− 471.0723, found 471.0711.
2-(1-(4-fluorobenzyl)-1 H -indazole-3-carboxamido)benzoic acid (7t)
Target compound 7t were synthesized according to the synthetic procedure given above. orange solid, yielding 50%. m.p. 223.3ཞ224.8 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.70 (s, 1H, Ar-COOH), 12.64 (s, 1H, CONH), 8.86 (dd, J = 8.4, 0.8 Hz, 1H, Ar-H), 8.27 (d, J = 8.1 Hz, 1H, Ar-H), 8.08 (dd, J = 7.9, 1.6 Hz, 1H, Ar-H), 7.93 (d, J = 8.6 Hz, 1H, Ar-H), 7.71–7.63 (m, 1H, Ar-H), 7.56–7.43 (m, 3H, Ar-H), 7.40–7.33 (m, 1H, Ar-H), 7.25–7.13 (m, 3H, Ar-H), 5.80 (s, 2H, Ar-CH2); 13C NMR (100 MHz, DMSO-d6) δ 170.0, 162.2(JC−F = 242.7 Hz), 160.9, 141.4, 141.3, 137.8, 134.8, 133.2(JC−F = 2.9 Hz), 131.8, 130.4(JC−F = 8.6 Hz), 127.7, 123.7, 123.1, 122.9, 122.1, 120.1, 116.6, 116.0(JC−F = 21.2 Hz), 111.3, 52.3; HRMS Calculated for C22H16FN3O3 [M-H]− 388.1097, found 388.1091.
2-(1-(4-methoxybenzyl)-1 H -indazole-3-carboxamido)benzoic acid (7u)
Target compound 7u were synthesized according to the synthetic procedure given above. Light yellow solid, yielding 44%. m.p. 254.9ཞ256.1 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.73 (s, 1H, Ar-COOH), 12.66 (s, 1H, CONH), 8.87 (d, J = 8.3 Hz, 1H, Ar-H), 8.26 (d, J = 8.1 Hz, 1H, Ar-H), 8.08 (dd, J = 8.0, 1.2 Hz, 1H, Ar-H), 7.91 (d, J = 8.5 Hz, 1H, Ar-H), 7.68 (t, J = 7.3 Hz, 1H, Ar-H), 7.51 (t, J = 7.6 Hz, 1H, Ar-H), 7.42–7.30 (m, 3H, Ar-H), 7.21 (t, J = 7.5 Hz, 1H, Ar-H), 6.90 (d, J = 8.6 Hz, 2H, Ar-H), 5.72 (s, 2H, Ar-CH2), 3.71 (s, 3H, Ar-OCH3); 13C NMR (100 MHz, DMSO-d6) δ 170.0, 161.0, 159.4, 141.4, 141.1, 137.5, 134.8, 131.8, 129.7, 128.9, 127.5, 123.6, 123.1, 123.0, 122.1, 120.1, 116.5, 114.5, 111.4, 55.5, 52.7; HRMS Calculated for C23H19N3O4 [M-H]− 400.1297, found 400.1296.
2-(1-(4-methylbenzyl)-1 H -indazole-3-carboxamido)benzoic acid (7v)
Target compound 7v were synthesized according to the synthetic procedure given above. orange solid, yielding 46%. m.p. 264.6ཞ265.3 ℃;1H NMR (400 MHz, DMSO-d6) δ 13.72 (s, 1H, Ar-COOH), 12.66 (s, 1H, CONH), 8.87 (d, J = 7.7 Hz, 1H, Ar-H), 8.27 (d, J = 8.1 Hz, 1H, Ar-H), 8.08 (dd, J = 7.9, 1.6 Hz, 1H, Ar-H), 7.89 (d, J = 8.6 Hz, 1H, Ar-H), 7.71–7.64 (m, 1H, Ar-H), 7.53–7.47 (m, 1H, Ar-H), 7.35 (t, J = 7.6 Hz, 1H, Ar-H), 7.30 (d, J = 8.0 Hz, 2H, Ar-H), 7.23–7.18 (m, 1H, Ar-H), 7.15 (d, J = 7.9 Hz, 2H, Ar-H), 5.74 (s, 2H, Ar-CH2), 2.25 (s, 3H, Ar-CH3); 13C NMR (100 MHz, DMSO-d6) δ 170.0, 161.0, 141.4, 141.2, 137.7, 137.6, 134.7, 134.0, 131.8, 129.7, 128.2, 127.6, 123.6, 123.1, 123.0, 122.1, 120.1, 116.6, 111.4, 53.0, 21.1; HRMS Calculated for C23H19N3O3 [M-H]− 384.1348, found 384.1340.
2-(1-(4-(trifluoromethyl)benzyl)-1 H -indazole-3-carboxamido)benzoic acid (7w)
Target compound 7w were synthesized according to the synthetic procedure given above. orange solid, yielding 41%. m.p. 224.5ཞ226.0 ℃;1H NMR (400 MHz, DMSO-d6) δ 12.65 (s, 1H, CONH), 8.85 (dd, J = 8.4, 0.8 Hz, 1H, Ar-H), 8.29 (d, J = 8.2 Hz, 1H, Ar-H), 8.07 (dd, J = 7.9, 1.6 Hz, 1H, Ar-H), 7.91 (d, J = 8.6 Hz, 1H, Ar-H), 7.73 (d, J = 8.2 Hz, 2H, Ar-H), 7.71–7.65 (m, 1H, Ar-H), 7.59–7.50 (m, 3H, Ar-H), 7.41–7.35 (m, 1H, Ar-H), 7.24–7.18 (m, 1H, Ar-H), 5.93 (s, 2H, Ar-CH2);13C NMR (100 MHz, DMSO-d6) δ 170.0, 160.8, 141.7, 141.5, 141.3, 138.1, 134.7, 131.8, 128.9(JC−F = 31.8 Hz), 128.7, 127.9, 126.1(JC−F = 3.6 Hz), 124.6(JC−F = 270.4 Hz), 123.8, 123.1, 122.9, 122.2, 120.2, 116.6, 111.2, 52.4. HRMS Calculated for C23H16F3N3O3 [M-H]− 438.1066, found 438.1049.