4.2.7. Synthesis Procedures and Characterization Data for Individual Compounds
3-Chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a)
Synthesis according to General Procedure A from squaric acid dichloride (4, 3.09 g, 0.02 mol) and 1H-indole (2.39 g, 0.02 mol). The yield of the ocher solid was 3.10 g (67%). IR (KBr): 3193 cm−1 (NH), 1773 cm−1, 1755 cm−1 (C=O), 1616 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 7.20 (ddd, J = 8.1, 7.0, 1.2 Hz, 1H, ArH), 7.22 (ddd, J = 8.1, 7.1, 1.3 Hz, 1H, ArH), 7.51 (dt, J = 8.1, 1.0 Hz, 1H, ArH), 8.20 (d, J = 3.0 Hz, 1H, ArH), 8.30 (ddt, J = 7.9, 1.4, 0.8 Hz, 1H, ArH), 12.27 (s, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 112.3, 121.2, 121.6, 122.9, 128.7 (CH), 105.8, 124.7, 136.4, 171.2, 192.8 (2C), 193.3 (C); C12H6ClNO2 [231.64]; Anal. calcd. for C12H6ClNO2: C 62.22, H 2.61, N 6.05; found C 61.95, H 2.52, N 5.82; MS (EI): m/z (%) = 231 [M]+∙(40), 203 [M+ − 28] (6), 175 [M+ − 56] (100).
3-Chloro-4-(1-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5b)
Synthesis according to General Procedure A from squaric acid dichloride (4, 453 mg, 3.00 mmol) and 1-methyl-1H-indole (0.44 mL, 3.52 mmol). The yield of the yellow solid was 0.21 g (27%). IR (KBr): 1812 cm−1, 1777 cm−1, 1738 cm−1 (C=O, C=C), 1619 cm−1, 1556 cm−1, 1509 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 3.93 (s, 3H, CH3), 7.26 (ddd, J = 8.0, 7.1, 1.1 Hz, 1H, ArH), 7.32 (ddd, J = 8.2, 7.1, 1.3 Hz, 1H, ArH), 7.57 (dt, J = 8.2, 0.9 Hz, 1H, ArH), 8.26 (s, 1H, ArH), 8.29 – 8.32 (m, 1H, ArH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 33.2 (CH3), 110.8, 121.5, 121.9, 123.0, 132.4 (CH), 104.9, 125.2, 137.1, 170.7, 192.8 (2C), 193.2 (C); C13H8ClNO2 [245.66]; Anal. calcd. for C13H8ClNO2: C 63.56, H 3.28, N 5.70; found C 63.44, H 3.23, N 5.59; MS (EI): m/z (%) = 245 [M]+∙(32), 217 [M+ − 28] (2), 189 [M+ − 56] (100).
3-Chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c)
Synthesis according to General Procedure A from squaric acid dichloride (4, 1.53 g, 10.1 mmol) and 5-methoxy-1H-indole (1.51 g, 10.3 mmol). The yield of the green powder was 2.22 g (74%). IR (KBr): 3184 cm−1 (NH), 1800 cm−1, 1776 cm−1, 1741 cm−1 (C=O, C=C), 1631 cm−1, 1543 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 3.78 (s, 3H, CH3), 6.88 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.40 (dd, J = 8.8, 0.6 Hz, 1H, ArH), 7.84 (d, J = 2.5 Hz, 1H, ArH), 8.13 (d, J = 3.1 Hz, 1H, ArH), 11.41 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 60.6 (CH3), 109.2, 117.9, 118.4, 134.5 (CH), 111.0, 111.1, 130.9, 136.7, 160.1, 176.6, 197.9, 198.0 (C); C13H8ClNO3 [261.52]; Anal. calcd. for C13H8ClNO3: C 59.65, H 3.06, N 5.35; found C 59.38, H 3.09, N 5.32; MS (EI): m/z (%) = 261 [M]+∙(45), 233 [M+ − 28] (2), 205 [M+ − 56] (100).
3-Chloro-4-(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5d)
Synthesis according to General Procedure A from squaric acid dichloride (4, 1.51 g, 10.0 mmol) and 2-phenyl-1H-indole (2.08 g, 10.8 mmol). The crude product was purified by column chromatography on silica gel using ethyl acetate/petroleum ether (1/1). The yield of the orange powder was 2.00 g (65%). IR (KBr): 3219 cm−1 (NH), 1769 cm−1, 1743 cm−1 (C=O); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 7.16 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H, ArH), 7.23 (ddd, J = 8.1, 7.1, 1.3 Hz, 1H, ArH), 7.40–7.50 (m, 4H, ArH), 7.54–7.62 (m, 2H, ArH), 8.06 (dd, J = 7.7, 1.0 Hz, 1H, ArH), 12.30 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 111.7, 120.6, 121.7, 122.8, 128.1, 128.6, 129.0 (CH), 102.1, 126.9, 128.3, 131.9, 136.5, 140.0, 173.6, 193.3, 196.2 (C); C18H10ClNO2 [307.73]; Anal. calcd. for C18H10ClNO2: C 70.26, H 3.28, N 4.55; found C 70.08, H 3.26, N 4.46; MS (EI): m/z (%) = 307 [M]+ (45), 279 [M+ − 28] (14), 251 [M+ − 56] (67), 216 [M+ − 91] (100).
3-(5-Bromo-1H-indol-3-yl)-4-chlorocyclobut-3-ene-1,2-dione (5e)
Synthesis according to General Procedure A from squaric acid dichloride (4, 1.97 g, 0.01 mol) and 5-bromo-1H-indole (1.50 g, 0.01 mol). The yield of the ocher powder was 432 mg (14%). IR (KBr): 3460 cm−1 (NH), 1817 cm−1, 1773 cm−1, 1740 cm−1 (C=O, C=C), 1614 cm−1, 1550 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 7.37 (dd, J = 8.7, 2.0 Hz, 1H, ArH), 7.49 (dd, J = 8.6, 0.5 Hz, 1H, ArH), 8.21 (d, J = 3.0 Hz, 1H, ArH), 8.49 (d, J = 2.0 Hz, 1H, ArH), 12.42 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 114.4, 124.0, 125.4, 129.4 (CH), 105.7, 113.6, 126.6, 135.2, 170.8, 193.2 (2C), 194.6 (C); C12H5BrClNO2 [310.53]; MS (EI): m/z (%) = 309 [M]+∙(28), 253 [M+ − 56] (100); Anal. calcd. for C12H5BrClNO2: C 46.41, H 1.62, N 4.51; found C 46.57, H 1.56, N 4.52.
3-Chloro-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5f)
Synthesis according to General Procedure A from squaric acid dichloride (4, 1.21 g, 9.17 mmol) and 2-methyl-1H-indole (1.49 g, 9.84 mmol). The yield of the green powder was 2.25 g (83%). IR (KBr): 3447 cm−1 (NH), 1765 cm−1, 1736 cm−1 (C=O); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 2.80 (s, 3H, CH3), 7.12 (dtd, J = 16.0, 7.2, 1.4 Hz, 2H, ArH), 7.35 (dd, J = 7.2, 1.6 Hz, 1H, ArH), 8.21 (dd, J = 7.4, 1.5 Hz, 1H, ArH), 12.12 (s, 1H, NH); 13C-NMR (100.7 MHz, DMSO-d6): δ (ppm) = 14.1 (CH3), 111.1, 120.7, 121.6, 122.0 (CH), 103.8, 126.6, 136.2, 141.8, 173.4, 192.5, 193.7, 195.2 (C); C13H8O2ClN [245.66]; MS (EI): m/z (%) = 245 [M]+∙(36), 217 [M+ − 28] (5), 189 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 245.02381; found [M]+ = 245.02362.
3,4-Bis(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2a)
Synthesis according to General Procedure F from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 0.262 g, 1.13 mmol) and 1H-indole (0.360 mg, 3.08 mmol). Crystallization from ethanol/toluene yielded a yellow powder (59 mg, 66%).
IR (KBr): 3388 cm−1 (NH), 1766 cm−1, 1704 cm−1 (C=O), 1616 cm−1, 1589 cm−1, 1513 cm−1 (C=C, arom.), 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 7.17 (ddd, J = 8.1, 7.1, 1.1 Hz, 2H), 7.28 (ddd, J = 8.2, 7.1, 1.2 Hz, 2H), 7.58 (dt, J = 8.2, 0.9 Hz, 2H), 7.93 (dt, J = 8.0, 0.9 Hz, 2H), 8.26 (d, J = 3.0 Hz, 2H), 12.44 (s, 2H, NH), 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 112.6, 121.3, 122.6, 123.0, 131.1 (CH), 106.3, 125.0, 136.8, 177.0, 194.8 (C); C20H12N2O2 (312.33); Anal. calcd. for C20H12N2O2: C 76.91, H 3.87, N 8.97; found C 76.41, H 3.70, N 8.87; MS (EI): m/z (%) = 312 [M]+ (35), 256 [M+ − 56] (100); isocratic HPLC: 97.1% at 254 nm, 97.6% at 280 nm, tms = 3.63 min, tm (DMSO) = 1.15 min (ACN/H2O 50:50); gradient HPLC: 95.1% at 254 nm, tms = 11.0 min, tm (DMSO) = 1.25 min; λmax (nm): 271, 331, 410.
3-(5-Bromo-1H-indol-3-yl)-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2b)
Synthesis according to General Procedure C (reaction time: 48 h) from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 256 mg, 1.11 mmol) and 5-bromo-1H-indole (392 mg, 2.00 mmol). The yield of the tawny powder was 166 mg (38%). IR (KBr): 3425 cm−1 (NH), 3127 cm−1 (CH, arom.), 2919 cm−1 (CH, aliph.), 1748 cm−1, 1714 cm−1 (C=O); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 7.19 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H, ArH), 7.30 (ddd, J = 8.2, 7.1, 1.2 Hz, 1H, ArH), 7.41 (dd, J = 8.6, 2.0 Hz, 1H, ArH), 7.51–7.63 (m, 2H, ArH), 7.90 (ddt, J = 8.0, 1.2, 0.6 Hz, 1H, ArH), 8.22 (d, J = 2.0 Hz, 1H, ArH), 8.26 (d, J = 3.0 Hz, 1H, ArH), 8.35 (d, J = 3.1 Hz, 1H, ArH), 12.50 (d, J = 3.2 Hz, 1H, NH), 12.57 (d, J = 3.3 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 112.7, 114.6, 121.4, 122.6, 123.1, 124.8, 125.6, 131.2, 132.0 (CH), 106.0, 106.2, 113.8, 124.9, 127.0, 135.5, 136.9, 176.3, 177.3, 194.6, 194.7 (C); C20H11BrN2O2 [391.22]; Anal. calcd. for C20H11BrN2O2: C 61.40, H 2.83, N 7.16; found C 61.38, H 2.74, N 6.85; MS (EI): m/z (%) = 390 [M]+ (29), 334 [M+ − 56] (100); isocratic HPLC: 99.4% at 254 nm and 99.6% at 280 nm, tms = 5.84 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 273, 329, 346; gradient HPLC: 98.0% at 254 nm, tms = 11.9 min, tm = 1.25 min.
3-(5-Chloro-1H-indol-3-yl)-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2c)
Synthesis according to General Procedure C (reaction time: 20 h) from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 241 mg, 1.04 mmol) and 5-chloro-1H-indole (227 mg, 1.50 mmol). Boiling in ethanol/toluene yielded a yellowish powder (133 mg, 38%). IR (KBr): 3395 cm−1 (NH), 1749 cm−1, 1714 cm−1 (C=O), 1618 cm−1, 1539 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 7.20 (ddd, J = 8.1, 7.0, 1.1 Hz, 1H, ArH), 7.27–7.33 (m, 2H, ArH), 7.57–7.63 (m, 2H, ArH), 7.91 (ddt, J = 8.1, 1.4, 0.7 Hz, 1H, ArH), 8.08 (dt, J = 2.1, 0.6 Hz, 1H, ArH), 8.28 (d, J = 3.1 Hz, 1H, ArH), 8.35 (d, J = 3.1 Hz, 1H, ArH), 12.50 (d, J = 3.1 Hz, 1H, NH), 12.58 (d, J = 3.0 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 112.7, 114.2, 121.4, 121.9, 122.6, 123.1, 123.2, 131.3, 132.2 (CH), 106.2. 106.2, 124.9, 125.8, 126.4, 135.3, 136.9, 176.4, 177.4, 194.7, 194.8 (C); C20H11ClN2O2 [347.77]; Anal. calcd. for C20H11ClN2O2: C 69.27, H 3.20, N 8.08; found C 68.87, H 3.10, N 7.93; MS (EI): m/z (%) = 346 [M]+∙(23), 290 [M+-56] (100); isocratic HPLC: 95.9% at 254 nm and 96.8% at 280 nm, tms = 5.17 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 273, 328 and 347; gradient HPLC: 98.3% at 254 nm, tms = 11.8 min, tm = 1.25 min.
3-(1H-Indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2d)
Synthesis according to General Procedure C (reaction time: 20 h) from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 241 mg, 1.04 mmol) and 5-methoxy-1H-indole (322 mg, 2.19 mmol). The yield of the yellow powder was 40 mg (11%). IR (KBr): 3298 cm−1 (NH), 3144 cm−1 (CH, arom.), 2964 cm−1 (CH, aliph.), 1748 cm−1, 1704 cm−1 (C=O); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.53 (s, 3H, CH3), 6.89 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.15 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H, ArH), 7.27 (ddd, J = 8.2, 7.1, 1.1 Hz, 1H, ArH), 7.31–7.34 (m, 1H, ArH), 7.47 (dd, J = 8.8, 0.5 Hz, 1H, ArH), 7.58 (dt, J = 8.1, 0.9 Hz, 1H, ArH), 7.91 (dt, J = 8.0, 0.9 Hz, 1H, ArH), 8.21 (s, 1H, ArH), 8.25 (s, 1H, ArH), 12.38 (s, 2H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 54.8 (CH3), 104.7, 112.5, 112.8, 113.3, 121.1, 122.5, 122.9, 131.0, 131.4 (CH), 106.2, 106.3, 125.1, 125.5, 131.6, 136.6, 154.5, 176.3, 176.9, 194.4, 195.0 (C); C21H14N2O3 [342.35]; MS (EI): m/z (%) = 342 [M]+ (35), 286 [M+-56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 342.09989; found [M]+ = 342.10005; isocratic HPLC: 98.6% at 254 nm and 98.9% at 280 nm, tms = 3.49 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 229, 273, 336; gradient HPLC: 97.6% at 254 nm, tms = 10.8 min, tm = 1.25 min.
3-[5-(Benzyloxy)-1H-indol-3-yl]-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2e)
Synthesis according to General Procedure C (reaction time: 10 h) from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 262 mg, 1.13 mmol) and 5-benzyloxy-1H-indole (335 mg, 1.50 mmol). The oily product obtained after column chromatography on Al2O3 was taken up in ethyl acetate (3 mL). Upon addition of petroleum ether a tan precipitate appeared, which was subsequently crystallized from petroleum ether/ethyl acetate/ethanol. The yield of the tan powder was 20 mg (5%). IR (KBr): 3405 cm−1 (NH), 1750 cm−1, 1712 cm−1 (C=O), 1628 cm−1, 1540 cm−1, 1512 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 4.73 (s, 2H, CH2), 6.95 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.15 (ddd, J = 8.1, 7.1, 1.0 Hz, 1H, ArH), 7.23–7.37 (m, 6H, ArH), 7.47 (d, J = 8.8 Hz, 2H, ArH), 7.60 (dt, J = 8.2, 0.9 Hz, 1H, ArH), 7.87 (dt, J = 8.0, 1.0 Hz, 1H, ArH), 8.23 (d, J = 3.0 Hz, 1H, ArH), 8.27 (d, J = 3.2 Hz, 1H, ArH), 12.36 (d, J = 3.2 Hz, 1H, NH), 12.44 (d, J = 3.1 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 69.3 (CH2), 106.2, 112.6, 113.4, 113.5, 121.2, 122.5, 123.1, 127.5, 128.3, 131.1, 131.7 (CH), 106.3, 106.4, 125.3, 125.5, 127.3, 127.7, 128.3, 131.8, 136.8, 137.1, 153.7, 176.3, 177.0, 194.5, 195.1 (C); C27H18N2O3 [418.45]; MS (EI): m/z (%) = 418 [M]+ (59), 362 [M+ - 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 418.13119, found [M]+ = 418.13169; isocratic HPLC: 95.2% at 254 nm and 95.5% at 280 nm, tms = 7.26 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 273; gradient HPLC: 95.0% at 254 nm, tms = 12.4 min, tm = 1.25 min.
3-[2-(1H-Indol-3-yl)-3,4-dioxocyclobut-1-ene-1-yl]-1H-indol-5-carbonitrile (2f)
Synthesis according to General Procedure C (reaction time: 20 h) from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 265 mg, 1.14 mmol) and 1H-indole-5-carbonitrile (213 mg, 1.50 mmol). The residue obtained after column chromatography on Al2O3 was crystallized from ethanol/toluene. The yield of the yellow powder was 200 mg (52%). IR (KBr): 3300 cm−1 (NH), 2229 cm−1 (C≡N), 1750 cm−1, 1723 cm−1 (C=O), 1619 cm−1, 1554 cm−1, 1528 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 7.19 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H, ArH), 7.30 (ddd, J = 8.2, 7.0, 1.1 Hz, 1H, ArH), 7.60 (dt, J = 8.1, 0.9 Hz, 1H, ArH), 7.65 (dd, J = 8.5, 1.6 Hz, 1H, ArH), 7.75 (dd, J = 8.5, 0.7 Hz, 1H, ArH), 7.88 (ddt, J = 8.0, 1.3, 0.7 Hz, 1H, ArH), 8.39 (d, J = 3.0 Hz, 1H, ArH), 8.42 (d, J = 3.1 Hz, 1H, ArH), 8.47 (dt, J = 1.5, 0.7 Hz, 1H, ArH), 12.54–12.58 (m, 1H, NH), 12.82–12.86 (m, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 112.8, 114.1, 121.6, 122.6, 123.3, 125.1, 127.8, 131.7, 132.8 (CH), 103.3, 106.2, 106.9, 120.2, 124.9, 125.2, 137.0, 138.6, 175.6, 178.1, 194.5, 195.0 (C); C21H11N3O2 [337.34]; MS (EI): m/z (%) = 337 [M]+ (12), 281 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+∙= 337.08458, found [M]+ = 337.08486; isocratic HPLC: 97.0% at 254 nm and 97.2% at 280 nm, tms = 6.42 min, tm = 1.11 min (ACN/H2O 40:60); λmax (nm): 224, 327 and 346; gradient HPLC: 98.5% at 254 nm, tms = 10.7 min, tm = 1.25 min.
3-(1H-Indol-3-yl)-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2g)
Synthesis according to General Procedure C (reaction time: 19 h) from 3-chloro-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5e, 233 mg, 0.95 mmol) and 1H-indole (233 mg, 1.99 mmol). The yield of the yellow powder was 52 mg (17%). IR (KBr): 3367 cm−1, 3256 cm−1 (NH), 1759 cm−1, 1706 cm−1 (C=O), 1618 cm−1, 1555 cm−1,1522 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 2.55 (s, 3H), 6.98 (ddd, J = 7.9, 7.1, 1.0 Hz, 1H), 7.08 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H), 7.14–7.18 (m, 2H), 7.23 (ddd, J = 8.2, 7.1, 1.1 Hz, 1H), 7.44–7.47 (m, 1H), 7.53 (dt, J = 8.1, 0.9 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.91 (s, 1H), 12.17 (s, 1H), 12.38 (s, 1H); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 13.9 (CH3), 111.6, 112.5, 120.3, 121.1, 121.4, 121.9, 122.1, 123.0, 132.1 (CH), 103.9, 106.6, 125.3, 125.4, 136.4, 136.5, 141.2, 178.4, 178.7, 194.7, 195.8 (C); C21H14N2O2 [326.36]; Anal. calcd. for C21H14N2O2: C 77.29, H 4.32, N 8.58; found C 77.00, H 4.20, N 8.49; MS (EI): m/z (%) = 326 [M]+ (30), 270 [M+ − 56] (100); isocratic HPLC: 96.7% at 254 nm, 96.5% at 280 nm, tms = 3.85 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 273; gradient HPLC: 95.1% at 254 nm, tms = 11.1 min, tm = 1.25 min.
3-(1H-Indol-3-yl)-4-(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2h)
Synthesis according to General Procedure C (reaction time: 21 h) from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 238 mg, 1.03 mmol) and 2-phenyl-1H-indole (430 mg, 3.25 mmol). The yield of the yellow powder was 280 mg (70%). IR (KBr): 3248 cm−1 (NH), 3066 cm−1 (CH, arom.), 1752 cm−1, 1712 cm−1 (C=O); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 6.99–7.11 (m, 2H, ArH), 7.12–7.35 (m, 5H, ArH), 7.38–7.48(m, 2H, ArH), 7.48–7.60 (m, 3H, ArH), 7.75–7.81 (m, 1H, ArH), 7.85 (d, J = 7.9 Hz, 1H, ArH), 12.24 (d, J = 3.0 Hz, 1H, NH), 12.44 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 112.1, 112.4, 120.7, 121.3, 121.5, 122.2, 122.9, 122.9, 128.2, 128.3, 128.6, 132.1 (CH), 102.7, 106.9, 125.1, 126.4, 131.5, 136.5, 136.8, 139.8, 178.9, 180.2, 194.2, 196.8 (C); C26H16N2O2 [388.43]; Anal. calcd. for C26H16N2O2: C 80.40, H 4.15, N 7.21; found C 79.99, H 4.11, N 6.89; MS (EI): m/z (%) = 388 [M]+ (17), 360 [M+ − 28] (8), 332 [M+ − 56] (100); isocratic HPLC: 98.5% at 254 nm and 98.6% at 280 nm, tms = 5.69 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 280, 297, 331; gradient HPLC: 98.0% at 254 nm, tms = 11.7 min, tm = 1.25 min.
3,4-Bis(1-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2i)
Synthesis according to General Procedure C (reaction time: 24 h) from 3-chloro-4-(1-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5b, 248 mg, 1.01 mmol) and 1-methyl-1H-indol (0.190 mL, 1.52 mmol). Due to the poor solubility, the green brown precipitate was boiled successively in ethanol/toluene and then in acetone for purification avoiding column chromatography. The yield of the yellow-green powder was 300 mg (56%). IR (KBr): 1766 cm−1, 1731 cm−1 (C=O), 1615 cm−1, 1576 cm−1, 1561 cm−1, 1517 cm−1 (C=C, arom.); 1H-NMR (600 MHz, chloroform-d): δ (ppm) = 3.93 (s, 6H, CH3), 7.15 (ddd, J = 8.1, 7.1, 1.0 Hz, 2H, ArH), 7.35 (dd, J = 8.2, 7.1 Hz, 2H, ArH), 7.42–7.47 (m, 2H, ArH), 7.79 (dd, J = 8.0, 0.9 Hz, 2H, ArH), 8.01 (s, 2H, ArH); 13C-NMR (151 MHz, Chloroform-d): δ (ppm) = 33.7 (CH3), 110.1, 121.7, 123.5, 123.6, 125.7 (CH), 106.6, 134.1, 137.7, 176.4, 195.4 (C); C22H16N2O2 [340.38]; MS (EI): m/z (%) = 340 [M]+∙(32), 284 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 340.12063, found [M]+∙= 340.12124; isocratic HPLC: 95.1% at 254 nm and 97.4% at 280 nm, tms = 4.53 min, tm = 1.11 min (ACN/H2O 60:40); λmax (nm): 224, 273 and 333; gradient HPLC: 95.1% at 254 nm, tms = 12.8 min, tm = 1.25 min.
3-{1-[3-(Dimethylamino)propyl]-1H-indol-3-yl}-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2k)
To a suspension of 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 235 mg, 1.01 mmol) in anhydrous dichloromethane (10 mL) at 0 °C, anhydrous AlCl3 (400 mg, 3.00 mmol) was added. A solution of 3-(1H-indol-1-yl)-N,N-dimethylpropane-1-amine (0.248 mL, 1.20 mmol) in dichloromethane (10 mL) was slowly added dropwise with stirring,. While stirring was continued for 24 h, the temperature was allowed to rise from 0 °C to RT. The reaction mixture was then poured into water (50 mL) with stirring and filtered. The filtrate was added to ethyl acetate (100 mL). The mixture was washed with sat. Na2CO3 solution (2 × 50 mL), water (2 × 50 mL) and saturated NaCl solution (2 × 50 mL). After drying the organic phase over anhydrous Na2SO4, it was concentrated under reduced pressure. The resulting oily residue was eluted through silica gel with ethanol/ethyl acetate/triethylamine (50/50/1), wherein the yellow phase was collected and concentrated. The residue was then crystallized from acetone and dried in vacuo at 80–90 °C. The yield of yellow powder was 35 mg (9%). IR (KBr): 3426 cm−1 (NH), 1750 cm−1 (C=O), 1615 cm−1, 1553 cm−1, 1521 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d): δ (ppm) = 2.01 (quin, J = 7.1 Hz, 2H, CH2-CH2-CH2-N(CH3)2), 2.23 (s, 6H, CH3), 2.35 (s, br, 2H, CH2-CH2-CH2-N(CH3)2), 4.39 (t, J = 7.0 Hz, 2H, CH2-CH2-CH2-N(CH3)2), 7.18 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H, ArH), 7.22 (ddd, J = 8.1, 7.0, 0.9 Hz, 1H, ArH), 7.32 (dddd, J = 34.1, 8.1, 7.1, 1.2 Hz, 2H, ArH), 7.59 (dt, J = 8.3, 1.0 Hz, 1H, ArH), 7.71 (dt, J = 8.3, 0.9 Hz, 1H, ArH), 7.92 (dt, J = 8.0, 1.0 Hz, 1H, ArH), 7.98 (dt, J = 8.1, 1.0 Hz, 1H, ArH), 8.29 (d, J = 5.3 Hz, 2H, ArH), 12.48 (s, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 26.3 (CH2-CH2-CH2-N(CH3)2), 44.2 (CH2-CH2-CH2-N(CH3)2), 44.6 (2C, CH3), 55.5 (CH2-CH2-CH2-N(CH3)2), 111.1, 112.7, 121.3, 121.6, 122.7, 123.0, 123.1, 123.2, 131.2, 133.8 (CH), 105.6, 106.3, 125.0, 125.6, 136.7, 136.9, 176.4, 177.0, 194.7, 194.8 (C); C25H23N3O2 [397.48]; MS (EI): m/z (%) = 397 [M]+∙(79), 269 [M+∙-128] (100); HRMS (EI) (m/z): Calcd. for [M]+∙= 397.17848, found [M]+∙= 397.17823; isocratic HPLC: 95.1% at 254 nm and 97.4% at 280 nm, tms = 3.13 min, tm = 1.11 min (ACN/triethyl ammonium sulfate buffer pH 2.7: 33:67); λmax (nm): 272, 335 and 345.
3,4-Bis(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2l)
Synthesis according to General Procedure B (reaction time: 30 h) from squaric acid dichloride (4, 302 mg, 2.00 mmol) and 2-methyl-1H-indole (525 mg, 4.01 mmol). Crystallization from ethyl acetate yieled a yellow powder (59 mg, 56%). IR (KBr): 3385 cm−1 (NH), 1760 cm−1, 1720 cm−1 (C=O), 1619 cm−1, 1557 cm−1,1518 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 2.40 (s, 6H, CH3), 6.90 (ddd, J = 8.0, 7.1, 1.0 Hz, 2H, ArH), 7.10 (ddd, J = 8.1, 7.1, 1.1 Hz, 2H, ArH), 7.20–7.25 (m, 2H, ArH), 7.39 (dt, J = 8.1, 0.9 Hz, 2H, ArH), 12.12 (s, 2H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 13.8 (CH3), 104.8, 111.3, 120.4, 120.5, 121.9 (CH), 126.4, 135.9, 141.9, 180.1, 195.6 (C); C22H16N2O2 [340.38]; MS (EI) (m/z): 340 [M]+ (32), 284 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 340.12063, found [M]+ = 340.12098; isocratic HPLC: 99.9% at 254 nm, 99.9% at 280 nm, tms = 3.02 min, tm = 1.25 min (ACN/H2O 50:50); λmax (nm): 275; gradient HPLC: 97.0% at 254 nm, tms = 11.2 min, tm = 1.25 min.
3,4-Bis(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2m)
Synthesis according to General Procedure B (reaction time: 19 h) from squaric acid dichloride (4, 196 mg, 1.30 mmol) and 2-phenyl-1H-indole (567 mg, 2.93 mmol). Crystallization from ethyl acetate yieled an orange powder (72 mg, 12%). IR (KBr): 3350 cm−1 (NH), 1727 cm−1, 1711 cm−1 (C=O), 1548 cm−1,1520 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 7.01 (ddd, J = 8.1, 7.1, 1.0 Hz, 2H), 7.05–7.22 (m, 8H), 7.26–7.32 (m, 4H), 7.36 (dt, J = 8.1, 0.9 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 12.12 (s, 2H, NH); 13C-NMR (100.7 MHz, DMSO-d6): δ (ppm) = 111.7, 120.8, 121.1, 122.7, 127.3, 128.2, 128.5 (CH), 104.2, 126.5, 131.0, 136.5, 141.2, 181.6, 196.0 (C); C32H20N2O2 [464.52]; MS (EI) (m/z): 464 [M]+ (33), 436 [M+ − 28] (12), 420 [M+ − 44] (32), 408 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 464.15193, found [M]+ = 464.15250; isocratic HPLC: 97.4% at 254 nm, 99.3% at 280 nm, tms = 3.90 min, tm = 1.03 min (ACN/H2O 60:40); λmax (nm): 344, 297 and 238; gradient HPLC: 95.1% at 254 nm, tms = 12.4 min, tm = 1.25 min.
3,4-Bis(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2n)
Synthesis according to General Procedure C from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 267 mg, 1.02 mmol) and 5-methoxy-1H-indole (315 mg, 2.14 mmol); yellow powder (Yield: 12%). IR (KBr): 3274 cm−1 (NH), 1748 cm−1, 1715 cm−1 (C=O), 1625 cm−1, 1586 cm−1,1533 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 3.51 (s, 6H, CH3), 6.88 (ddd, J = 8.8, 2.5, 0.3 Hz, 2H, ArH), 7.31–7.35 (m, 2H, ArH), 7.46 (dd, J = 8.8, 0.5 Hz, 2H, ArH), 8.20 (d, J = 0.4 Hz, 2H, ArH), 12.32 (s, 2H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 54.7 (CH3), 104.6, 112.8, 113.2, 131.4 (CH), 106.3, 125.7, 131.5, 154.4, 176.3, 194.6 (C); C22H16N2O4 [372.38]; Anal. calcd. for C22H16N2O4: C 70.96, H 4.33, N 7.52; found C 70.69, H 4.17, N 7.31; MS (EI): m/z (%) = 372 [M]+ (35), 316 [M+ − 56] (100); isocratic HPLC: 96.5% at 254 nm, 98.0% at 280 nm, tms = 3.28 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 277; gradient HPLC: 97.6% at 254 nm, tms = 10.9 min, tm = 1.25 min.
3,4-Bis(5-bromo-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2o)
Synthesis according to General Procedure D from 5-bromo-1H-indole (589 mg, 3.00 mmol) and squaric acid dichloride (4, 151 mg, 1.00 mmol). Crystallization from toluene/acetone yieled a tan powder (37 mg, 8%). IR (KBr): 3390 cm−1 (NH), 1749 cm−1, 1701 cm−1 (C=O); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 7.42 (dd, J = 8.6, 2.0 Hz, 2H, ArH), 7.56 (dd, J = 8.6, 0.6 Hz, 2H, ArH), 8.20 (dd, J = 2.0, 0.5 Hz, 2H, ArH), 8.36 (s, 2H, ArH), 12.64 (s, 2H, NH), 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 114.7, 124.9, 125.7, 132.2 (CH), 105.9, 113.9, 126.9, 135.6, 176.7, 194.6 (C); C20H10Br2N2O2 [470.12]; Anal. calcd. for C20H10Br2N2O2: C 50.88, H 2.56, N 5.93; found C 50.53, H 2.14, N 5.62; MS (EI): m/z (%) = 468 [M]+ (12), 412 [M+ − 56] (100); isocratic HPLC: 97.6% at 254 nm and 98.4% at 280 nm, tms = 9.81 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 327, 278, 228; gradient HPLC: 98.1% at 254 nm, tms = 12.8 min, tm = 1.25 min.
3,3’-(3,4-Dioxocyclobut-1-ene-1,2-diyl)bis(1H-indole-5-carbonitrile) (2p)
Synthesis according to General Procedure B (reaction time: 24 h) from squaric acid dichloride (4, 295 mg, 1.95 mmol) and 1H-indole-5-carbonitrile (570 mg, 4.01 mmol). Crystallization from chloroform/DMF yielded a yellow powder (59 mg, 12%). IR (KBr): 3232 cm−1 (NH), 2230 cm−1 (C≡N), 1764 cm−1, 1727 cm−1 (C=O), 1619 cm−1, 1556 cm−1, 1513 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 7.68 (dd, J = 8.5, 1.7 Hz, 2H, ArH). 7.78 (dd, J = 8.5, 0.8 Hz, 2H, ArH), 8.46 (dt, J = 1.6, 0.7 Hz, 2H, ArH), 8.56 (d, J = 3.1 Hz, 2H, ArH), 12.95 (d, J = 3.6 Hz, 2H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 114.6, 126.4, 128.3, 133.7 (CH), 104.0, 107.1, 120.5, 125.5, 139.2, 177.4, 195.1 (C); C22H10N4O2 [362.35]; MS (EI): m/z (%) = 362 [M]+∙(6), 206 [M+ - 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 362.07983, found [M]+ = 362.07983; isocratic HPLC: 95.3% at 254 nm and 95.9% at 280 nm, tms = 5.11 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 239, 322 and 400; gradient HPLC: 96.9% at 254 nm, tms = 10.5 min, tm = 1.25 min.
3-(1H-Indol-3-yl)-4-(1-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2q)
Synthesis according to General Procedure C from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 295 mg, 1.95 mmol) and 1-methyl-1H-indole (0.274 mL, 2.19 mmol) yielded a yellow powder (88 mg, 26%). IR (KBr): 3422 cm−1 (NH), 3171 cm−1, 1749 cm−1, 1713 cm−1 (C=O), 1616 cm−1, 1551 cm−1, 1524 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 3.98 (s, 3H, CH3), 7.13–7.40 (m, 4H, ArH), 7.62 (ddt, J = 29.0, 8.2, 0.9 Hz, 2H, ArH), 7.89–8.03 (m, 2H, ArH), 8.24–8.30 (m, 1H, ArH), 8.35 (s, 1H, ArH), 12.44 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 33.4 (CH3), 111.0, 112.5, 121.3, 121.5, 122.6, 122.8, 123.1, 131.0, 134.5 (CH), 105.3, 106.4, 125.2, 125.4, 136.7, 137.4, 176.3, 176.9, 194.6, 194.7 (C); C21H14N2O2 [326.36]; Anal. calcd. for C21H14N2O2: C 77.29, H 4.32, N 8.58; found C 76.80, H 4.17, N 8.21; MS (EI): m/z (%) = 231 [M]+ (35), 203 [M+ − 28] (4), 175 [M+ − 56] (100); isocratic HPLC: 99.3% at 254 nm, 99.4% at 280 nm, tms = 5.69 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 222, 272, 333; gradient HPLC: 98.1% at 254 nm, tms = 11.8 min, tm = 1.25 min.
3-(1H-Indol-3-yl)-4-(5-iodo-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2r)
Synthesis according to General Procedure C (reaction time: 20 h) from 3-chloro-4-(1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5a, 234 mg, 1.01 mmol) and 5-iodo-1H-indole (360 mg, 1.48 mmol). Crystallization from ethyl acetate yielded a yellow powder (160 mg, 36%). IR (KBr): 3305 cm−1 (NH), 1751 cm−1, 1699 cm−1 (C=O), 1613 cm−1, 1537 cm−1, 1508 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 7.19 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H, ArH), 7.30 (ddd, J = 8.2, 7.1, 1.2 Hz, 1H, ArH), 7.43 (dd, J = 8.5, 0.6 Hz, 1H, ArH), 7.53–7.62 (m, 2H, ArH), 7.90 (dt, J = 8.0, 1.0 Hz, 1H, ArH), 8.22 (s, 1H), 8.33 (s, 1H, ArH), 8.39 (dd, J = 1.7, 0.5 Hz, 1H, ArH), 12.53 (s, 2H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 112.7, 115.0, 121.4, 122.6, 123.2, 131.1, 131.1, 131.3, 131.6 (CH), 85.5, 105.7, 106.2, 124.9, 127.6, 135.9, 136.9, 176.4, 177.3, 194.7, 194.8 (C); C20H11IN2O2 [438.22]; Anal. calcd. for C20H11IN2O2: C 54.82, H 2.35, N 6.39; found C 54.93, H 2.49, N 6.25; MS (EI): m/z (%) = 438 [M]+∙(33), 382 [M+ − 56] (100); isocratic HPLC: 97.6% at 254 nm and 97.7% at 280 nm, tms = 6.47 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 273, 330 and 345; gradient HPLC: 97.9% at 254 nm, tms = 12.2 min, tm = 1.25 min.
3-(5-Bromo-1H-indol-3-yl)-4-(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2s)
Synthesis according to General Procedure C (reaction time: 24 h) from 3-chloro-4-(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5d, 309 mg, 1.00 mmol) and 5-bromo-1H-indole (297 mg, 1.52 mmol). Crystallization from ethyl acetate yielded an orange powder (130 mg, 28%). IR (KBr): 3253 cm−1 (NH), 1753 cm−1, 1712 cm−1 (C=O), 1615 cm−1, 1548 cm−1,1524 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 7.07–7.39 (m, 7H, ArH), 7.42–7.51 (m, 1H, ArH), 7.51–7.62 (m, 3H, ArH), 7.76 (s, 1H, ArH), 7.93 (d, J = 13.7 Hz, 1H, ArH), 12.34 (s, 1H, NH), 12.51 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 112.1, 114.3, 120.9, 121.5, 123.0, 124.6, 125.3, 128.2, 128.2, 128.6, 132.9 (CH), 102.8, 106.5, 113.9, 126.7, 128.3, 131.4, 135.2, 136.8, 140.0, 179.1, 179.19, 194.3, 196.5 (C); C26H15BrN2O2 [467.32]; Anal. calcd. for C26H15BrN2O2: C 66.82, H 3.24, N 5.99; found C 67.10, H 3.48, N 5.70; MS (EI): m/z (%) = 466 [M]+ (20), 438 [M+ − 28] (10), 410 [M+ − 56] (100); isocratic HPLC: 97.7% at 254 nm, 97.9% at 280 nm, tms = 3.77 min, tm = 1.15 min (ACN/H2O 60:40); λmax (nm): 230, 292; gradient HPLC: 95.7% at 254 nm, tms = 12.5 min, tm = 1.25 min.
3-(5-Bromo-1H-indol-3-yl)-4-(1-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2t)
Synthesis according to General Procedure C (reaction time: 22 h) from 3-chloro-4-(1-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5b, 189 mg, 0.77 mmol) and 5-bromo-1H-indole (221 mg, 1.13 mmol). Crystallization from dichloromethane/ethyl acetate/ethanol yielded a yellow powder (190 mg, 61%). IR (KBr): 3420 cm−1 (NH), 1749 cm−1, 1712 cm−1 (C=O), 1615 cm−1, 1548 cm−1,1521 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 3.99 (s, 3H, CH3), 7.25 (ddd, J = 8.1, 7.1, 1.0 Hz, 1H, ArH), 7.32–7.45 (m, 2H, ArH), 7.55 (dd, J = 8.7, 0.5 Hz, 1H, ArH), 7.67 (dt, J = 8.3, 0.9 Hz, 1H, ArH), 7.89–7.99 (m, 1H, ArH), 8.26–8.32 (m, 2H, ArH), 8.44 (s, 1H), 12.58 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 33.4 (CH3), 111.1, 114.5, 121.7, 122.8, 123.2, 124.9, 125.6, 132.0, 134.7 (CH), 105.1, 106.0, 113.8, 125.3, 127.1, 135.5, 137.5, 176.1, 176.6, 194.5, 194.6 (C); C21H13BrN2O2 [405.25]; MS (EI): m/z (%) = 404 [M]+ (23), 350 [M+∙-56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 404.01549, found [M]+ = 404.01552; isocratic HPLC: 99.4% at 254 nm, 99.7% at 280 nm, tms = 4.38 min, tm = 1.15 min (ACN/H2O 60:40); λmax (nm): 275, 328, and 344; gradient HPLC: 99.0% at 254 nm, tms = 12.8 min, tm = 1.25 min.
3-(1-Methyl-1H-indol-3-yl)-4-(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2u)
Synthesis according to General Procedure D from 3-chloro-4-(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5d, 310 mg, 1.01 mmol) and 1-methyl-1H-indole (190 mL, 1.52 mmol). Crystallization from petroleum ether/acetone yielded a yellow powder (105 mg, 26%). IR (KBr): 3438 cm−1 (NH), 1767 cm−1, 1732 cm−1 (C=O), 1616 cm−1, 1565 cm−1,1533 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.70 (s, 3H, CH3), 7.06–7.13 (m, 2H, ArH), 7.18–7.30 (m, 6H, ArH), 7.47 (dt, J = 8.2, 0.9 Hz, 1H, ArH), 7.53–7.61 (m, 4H, ArH), 12.49 (s, 1H), 7.69 (s, 1H, ArH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 33.1 (CH3), 110.7, 112.0, 120.7, 121.4, 121.7, 122.3, 122.9, 122.9, 128.2, 128.2, 128.6, 135.7 (CH), 102.9, 105.7, 125.6, 126.8, 131.7, 136.7, 136.9, 139.1, 178.5, 178.9, 194.2, 196.5 (C); C27H18N2O2 [402.45]; C 80.58, H 6.96, N 4.51; found C 80.22, H 7.06, N 4.66; MS (EI): m/z (%) = 402 [M]+ (14), 374 [M+ − 28] (4), 346 [M+ − 56] (100); isocratic HPLC: 98.2% at 254 nm, 98.6% at 280 nm, tms = 4.05 min, tm = 1.15 min (ACN/H2O 60:40); λmax (nm): 297, 334; gradient HPLC: 98.1% at 254 nm, tms = 12.6 min, tm = 1.25 min.
3-(5-Methoxy-1H-indol-3-yl)-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2v)
Synthesis according to General Procedure C (reaction time: 48 h) from 3-chloro-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5e, 257 mg, 1.05 mmol) and 5-methoxy-1H-indole (149 mg, 1.01 mmol). Crystallization from ethanol/toluene yielded a yellow powder (70 mg, 20%). IR (KBr): 3191 cm−1 (NH), 1756 cm−1, 1710 cm−1 (C=O), 1622 cm−1, 1554 cm−1,1524 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 2.57 (s, 3H, CH3), 3.32 (s, 3H, OCH3), 6.81 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 6.94 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H, ArH), 7.10–7.19 (m, 3H, ArH), 7.38 – 7.46 (m, 2H, ArH), 8.00 (s, 1H, ArH), 12.13 (s, 1H, NH), 12.29 (s, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 13.9, 54.4 (CH3), 104.2, 111.4, 113.0, 113.2, 120.3, 120.9, 121.8, 132.2 (CH), 104.0, 106.6, 125.7, 156.0, 131.4, 136.2, 140.9, 154.6, 177.8, 179.0, 194.4, 196.0 (C); C22H16N2O3 [356.38]; MS (EI): m/z (%) = 356 [M]+ (30), 300 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 356.11554, found [M]+ = 356.11599; isocratic HPLC: 98.3% at 254 nm, 99.5% at 280 nm, tms = 3.52 min, tm = 1.11 min (ACN/H2O 50:50), λmax: 276 nm; gradient HPLC: 95.4% at 254 nm, tms = 11.0 min, tm = 1.25 min.
3-(2-Methyl-1H-indol-3-yl)-4-(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2w)
Synthesis according to General Procedure C (reaction time: 28 h) from 3-chloro-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5e, 244 mg, 0.99 mmol) and 2-phenyl-1H-indole (403 mg, 3.02 mmol). Crystallization from acetone yielded a yellow powder (50 mg, 13%). IR (KBr): 3467 cm−1 (NH), 1764 cm−1, 1732 cm−1 (C=O), 1616 cm−1, 1552 cm−1,1522 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 2.42 (s, 3H, CH3), 6.80 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H, ArH), 6.92 (d, J = 8.0 Hz, 1H, ArH), 6.96–7.28 (m, 9H, ArH), 7.51 (dt, J = 8.1, 0.9 Hz, 1H, ArH), 7.63–7.70 (m, 1H, ArH), 11.85 (s, 1H, NH), 12.34 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 13.7 (CH3), 111.0, 112.0, 120.2, 120.3, 120.9, 121.2, 121.7, 122.9, 127.1, 128.0, 128.1 (CH), 103.7, 105.6, 125.7, 127.2, 131.0, 136.1, 136.5, 141.2, 141.9, 180.4, 181.2, 195.2, 196.4 (C); C27H18N2O2 [402.45] MS (EI): m/z (%) = 402 [M]+∙ (22), 374 [M+ − 28] (100), 346 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 402.13628, found [M]+ = 402.13693; isocratic HPLC: 98.8% at 254 nm, 98.8% at 280 nm, tms = 6.23 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 285, 233; gradient HPLC: 98.5% at 254 nm, tms = 11.9 min, tm = 1.25 min.
3-(5-Bromo-1H-indol-3-yl)-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2x)
Synthesis according to General Procedure C (reaction time: 26 h) from 3-chloro-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5e, 245 mg, 1.00 mmol) and 5-bromo-1H-indole (364 mg, 1.86 mmol). Crystallization from acetone yielded a yellow powder (70 mg, 17%). IR (KBr): 3387 cm−1 (NH), 1754 cm−1, 1714 cm−1 (C=O), 1615 cm−1, 1550 cm−1,1524 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 2.59 (s, 3H, CH3), 7.00 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H, ArH), 7.09 (dt, J = 7.9, 0.9 Hz, 1H, ArH), 7.18 (ddd, J = 8.1, 7.1, 1.2 Hz, 1H, ArH), 7.37 (dd, J = 8.6, 2.0 Hz, 1H, ArH), 7.44–7.54 (m, 2H, ArH), 7.83 (s, 1H, ArH), 8.14 (d, J = 1.9 Hz, 1H, ArH), 12.24 (s, 1H, NH), 12.50 (s, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 14.0 (CH3), 111.6, 114.5, 120.4, 121.1, 121.9, 124.6, 125.5, 133.0 (CH), 103.7, 106.2, 113.8, 124.9, 127.2, 135.2, 136.4, 141.6, 178.0, 178.7, 194.6, 195.6 (C); C21H13BrN2O2 [405.25]; Anal. calcd. for C21H13BrN2O2: C 62.24, H 3.23, N 6.91; found C 62.37, H 3.02, N 6.66; MS (EI): m/z (%) = 404 [M]+ (28), 348 [M+ − 56] (100); isocratic HPLC: 99.3% at 254 nm, 98.6% at 280 nm, tms = 6.00 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 276, 328, 334; gradient HPLC: 95.3% at 254 nm, tms = 11.7 min, tm = 1.25 min.
3-(1-Methyl-1H-indol-3-yl)-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2y)
Synthesis according to General Procedure C (reaction time: 22 h) from 3-chloro-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5e, 221 mg, 0.90 mmol) and 1-methyl-1H-indole (0.268 mL, 2.15 mmol) yielded a yellow powder (16 mg, 5%). IR (KBr): 3446 cm−1 (NH), 3295 cm−1 (CH, arom.), 1764 cm−1, 1735 cm−1 (C=O), 1611 cm−1, 1563 cm−1,1538 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 2.51 (s, 3H, CH3), 3.91 (s, 3H, N-CH3), 6.97 (ddd, J = 8.1, 7.1, 1.0 Hz, 1H, ArH), 7.09 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H, ArH), 7.16 (ddd, J = 8.1, 7.1, 1.1 Hz, 1H, ArH), 7.21 (dt, J = 7.9, 0.9 Hz, 1H, ArH), 7.29 (ddd, J = 8.2, 7.1, 1.1 Hz, 1H, ArH), 7.45 (dt, J = 8.1, 0.9 Hz, 1H, ArH), 7.60 (dt, J = 8.3, 0.9 Hz, 1H, ArH), 7.72 (d, J = 8.0 Hz, 1H, ArH), 8.07 (s, 1H, ArH), 12.17 (s, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 14.0 (CH3), 33.3 (N-CH3), 111.0, 111.5, 120.3, 121.0, 121.6, 121.9, 123.0, 135.4 (CH), 104.0, 105.5, 122.2, 125.6, 125.7, 136.3, 137.2, 141.0, 177.9, 178.2, 194.57, 195.7 (C); C22H16N2O2 [340.38]; MS (EI): m/z (%) = 340 [M]+ (34), 284 [M+-56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 340.12063, found [M]+ = 340.10261; isocratic HPLC: 99.6% at 254 nm, 99.7% at 280 nm, tms = 6.56 min, tm (DMSO)= 1.11 min (ACN/H2O 50:50); λmax (nm): 274; gradient HPLC: 97.3% at 254 nm, tms = 11.9 min, tm = 1.25 min.
3-(5-Bromo-1-methyl-1H-indol-3-yl)-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2z)
Synthesis according to General Procedure D from 3-chloro-4-(2-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5e, 246 mg, 1.02 mmol) and 5-bromo-1-methyl-1H-indole (316 mg, 1.50 mmol). Crystallization from ethanol/toluene yielded an orange powder (138 mg, 32%). IR (KBr): 3422 cm−1 (NH), 1767 cm−1, 1716 cm−1 (C=O), 1607 cm−1, 1557 cm−1,1529 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 2.56 (s, 3H, CH3), 3.88 (s, 3H, N-CH3), 6.99 (ddd, J = 8.0, 7.0, 1.1 Hz, 1H, ArH), 7.11–7.24 (m, 2H, ArH), 7.37–7.50 (m, 2H, ArH), 7.59 (d, J = 8.7 Hz, 1H, ArH), 7.98 (s, 1H, ArH), 8.01 (d, J = 1.9 Hz, 1H, ArH), 12.23 (s, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 14.2 (CH3), 33.5 (N-CH3), 111.6, 113.2, 120.4, 121.1, 122.1, 124.8, 125.4, 136.3 (CH), 103.9, 105.2, 114.3, 125.5, 127.5, 136.1, 136.5, 141.4, 177.4, 178.6, 194.6, 195.6 (C); C22H15BrN2O2 [419.28]; C 63.02, H 3.61, N 6.68; found C 63.15, H 3.58, N 6.34; MS (EI): m/z (%) = 418 [M]+ (25), 362 [M+ − 56] (100); isocratic HPLC: 96.2% at 254 nm, 98.1% at 280 nm, tms = 4.48 min, tm = 1.15 min (ACN/H2O 60:40); λmax (nm): 277, 334; gradient HPLC: 95.6% at 254 nm, tms = 12.9 min, tm = 1.25 min.
3-(5-Methoxy-1H-indol-3-yl)-4-(2-phenyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2aa)
Synthesis according to General Procedure C (reaction time: 65 h) from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 225 mg, 0.86 mmol) and 2-phenyl-1H-indole (272 mg, 1.42 mmol). Crystallization from ethanol/toluene yielded a yellow powder (62 mg, 17%). IR (KBr): 3257 cm−1 (NH), 1751 cm−1, 1708 cm−1 (C=O), 1624 cm−1, 1547 cm−1,1523 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.32 (s, 3H, O-CH3), 6.75 (dd, J = 8.8, 2.5 Hz, 1H), 7.03 (ddd, J = 8.0, 6.9, 1.0 Hz, 1H, ArH), 7.21–7.36 (m, 6H, ArH), 7.38–7.43 (m, 1H, ArH), 7.53–7.62 (m, 4H, ArH), 12.22 (s, 1H, NH), 12.42 (s, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 54.4 (CH3), 111.9, 112.8, 113.1, 120.7, 121.1, 122.9, 127.4, 128.0, 128.4, 128.5, 131.3 (CH), 102.8, 104.1, 106.9, 125.8, 131.4, 132.3, 136.6, 139.3, 154.7, 178.3, 180.7, 193.9, 197.2 (C); C27H18N2O3 [418.45]; MS (EI): m/z (%) = 418 [M]+∙ (17), 390 [M+ − 56] (6), 362 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 418.13119, found [M]+ = 418.13126; isocratic HPLC: 97.1% at 254 nm, 97.2% at 280 nm, tms = 5.21 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 294, 344, 377; gradient HPLC: 95.1% at 254 nm, tms = 11.6 min, tm = 1.25 min.
3-(5-Fluoro-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ab)
Synthesis according to General Procedure C (reaction time: 20 h) from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 260 mg, 0.99 mmol) and 5-fluoro-1H-indole (201 mg, 1.49 mmol). Crystallization from ethanol/DMF yielded a tan powder (184 mg, 51%). IR (KBr): 3443 cm−1 (NH), 1747 cm−1, 1712 cm−1 (C=O), 1629 cm−1, 1538 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.58 (s, 3H, OCH3), 6.91 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.14 (td, J = 9.1, 2.6 Hz, 1H, ArH), 7.31–7.37 (m, 1H, ArH), 7.48 (dd, J = 8.8, 0.5 Hz, 1H, ArH), 7.59 (ddd, J = 8.8, 4.7, 0.5 Hz, 1H, ArH), 7.75 (dd, J = 10.1, 2.6 Hz, 1H, ArH), 8.24 (d, J = 3.1 Hz, 1H, ArH), 8.31 (d, J = 3.2 Hz, 1H, ArH), 12.39 (d, J = 3.3 Hz, 1H, NH), 12.50 (d, J = 3.1 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 55.0 (O-CH3), 104.8, 107.6 (d, 2JC,F = 24.9 Hz), 111.3 (d, 2JC,F = 26.0 Hz), 113.0, 113.5, 113.8 (d, 3JC,F = 10.0 Hz), 113.9, 132.6 (CH), 106.2, 106.7 (d, 4JC,F = 4.2 Hz), 113.8, 125.6, 126.0 (d, 3JC,F = 10.9 Hz), 133.4, 154.7, 157.8 (d, 1JC,F = 234.4 Hz), 175.9, 177.0, 194.5, 194.9 (C); C21H13FN2O2 [360.34]; MS (EI): m/z (%) = 360 [M]+ (35), 304 [M+∙-56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 360.09047, found [M]+ = 360.09119; isocratic HPLC: 97.2% at 254 nm and 98.2% at 280 nm, tms = 3.68 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 276; gradient HPLC: 98.4% at 254 nm, tms = 11.1 min, tm = 1.25 min.
3-(5-Chloro-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ac)
Synthesis according to General Procedure C (reaction time: 24 h) from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 262 mg, 1.00 mmol) and 5-chloro-1H-indole (220 mg, 1.45 mmol). The dark green precipitate was crystallized from ethanol/toluene to yield a yellow powder (195 mg, 52%). IR (KBr): 3428 cm−1 (NH), 1750 cm−1, 1715 cm−1 (C=O), 1624 cm−1, 1540 cm−1, 1517 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 3.59 (s, 3H, O-CH3), 6.93 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.26–7.35 (m, 2H, ArH), 7.50 (d, J = 8.8 Hz, 1H, ArH), 7.61 (dd, J = 8.6, 0.5 Hz, 1H, ArH), 8.07 (d, J = 2.1 Hz, 1H, ArH), 8.24 (d, J = 3.1 Hz, 1H, ArH), 8.33 (d, J = 3.2 Hz, 1H, ArH), 12.41 (d, J = 3.1 Hz, 1H, NH), 12.55 (d, J = 3.1 Hz, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 55.0 (O-CH3), 104.9, 113.0, 113.5, 114.1, 121.8, 123.0, 131.6, 132.2 (CH), 106.2, 106.2, 125.5, 125.7, 126.5, 131.7, 135.2, 154.8, 175.7, 177.2, 194.4, 195.0 (C); C21H13ClN2O3 [376.80]; Anal. calcd. for C21H13ClN2O3: C 66.94, H 3.48, N 7.43; found C 66.65, H 3.38, N 7.13; MS (EI): m/z (%) = 376 [M]+ (28), 320 [M+∙-56] (100); isocratic HPLC: 98.3% at 254 nm and 98.9% at 280 nm, tms = 4.87 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 277; gradient HPLC: 95.6% at 254 nm, tms = 11.5 min, tm = 1.25 min.
3-(5-Bromo-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ad)
Synthesis according to General Procedure F from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 262 mg, 1.00 mmol) and 5-bromo-1H-indole (585 mg, 2.98 mmol). Crystallization from petroleum ether/ethyl acetate yielded a yellow powder (84 mg, 20%). IR (KBr): 3418 cm−1 (NH), 1746 cm−1, 1700 cm−1 (C=O), 1530 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.58 (s, 3H, CH3), 6.92 (ddd, J = 8.8, 2.5, 0.4 Hz, 1H, ArH), 7.28–7.34 (m, 1H, ArH), 7.40 (dd, J = 8.6, 2.0 Hz, 1H, ArH), 7.48 (dd, J = 8.8, 0.5 Hz, 1H, ArH), 7.55 (dd, J = 8.6, 0.5 Hz, 1H, ArH), 8.19–8.23 (m, 2H, ArH), 8.32 (d, J = 0.4 Hz, 1H, ArH), 12.45 (s, 2H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 54.9 (CH3), 104.7, 112.9, 113.4, 114.5, 124.8, 125.5, 131.54, 132.0 (CH), 105.9, 106.1, 113.6, 125.4, 127.3, 131.6, 135.4, 154.7, 175.5, 177.1, 194.3, 194.9 (C); C21H13BrN2O2 [421.25]; Anal. calcd. for C21H13BrN2O2: C 59.88, H 3.11, N 6.65; found C 59.83, H 3.04, N 6.40; MS (EI): m/z (%) = 422 [M]+ (25), 366 [M+ − 56] (100); isocratic HPLC: 99.4% at 254 nm, 99.7% at 280 nm, tms = 5.24 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 278; gradient HPLC: 99.4% at 254 nm, tms = 11.8 min, tm = 1.25 min.
3-(5-Iodo-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-en-1,2-dione (2ae)
Synthesis according to General Procedure C (reaction time: 24 h) from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 262 mg, 1.00 mmol) and 5-iodo-1H-indole (362 mg, 1.45 mmol). The green precipitate crystallized from ethanol/toluene to yield a tan powder (200 mg, 43%). IR (KBr): 3400 cm−1 (NH), 1750 cm−1, 1703 cm−1 (C=O), 1626 cm−1, 1539 cm−1, 1512 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 3.57 (s, 3H, O-CH3), 6.93 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.30 (d, J = 2.5 Hz, 1H, ArH), 7.44 (dd, J = 8.6, 0.6 Hz, 1H, ArH), 7.47–7.60 (m, 2H, ArH), 8.17 (d, J = 3.0 Hz, 1H), 8.31 (d, J = 3.2 Hz, 1H, ArH), 8.37 (d, J = 1.7 Hz, 1H, ArH), 12.40 (d, J = 3.2 Hz, 1H, NH), 12.52 (d, J = 3.0 Hz, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 54.9 (O-CH3), 104.9, 113.0, 113.4, 114.9, 131.0, 131.1, 131.6 (2C) (CH), 85.3, 105.7, 106.2, 125.5, 127.7, 131.7, 135.8, 154.7, 175.7, 177.2, 194.4, 195.0 (C); C21H13IN2O3 [468.25]; MS (EI): m/z (%) = 468 [M]+ (33), 412 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 467.99654, found [M]+∙= 467.99523; isocratic HPLC: 95.6% at 254 nm and 96.8% at 280 nm, tms = 6.01 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 256, 309; gradient HPLC: 95.6% at 254 nm, tms = 12.0 min, tm = 1.25 min.
3-(5-Methoxy-1H-indol-3-yl)-4-(1-methyl-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2af)
Synthesis according to General Procedure C (reaction time: 65 h) from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 245 mg, 0.90 mmol) and 1-methyl-1H-indole (0.190 mL, 1.52 mmol) yielded a yellow powder (56 mg, 18%). IR (KBr): 3416 cm−1 (NH), 1751 cm−1, 1708 cm−1 (C=O), 1624 cm−1, 1530 cm−1,1514 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.55 (s, 3H, N-CH3), 3.98 (s, 3H, O-CH3), 6.90 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.20 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H, ArH), 7.34 (ddd, J = 8.2, 7.1, 1.1 Hz, 1H, ArH), 7.41 - 7.44 (m, 1H, ArH), 7.47 (dd, J = 8.8, 0.5 Hz, 1H, ArH), 7.65 (dt, J = 8.3, 0.9 Hz, 1H, ArH), 7.92 (dt, J = 8.0, 1.0 Hz, 1H), 8.25 (s, 1H, ArH), 8.32 (s, 1H, ArH), 12.35 (s, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 33.3 (N-CH3), 54.8 (O-CH3), 104.7, 110.9, 112.9, 113.2, 121.4, 122.7, 123.0, 131.3, 134.3 (CH), 105.2, 106.3, 125.4, 125.8, 131.5, 137.3, 154.6, 175.6, 176.8, 194.3, 194.8 (C); C22H16N2O3 [356.38] C 74.15, H 4.53, N 7.86; found C 74.01, H 4.44, N 7.61; MS (EI): m/z (%) = 356 [M]+ (30), 300 [M+ − 56] (100); isocratic HPLC: 99.6% at 254 nm, 99.7% at 280 nm, tms = 5.12 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 275, 351; gradient HPLC: 97.3% at 254 nm, tms = 11.8 min, tm = 1.25 min.
3-(5-Bromo-1-methyl-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ag)
Synthesis according to General Procedure C (reaction time: 20 h) from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 265 mg, 1.01 mmol) and 5-bromo-1-methyl-1H-indole (319 mg, 1.52 mmol). The yellow precipitate crystallized from ethanol/toluene to yield a yellow powder (215 mg, 49%). IR (KBr): 3400 cm−1 (NH), 1751 cm−1, 1714 cm−1 (C=O), 1623 cm−1, 1609 cm−1,1547 cm−1, 1519 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.60 (s, 3H, CH3), 3.97 (s, 3H, O-CH3), 6.92 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.43 (d, J = 2.4 Hz, 1H, ArH), 7.45–7.50 (m, 2H, ArH), 7.63 (dd, J = 8.7, 0.5 Hz, 1H, ArH), 8.21 (dd, J = 2.0, 0.6 Hz, 1H, ArH), 8.31–8.37 (m, 2H, ArH), 12.41 (s, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 34.1 (CH3), 55.5 (O-CH3), 105.3, 113.6, 113.9, 125.6, 126.0, 132.0, 135.7 (CH), 105.5, 106.8, 114.7, 126.3, 127.9, 132.2, 136.6, 155.4, 175.4, 177.6, 194.7, 195.3 (C); C22H15BrN2O3 [435.28] MS (EI): m/z (%) = 434 [M]+ (27), 406 [M+ − 28] (1), 378 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 434.02606, found [M]+ = 434.02622; isocratic HPLC: 97.9% at 254 nm, 98.0% at 280 nm, tms = 3.83 min, tm = 1.15 min (ACN/H2O 60:40); λmax (nm): 279, 349; gradient HPLC: 98.7% at 254 nm, tms = 12.5 min, tm = 1.25 min.
3-[2-(5-Methoxy-1H-indol-3-yl)-3,4-dioxocyclobut-1-en-1-yl]-1H-indole-5-carbonitrile (2ah)
Synthesis according to General Procedure C (reaction time: 24 h) from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 258 mg, 0.99 mmol) and 1H-indole-5-carbonitrile (220 mg, 1.55 mmol). The yellow precipitate was crystallized from ethanol/toluene to yield a yellow powder (202 mg, 56%). IR (KBr): 3370 cm−1 (NH), 2220 cm−1 (C≡N), 1752 cm−1, 1719 cm−1 (C=O), 1620 cm−1, 1553 cm−1, 1520 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 3.58 (s, 3H, CH3), 6.94 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.28 (d, J = 2.5 Hz, 1H, ArH), 7.45–7.55 (m, 1H, ArH), 7.65 (dd, J = 8.5, 1.6 Hz, 1H, ArH), 7.77 (dd, J = 8.4, 0.8 Hz, 1H, ArH), 8.37 (dd, J = 20.9, 3.1 Hz, 2H, ArH), 8.47 (dd, J = 1.5, 0.7 Hz, 1H, ArH), 12.47 (d, J = 3.2 Hz, 1H, NH), 12.82 (d, J = 2.9 Hz, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 55.0 (O-CH3), 104.9, 113.0, 113.6, 114.0, 125.6, 127.1, 132.0, 132.8 (CH), 103.2, 106.2, 106.9, 120.1, 125.3, 125.5, 131.8, 138.5, 154.9, 174.9, 177.9, 194.2, 195.2 (C); C21H13N3O3 [367.36]; MS (EI): m/z (%) = 367 [M]+ (25), 311 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+∙= 367.09514, found [M]+ = 367.09491; isocratic HPLC: 97.5% at 254 nm and 97.5% at 280 nm, tms = 5.79 min, tm = 1.11 min (ACN/H2O 40:60); λmax (nm): 266, 308; gradient HPLC: 96.0% at 254 nm, tms = 10.4 min, tm = 1.25 min.
3-(7-Chloro-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ai)
Synthesis according to General Procedure C (reaction time: 48 h) from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 267 mg, 1.02 mmol) and 7-chloro-1H-indole (228 mg, 1.50 mmol). The yellow precipitate recrystallized from ethanol/toluene to yield a yellow powder (199 mg, 52%). IR (KBr): 3420 cm−1, 3383 cm−1 (NH), 1754 cm−1, 1718 cm−1 (C=O), 1620 cm−1, 1586 cm−1,1540 cm−1, 1513 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.54 (s, 3H, CH3), 6.91 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.17 (t, J = 7.9 Hz, 1H, ArH), 7.23 (d, J = 2.4 Hz, 1H, ArH), 7.37 (dd, J = 7.6, 0.9 Hz, 1H, ArH), 7.48 (d, J = 8.9 Hz, 1H, ArH), 7.90 (dt, J = 7.9, 0.8 Hz, 1H, ArH), 8.11 (d, J = 3.0 Hz, 1H, ArH), 8.30 (d, J = 3.2 Hz, 1H, ArH), 12.42 (d, J = 3.2 Hz, 1H, NH), 12.79 (d, J = 3.0 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 54.9 (CH3), 104.8, 113.0, 113.6, 121.5, 122.2, 122.6, 131.3, 132.0 (CH) 106.2, 107.4, 116.8, 125.5, 127.2, 131.8, 133.6, 154.8, 175.6, 177.9, 194.1, 195.4 (C); C21H13ClN2O3 [376.80]; C 66.94, H 3.48, N 7.43; found C 67.05, H 3.36, N 7.37; MS (EI): m/z (%) = 376 [M]+ (32), 320 [M+ − 56] (100); isocratic HPLC: 97.5% at 254 nm, 98.0% at 280 nm, tms = 5.69 min, tm = 1.15 min (ACN/H2O 50:50); λmax (nm): 274; gradient HPLC: 97.8% at 254 nm, tms = 11.8 min, tm = 1.25 min.
3-(7-Bromo-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2aj)
Synthesis according to General Procedure D from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 270 mg, 1.03 mmol) and 7-bromo-1H-indole (294 mg, 1.50 mmol). Crystallization from ethanol/toluene yielded a yellow powder (162 mg, 37%). IR (KBr): 3325 cm−1 (NH), 1749 cm−1, 1708 cm−1 (C=O), 1619 cm−1, 1536 cm−1,1514 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.54 (s, 3H, CH3), 6.91 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.12 (t, J = 7.9 Hz, 1H, ArH), 7.22 (d, J = 2.4 Hz, 1H, ArH), 7.46–7.54 (m, 2H, ArH), 7.93 (dt, J = 8.0, 0.8 Hz, 1H, ArH), 8.08 (d, J = 3.2 Hz, 1H, ArH), 8.30 (d, J = 3.2 Hz, 1H, ArH), 12.43 (d, J = 3.2 Hz, 1H, NH), 12.63 (d, J = 3.1 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 54.9 (CH3), 104.8, 113.0, 113.6, 121.9, 122.5, 125.7, 131.2, 132.0 (CH), 104.9, 106.2, 107.5, 125.4, 126.9, 131.8, 135.1, 154.8, 175.7, 177.9, 194.1, 195.4 (C); C21H13BrN2O3 [421.25]; C 59.88, H 3.11, N 6.65; found C 59.92, H 3.01, N 6.65; MS (EI): m/z (%) = 420 [M]+∙ (26), 364 [M+ − 56] (100); isocratic HPLC: 97.7% at 254 nm, 98.5% at 280 nm, tms = 5.69 min, tm = 1.15 min (ACN/H2O 50:50); λmax (nm): 275; gradient HPLC: 98.2% at 254 nm, tms = 12.0 min, tm = 1.25 min.
3-(7-Iodo-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ak)
Synthesis according to General Procedure D from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 263 mg, 1.01 mmol) and 7-iodo-1H-indole (244 mg, 1.00 mmol). Crystallization from acetone yielded a yellow powder (111 mg, 24%). IR (KBr): 3413 cm−1 (NH), 1754 cm−1, 1721 cm−1 (C=O), 1608 cm−1, 1544 cm−1,1512 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.53 (s, 3H, CH3), 6.90 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 6.93–6.99 (m, 1H, ArH), 7.21 (d, J = 2.4 Hz, 1H, ArH), 7.48 (d, J = 8.8 Hz, 1H, ArH), 7.68 (dd, J = 7.4, 1.0 Hz, 1H, ArH), 7.92 (dt, J = 8.0, 0.9 Hz, 1H, ArH), 8.04 (d, J = 3.2 Hz, 1H, ArH), 8.28 (d, J = 3.2 Hz, 1H, ArH), 12.33 (d, J = 3.1 Hz, 1H, ArH), 12.42 (d, J = 3.1 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 54.9 (CH3), 104.8, 113.0, 113.6, 122.5, 122.9, 131.0, 131.8, 132.1 (CH), 77.8, 106.2, 107.6, 125.4, 125.8, 131.9, 138.6, 154.8, 175.9, 177.8, 194.2, 195.4 (C); C21H13IN2O3 [468.25]; C 53.87, H 2.80, N 5.98; found C 54.00, H 2.58, N 5.78; MS (EI): m/z (%) = 468 [M]+∙ (33), 364 [M+ − 56] (100); isocratic HPLC: 99.4% at 254 nm, 99.8% at 280 nm, tms = 7.13 min, tm = 1.15 min (ACN/H2O 50:50); λmax (nm): 275; gradient HPLC: 96.8% at 254 nm, tms = 12.2 min, tm = 1.25 min.
3-(7-Ethyl-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2al)
Synthesis according to General Procedure D from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 267 mg, 1.02 mmol) and 7-ethyl-1H-indole (0.205 mL, 1.50 mmol). Crystallization from acetone yielded a yellow powder (62 mg, 16%). IR (KBr): 3400 cm−1, 3379 cm−1 (NH), 1753 cm−1, 1714 cm−1 (C=O), 1612 cm−1, 1587 cm−1,1536 cm−1, 1514 cm−1 (C=C, arom.); 1H-NMR (400 MHz, DMSO-d6): δ (ppm) = 1.29 (t, J = 7.5 Hz, 3H, CH2-CH3), 2.94 (q, J = 7.5 Hz, 2H, CH2-CH3), 3.51 (s, 3H, CH3), 6.89 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.03–7.14 (m, 2H, ArH), 7.29 (d, J = 2.5 Hz, 1H, ArH), 7.47 (d, J = 8.8 Hz, 1H, ArH), 7.70 (dd, J = 7.2, 1.8 Hz, 1H, ArH), 8.12 (d, J = 3.2 Hz, 1H, ArH), 8.23 (d, J = 3.1 Hz, 1H, ArH), 12.34 (d, J = 3.2 Hz, 1H, NH), 12.44 (d, J = 3.1 Hz, 1H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 14.6 (CH2-CH3), 54.8 (OCH3), 23.6 (CH2-CH3), 104.8, 112.9, 113.4, 120.1, 121.4, 121.8, 130.5, 131.5 (CH), 106.3, 106.8, 125.2, 125.6, 128.2, 131.7, 135.4, 154.6, 176.4, 177.2, 194.5, 195.1 (C); C23H18N2O3 [370.41]; MS (EI): m/z (%) = 370 [M]+ (30), 314 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+ = 370.13119, found [M]+ = 370.13142; isocratic HPLC: 95.5% at 254 nm, 96.7% at 280 nm, tms = 5.71 min, tm = 1.15 min (ACN/H2O 50:50); λmax (nm): 350, 273; gradient HPLC: 96.2% at 254 nm, tms = 11.9 min, tm = 1.25 min.
3-(6-Bromo-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2am)
Synthesis according to General Procedure D from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 267 mg, 1.02 mmol) and 6-bromo-1H-indole (293 mg, 1.49 mmol). Crystallization from ethanol/toluene yielded a yellow powder (42 mg, 10%). IR (KBr): 3307 cm−1 (NH), 1751 cm−1, 1710 cm−1 (C=O), 1611 cm−1, 1529 cm−1,1510 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.56 (s, 3H, O-CH3), 6.91 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.27–7.34 (m, 2H, ArH), 7.48 (d, J = 8.8 Hz, 1H, ArH), 7.77 (d, J = 1.7 Hz, 1H, ArH), 7.89 (d, J = 8.5 Hz, 1H, ArH), 8.20 (s, 1H, ArH), 8.28 (s, 1H, ArH), 12.43 (s, 2H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 54.9 (CH3), 104.8, 113.0, 113.52, 115.2, 124.0, 124.4, 131.8 (2C) (CH), 106.2, 106.5, 115.7, 124.2, 125.6, 131.7, 137.7, 154.8, 175.7, 177.5, 194.3, 195.2 (C); C21H13BrN2O3 [421.25]; Anal. calcd. for C21H13BrN2O3: C 59.88, H 3.11, N 6.65; found C 59.59, H 3.04, N 6.59; MS (EI): m/z (%) = 420 [M]+ (27), 364 [M+ − 56] (100); isocratic HPLC: 97.5% at 254 nm, 98.2% at 280 nm, tms = 4.25 min, tm = 1.15 min (ACN/H2O 50:50); λmax (nm): 278; gradient HPLC: 95.0% at 254 nm, tms = 12.0 min, tm = 1.25 min.
3-(4-Bromo-1H-indol-3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-en-1,2-dione (2an)
Synthesis according to General Procedure D from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 267 mg, 1.02 mmol) and 4-bromo-1H-indole (0.188 mL, 1.50 mmol). Crystallization from ethyl acetate yielded a yellow powder (20 mg, 5%). IR (KBr): 3238 cm−1 (NH), 1769 cm−1, 1713 cm−1 (C=O), 1623 cm−1, 1528 cm−1,1517 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 2.96 (s, 3H, CH3), 6.76 (dd, J = 8.8, 2.5 Hz, 1H, ArH), 7.10–7.18 (m, 1H, ArH), 7.26–7.34 (m, 2H, ArH), 7.37–7.45 (m, 1H, ArH), 7.58 (dd, J = 8.2, 0.8 Hz, 1H, ArH), 7.91 (s, 1H, ArH), 8.40 (s, 1H, ArH), 12.37 (s, 2H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 53.8 (CH3), 111.9, 113.2, 113.4, 113.6, 123.9, 124.6, 128.4, 132.7 (CH), 103.0, 105.3, 107.3, 125.1, 125.9, 131.7, 137.8, 154.9, 178.6, 183.6, 194.7, 198.0 (C); C21H13BrN2O3 [421.25] MS (EI): m/z (%) = 420 [M]+ (26), 364 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+∙= 420.01041, found [M]+ = 420.01102; isocratic HPLC: 97.2% at 254 nm, 97.8% at 280 nm, tms = 3.19 min, tm = 1.15 min (ACN/H2O 45:55); λmax (nm): 276, 364; gradient HPLC: 96.2% at 254 nm, tms = 10.9 min, tm = 1.25 min.
3-(5-Bromo-1H-indol-3-yl)-4-(5-methoxy-1-methyl-1H-indol-3-yl)cyclobut-3-en-1,2-dione (2ao)
Synthesis according to General Procedure D from 3-(5-bromo-1H-indol-3-yl)-4-chlorocyclobut-3-ene-1,2-dione (5f, 314 mg, 1.01 mmol) and 5-methoxy-1-methyl-1H-indole (193 mg, 1.20 mmol). Crystallization from chloroform/DMF yielded a yellow powder (80 mg, 18%). IR (KBr): 3422 cm−1 (NH), 1751 cm−1, 1712 cm−1 (C=O), 1625 cm−1, 1544 cm−1,1518 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.58 (s, 3H, CH3), 3.97 (d, J = 0.4 Hz, 3H, CH3), 6.95–7.01 (m, 1H, ArH), 7.34 (d, J = 2.4 Hz, 1H, ArH), 7.37–7.43 (m, 1H, ArH), 7.56 (ddd, J = 11.3, 8.8, 0.5 Hz, 2H, ArH), 8.21–8.28 (m, 2H, ArH), 8.41 (t, J = 0.5 Hz, 1H, ArH), 12.61 (d, J = 2.9 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 33.6, 55.0 (CH3), 105.2, 112.1, 112.9, 114.5, 124.9, 125.6, 132.1, 135.0 (CH), 105.0, 106.1, 113.7, 126.0, 127.2, 132.6, 135.4, 155.1, 175.4, 176.5, 194.2, 194.9 (C); C22H15BrN2O3 [435.28]; Anal. calcd. for C22H15BrN2O3: C 60.71, H 3.47, N 6.44; found C 60.52, H 3.19, N 6.32; MS (EI): m/z (%) = 434 [M]+ (30), 378 [M+ − 56] (100); isocratic HPLC: 98.3% at 254 nm, 99.0% at 280 nm, tms = 4.09 min, tm = 1.15 min (ACN/H2O 60:40); λmax (nm): 229, 278, 350; gradient HPLC: 97.0% at 254 nm, tms = 12.7 min, tm = 1.25 min.
3-(5-Bromo-1H-indol-3-yl)-4-(5-hydroxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ap)
To a suspension of 3-(5-bromo-1H-indol- 3-yl)-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ad, 100 mg, 0.237 mmol) in anhydrous dichloromethane (10 mL) was added a solution of boron tribromide (1 M in dichloromethane, 4.00 mL, 4 mmol). The reaction was stirred at rt for 15 h. Under ice cooling, water (50 mL) was carefully added and the mixture was stirred for a further hour. The suspension was extracted with ethyl acetate (2 × 100 mL). The combined organic layers were washed with water (2 × 50 mL) and saturated NaCl solution (1 × 50 mL) and dried with anhydrous Na2SO4. After subsequent evaporation to dryness, the resulting residue was crystallized from petroleum ether/acetone to yield a yellow powder (55 mg, 57%). IR (KBr): 3422 cm−1 (NH), 1751 cm−1, 1712 cm−1 (C=O), 1625 cm−1, 1544 cm−1,1518 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 6.78 (dd, J = 8.7, 2.4 Hz, 1H, ArH), 7.23 (d, J = 2.4 Hz, 1H, ArH), 7.39 (d, J = 8.8 Hz, 1H, ArH), 7.41 (dd, J = 8.6, 2.0 Hz, 1H, ArH), 7.55 (d, J = 8.6 Hz, 1H, ArH), 8.14 (d, J = 3.1 Hz, 1H, ArH), 8.24 (d, J = 3.2 Hz, 1H, ArH), 8.30 (d, J = 1.9 Hz, 1H, ArH), 9.14 (s, 1H, ArH), 12.30 (d, J = 3.1 Hz, 1H, NH), 12.55 (d, J = 3.1 Hz, 1H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 107.3, 113.1, 113.3, 114.6, 124.9, 125.6, 131.4, 132.0 (CH), 105.7, 106.1, 113.7, 125.9, 127.2, 131.0, 135.5, 152.7, 175.4, 177.4, 194.4, 194.9 (C); C20H11BrN2O3 [407.2]; Anal. calcd. for C20H11BrN2O3: C 58.99, H 2.72, N 6.88; found C 58.61, H 2.74, N 6.35; MS (EI): m/z (%) = 406 [M]+ (29), 350 [M+ − 56] (100); isocratic HPLC: 96.4% at 254 nm, 98.5% at 280 nm, tms = 5.35 min, tm = 1.15 min (ACN/H2O 40:60); λmax (nm): 255, 309; gradient HPLC: 95.0% at 254 nm, tms = 10.4 min, tm = 1.25 min.
3,4-Bis(5-iodo-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2aq)
Synthesis according to General Procedure E from squaric acid dichloride (4, 150 mg, 0.99 mmol) anf 5-iodo-1H-indole (729 mg, 3.00 mmol). Crystallization from ethyl acetate/ethanol yielded an orange powder (70 mg, 12%). IR (KBr): 3375 cm−1 (NH), 1755 cm−1, 1695 cm−1 (C=O), 1529 cm−1, 1505 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 7.42–7.47 (m, 2H, ArH), 7.57 (dd, J = 8.5, 1.7 Hz, 2H, ArH), 8.30 (s, 2H, ArH), 8.34 (d, J = 1.8 Hz, 2H, ArH), 12.62 (s, 2H, NH); 13C-NMR (151 MHz, DMSO-d6): δ (ppm) = 115.5, 131.6, 131.6, 132.2 (CH), 86.1, 106.0, 128.0, 136.4, 177.1, 195.1 (C); C20H10I2N2O2 [564.12]; Anal. calcd. for C20H10I2N2O2: C 42.58, H 1.79, N 4.97; found C 45.52, H 1.52, N 4.76; MS (EI): m/z (%) = 564 [M]+∙(33), 508 [M+ − 56] (100); isocratic HPLC: 97.1% at 254 nm and 98.0% at 280 nm, tms = 5.03 min, tm = 1.11 min (ACN/H2O 60:40); λmax (nm): 280, 329, 344; gradient HPLC: 96.5% at 254 nm, tms = 13.4 min, tm = 1.25 min.
3-[5-(Benzyloxy)-1H-indol-3-yl]-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (2ar)
Synthesis according to General Procedure F from 3-chloro-4-(5-methoxy-1H-indol-3-yl)cyclobut-3-ene-1,2-dione (5c, 274 mg, 1.05 mmol) and 5-(Benzyloxy)-1H-indole (670 mg, 3.00 mmol). Crystallization from petroleum ether/ethylacetate yielded an orange powder (35 mg, 7%). IR (KBr): 3307 cm−1 (NH), 1747 cm−1, 1711 cm−1 (C=O), 1624 cm−1, 1536 cm−1, 1508 cm−1 (C=C, arom.); 1H-NMR (600 MHz, DMSO-d6): δ (ppm) = 3.47 (s, 3H, O-CH3), 4.71 (s, 2H, O-CH2), 6.92 (ddd, J = 27.7, 8.8, 2.5 Hz, 2H, ArH), 7.23–7.36 (m, 7H, ArH), 7.47 (dd, J = 11.3, 8.8 Hz, 2H, ArH), 8.22 (s, 2H, ArH), 12.33 (s, 2H, NH); 13C-NMR (101 MHz, DMSO-d6): δ (ppm) = 54.8 (CH3), 69.4 (CH2), 104.7, 106.2 (2C), 113.1, 113.4 (2C), 113.5, 127.5 (2C), 127.7, 128.4 (2C), 131.4, 131.7 (CH), 106.4 (2C) 125.7, 125.8, 131.8, 137.1, 153.6, 154.6, 176.3, 176.4, 194.7, 194.8 (C); C28H20N2O4 [448.48]; MS (EI): m/z (%) = 448 [M]+ (74), 392 [M+ − 56] (100); HRMS (EI) (m/z): Calcd. for [M]+∙= 448.14176, found [M]+ = 448.14204; isocratic HPLC: 98.4% at 254 nm and 99.1% at 280 nm, tms = 7.02 min, tm = 1.11 min (ACN/H2O 50:50); λmax (nm): 352, 277; gradient HPLC: 98.5% at 254 nm, tms = 12.2 min, tm = 1.25 min.