2.2. Synthesis of Compounds
2.2.1. N1,N6-Bis(3-(2-(1H-indol-3-yl)acetamido)propyl)hexane-1,6-diaminium 2,2,2-trifluoroacetate (14b)
Following general procedure A, indole-3-acetic acid (6) (0.050 g, 0.285 mmol) was reacted with EDC·HCl (0.065 g, 0.337 mmol), HOBt (0.046 g, 0.337 mmol), DIPEA (0.14 mL, 0.778 mmol) and di-tert-butyl hexane-1,6-diylbis((3-aminopropyl)carbamate) (13b) (0.056 g, 0.130 mmol) to afford di-tert-butyl hexane-1,6-diylbis((3-(2-(1H-indol-3-yl)acetamido)propyl)carbamate) (0.022 g, 23%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.011 g, 0.015 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 14b (0.011 g, 96%) as a white gum. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.63; IR (ATR) νmax 3262, 3059, 2932, 2857, 1668, 1619, 1541, 1471, 1435, 1330, 1198, 1178, 1129, 834, 799, 747, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.57 (2H, d, J = 7.8 Hz, H-4), 7.37 (2H, dt, J = 8.0, 1.0 Hz, H-7), 7.21 (2H, s, H-2), 7.11 (2H, td, J = 11.0, 0.9 Hz, H-6), 7.05 (2H, ddd, J = 15.3, 7.0, 0.9 Hz, H-5), 3.69 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.77 (4H, t, J = 7.0 Hz, H2-13), 2.70 (4H, t, J = 6.3 Hz, H2-15), 1.79 (4H, tt, J = 6.6, 6.6 Hz, H2-12), 1.53 (4H, tt, J = 3.6, 3.6 Hz, H2-16), 1.30–1.27 (4H, m, H2-17); 13C NMR (CD3OD, 100 MHz) δ 176.6 (C-9), 138.3 (C-7a), 128.4 (C-3a), 125.2 (C-2), 122.7 (C-6), 120.1 (C-5), 119.3 (C-4), 112.6 (C-7), 109.4 (C-3), 48.3 (C-15, obscured by solvent), 45.9 (C-13), 36.6 (C-11), 34.0 (C-8), 27.7 (C-12), 26.9 (C-17), 26.8 (C-16); (+)-HRESIMS [M + H]+ m/z 545.3596 (calcd for C32H45N6O2, 545.3599).
2.2.2. N1,N7-Bis(3-(2-(1H-indol-3-yl)acetamido)propyl)heptane-1,7-diaminium 2,2,2-trifluoroacetate (14c)
Following general procedure A, indole-3-acetic acid (6) (0.050 g, 0.285 mmol) was reacted with EDC·HCl (0.065 g, 0.337 mmol), HOBt (0.046 g, 0.337 mmol), DIPEA (0.14 mL, 0.778 mmol) and di-tert-butyl heptane-1,7-diylbis((3-aminopropyl)carbamate) (13c) (0.058 g, 0.130 mmol) to afford di-tert-butyl octane-1,8-diylbis((3-(2-(1H-indol-3-yl)acetamido)propyl)carbamate) (0.044 g, 45%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.022 g, 0.029 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 14c (0.018 g, 79%) as a brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.60; IR (ATR) νmax 3262, 3059, 2932, 2857, 1668, 1619, 1541, 1471, 1435, 1330, 1199, 1178, 1128, 835, 799, 747, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.57 (2H, d, J = 7.9 Hz, H-4), 7.37 (2H, dt, J = 8.3, 1.0 Hz, H-7), 7.21 (2H, s, H-2), 7.12 (2H, ddd, J = 15.3, 6.8, 0.9 Hz, H-6), 7.03 (2H, ddd, J = 15.0, 7.0, 0.9 Hz, H-5), 3.69 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.77 (4H, t, J = 7.1 Hz, H2-13), 2.73 (4H, t, J = 7.8 Hz, H2-15), 1.79 (4H, tt, J = 6.8, 6.5 Hz, H2-12), 1.58–1.52 (4H, m, H2-16), 1.34–1.29 (6H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 138.2 (C-7a), 128.4 (C-3a), 125.2 (C-2), 122.7 (C-6), 120.1 (C-5), 119.3 (C-4), 112.6 (C-7), 109.4 (C-3), 48.7 (C-15, obscured by solvent), 45.9 (C-13), 36.7 (C-11), 34.0 (C-8), 29.5 (C-18), 27.6 (C-12), 27.2 (C-17), 27.0 (C-16); (+)-HRESIMS [M + H]+ m/z 559.3755 (calcd for C33H47N6O2, 559.3755).
2.2.3. N1,N8-Bis(3-(2-(1H-indol-3-yl)acetamido)propyl)octane-1,8-diaminium 2,2,2-trifluoroacetate (14d)
Following general procedure A, indole-3-acetic acid (6) (0.050 g, 0.285 mmol) was reacted with EDC·HCl (0.065 g, 0.337 mmol), HOBt (0.046 g, 0.337 mmol), DIPEA (0.14 mL, 0.778 mmol) and di-tert-butyl octane-1,8-diylbis((3-aminopropyl)carbamate) (13d) (0.060 g, 0.130 mmol) to afford di-tert-butyl octane-1,8-diylbis((3-(2-(1H-indol-3-yl)acetamido)propyl)carbamate) (0.022 g, 22%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.011 g, 0.014 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 14d (0.10 g, 88%) as a brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.57; IR (ATR) νmax 3266, 3063, 2933, 2857, 1668, 1620, 1470, 1435, 1330, 1199, 1178, 1128, 835, 799, 747, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.57 (2H, d, J = 7.9 Hz, H-4), 7.37 (2H, dt, J = 7.8, 1.0 Hz, H-7), 7.21 (2H, s, H-2), 7.12 (2H, ddd, J = 8.2, 7.0, 1.1 Hz, H-6), 7.03 (2H, ddd, J = 7.8, 6.9, 0.8 Hz, H-5), 3.69 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.78 (4H, t, J = 7.1 Hz, H2-13), 2.73 (4H, t, J = 7.8 Hz, H2-15), 1.79 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.59–1.52 (4H, m, H2-16), 1.34–1.31 (8H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.4 (C-9), 138.2 (C-7a), 128.4 (C-3a), 125.2 (C-2), 122.7 (C-6), 120.1 (C-5), 119.3 (C-4), 112.6 (C-7), 109.4 (C-3), 48.5 (C-15, obscured by solvent), 46.0 (C-13), 36.7 (C-11), 34.0 (C-8), 29.8 (C-18), 27.6 (C-12), 27.3 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 573.3911 (calcd for C34H49N6O2, 573.3912).
2.2.4. N1,N10-Bis(3-(2-(1H-indol-3-yl)acetamido)propyl)decane-1,10-diaminium 2,2,2-trifluoroacetate (14e)
Following general procedure A, indole-3-acetic acid (6) (0.050 g, 0.285 mmol) was reacted with EDC·HCl (0.065 g, 0.337 mmol), HOBt (0.046 g, 0.337 mmol), DIPEA (0.14 mL, 0.778 mmol) and di-tert-butyl decane-1,10-diylbis((3-aminopropyl)carbamate) (13e) (0.063 g, 0.130 mmol) to yield di-tert-butyl decane-1,10-diylbis((3-(2-(1H-indol-3-yl)acetamido)propyl)carbamate) (0.082 g, 79%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.048 g, 0.060 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 14e (0.043 g, 86%) as a pink-brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.35; IR (ATR) νmax 3267, 3062, 2933, 2857, 1668, 1621, 1471, 1434, 1330, 1199, 1177, 1128, 834, 799, 748, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.57 (2H, d, J = 7.9 Hz, H-4), 7.37 (2H, d, J = 8.0 Hz, H-7), 7.21 (2H, s, H-2), 7.12 (2H, td, J = 7.5, 1.0 Hz, H-6), 7.03 (2H, ddd, J = 7.9, 7.1, 0.9 Hz, H-5), 3.68 (4H, s, H2-8), 3.28 (4H, t, J = 6.7 Hz, H2-11), 2.77 (4H, t, J = 7.5 Hz, H2-13), 2.71 (4H, t, J = 7.8 Hz, H2-15), 1.79 (4H, tt, J = 6.9, 6.9 Hz, H2-12), 1.54 (4H, tt, J = 7.5, 7.5 Hz, H2-16), 1.38–1.29 (12H, m, H2-17, H2-18 and H2-19); 13C NMR (CD3OD, 100 MHz) δ 176.4 (C-9), 138.2 (C-7a), 128.4 (C-3a), 125.2 (C-2), 122.7 (C-6), 120.0 (C-5), 119.3 (C-4), 112.6 (C-7), 109.4 (C-3), 48.9 (C-15), 46.0 (C-13), 36.7 (C-11), 34.0 (C-8), 30.3 (C-19), 30.1 (C-18), 27.6 (C-12), 27.4 (C-17), 27.1 (C-16); (+)-HRESIMS [M + H]+ m/z 601.4224 (calcd for C36H53N6O2, 601.4225).
2.2.5. N1,N12-Bis(3-(2-(1H-indol-3-yl)acetamido)propyl)dodecane-1,12-diaminium 2,2,2-trifluoroacetate (14f)
Following general procedure A, indole-3-acetic acid (6) (0.050 g, 0.285 mmol) was reacted with EDC·HCl (0.065 g, 0.337 mmol), HOBt (0.046 g, 0.337 mmol), DIPEA (0.14 mL, 0.778 mmol) and di-tert-butyl dodecane-1,12-diylbis((3-aminopropyl)carbamate) (13f) (0.067 g, 0.130 mmol) to afford di-tert-butyl dodecane-1,12-diylbis((3-(2-(1H-indol-3-yl)acetamido)propyl)carbamate) (0.050 g, 46%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.030 g, 0.036 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 14f (0.023 g, 74%) as a brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.30; IR (ATR) νmax 3267, 3064, 2927, 2854, 1668, 1621, 1538, 1471, 1435, 1333, 1199, 1178, 1128, 835, 799, 750, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.57 (2H, d, J = 7.8 Hz, H-4), 7.37 (2H, d, J = 8.3 Hz, H-7), 7.21 (2H, s, H-2), 7.12 (2H, td, J = 7.5, 1.0 Hz, H-6), 7.03 (2H, td, J = 7.5, 1.2 Hz, H-5), 3.68 (4H, s, H2-8), 3.28 (4H, t, J = 6.4 Hz, H2-11), 2.75 (4H, t, J = 7.2 Hz, H2-13), 2.69 (4H, t, J = 7.9 Hz, H2-15), 1.78 (4H, tt, J = 6.8, 6.8 Hz, H2-12), 1.53 (4H, tt, J = 7.4, 7.4 Hz, H2-16), 1.34–1.28 (16H, m, H2-17, H2-18, H2-19 and H2-20); 13C NMR (CD3OD, 100 MHz) δ 176.3 (C-9), 138.2 (C-7a), 128.4 (C-3a), 125.2 (C-2), 122.7 (C-6), 120.1 (C-5), 119.3 (C-4), 112.6 (C-7), 109.4 (C-3), 48.9 (C-15), 46.0 (C-13), 36.7 (C-11), 34.0 (C-8), 30.6 (C-20), 30.5 (C-19), 30.1 (C-18), 27.6 (C-12), 27.4 (C-17), 27.1 (C-16); (+)-HRESIMS [M + H]+ m/z 629.4537 (calcd for C38H57N6O2, 629.4538).
2.2.6. N1,N6-Bis(3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)hexane-1,6-diaminium 2,2,2-trifluoroacetate (15b)
Following general procedure A, 5-bromoindole-3-acetic acid (7) (0.050 g, 0.197 mmol) was reacted with EDC·HCl (0.045 g, 0.233 mmol), HOBt (0.031 g, 0.233 mmol), DIPEA (0.09 mL, 0.537 mmol) and di-tert-butyl hexane-1,6-diylbis((3-aminopropyl)carbamate) (13b) (0.039 g, 0.0894 mmol) to afford di-tert-butyl hexane-1,6-diylbis((3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)carbamate) (0.064 g, 79%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.028 g, 0.031 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 15b (0.027 g, 94%) as an orange oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.35; IR (ATR) νmax 3264, 2941, 2852, 1668, 1554, 1471, 1199, 1178, 1128, 884, 834, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.75 (2H, d, J = 1.8 Hz, H-4), 7.30 (2H, d, J = 8.2 Hz, H-7), 7.24 (2H, s, H-2), 7.21 (2H, dd, J = 8.6, 1.9 Hz, H-6), 3.66 (4H, s, H2-8), 3.31 (4H, obscured by solvent, H2-11), 2.82 (4H, t, J = 6.9 Hz, H2-13), 2.79 (4H, t, J = 7.6 Hz. H2-15), 1.82 (4H, tt, J = 6.7, 6.6 Hz, H2-12), 1.62–1.55 (4H, m, H2-16), 1.33 (4H, tt, J = 3.7, 3.7 Hz, H2-17); 13C NMR (CD3OD, 100 MHz) δ 176.0 (C-9), 136.8 (C-7a), 130.3 (C-3a), 126.7 (C-2), 125.4 (C-6), 122.1 (C-4), 114.3 (C-7), 113.2 (C-5), 109.4 (C-3), 49.1 (C-15), 46.0 (C-13), 36.7 (C-11), 33.8 (C-8), 29.6 (C-18), 27.7 (C-12), 26.94 (C-17), 26.88 (C-16); (+)-HRESIMS [M + H]+ m/z 701.1800 (calcd for C32H4379Br2N6O2, 701.1809), 703.1784 (calcd for C32H4379Br81BrN6O2, 703.1791), 705.1772 (calcd for C32H4381Br2N6O2, 705.1778).
2.2.7. N1,N7-Bis(3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)heptane-1,7-diaminium 2,2,2-trifluoroacetate (15c)
Following general procedure A, 5-bromoindole-3-acetic acid (7) (0.050 g, 0.197 mmol) was reacted with EDC·HCl (0.045 g, 0.233 mmol), HOBt (0.031 g, 0.233 mmol), DIPEA (0.09 mL, 0.537 mmol) and di-tert-butyl heptane-1,7-diylbis((3-aminopropyl)carbamate) (13c) (0.040 g, 0.0894 mmol) to afford di-tert-butyl heptane-1,7-diylbis((3-(2-(1H-indol-3-yl)acetamido)propyl)carbamate) (0.060 g, 73%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.031 g, 0.034 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 15c (0.030 g, 94%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.35; IR (ATR) νmax 2940, 2860, 1671, 1467, 1178, 1129, 884, 835, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.75 (2H, d, J = 1.9 Hz, H-4), 7.30 (2H, d, J = 8.8 Hz, H-7), 7.24 (2H, s, H-2), 7.21 (2H, dd, J = 8.6, 1.9 Hz, H-6), 3.65 (4H, s, H2-8), 3.31 (4H, obscured by solvent, H2-11), 2.82 (4H, t, J = 6.6 Hz, H2-13), 2.78 (4H, t, J = 7.5 Hz, H2-15), 1.81 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.58 (4H, tt, J = 7.7, 7.4 Hz, H2-16), 1.38–1.30 (6H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.0 (C-9), 136.8 (C-7a), 130.3 (C-3a), 126.7 (C-2), 125.4 (C-6), 122.1 (C-4), 114.3 (C-7), 113.2 (C-5), 109.4 (C-3), 49.1 (C-15), 46.0 (C-13), 36.7 (C-11), 33.8 (C-8), 29.6 (C-18), 27.7 (C-12), 27.2 (C-17), 27.1 (C-16); (+)-HRESIMS [M + H]+ m/z 715.1945 (calcd for C33H4579Br2N6O2, 715.1965), 717.1906 (calcd for C33H4579Br81BrN6O2, 717.1948), 719.1872 (calcd for C33H4581Br2N6O2, 719.1935).
2.2.8. N1,N8-Bis(3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)octane-1,8-diaminium 2,2,2-trifluoroacetate (15d)
Following general procedure A, 5-bromoindole-3-acetic acid (7) (0.050 g, 0.197 mmol) was reacted with EDC·HCl (0.045 g, 0.233 mmol), HOBt (0.031 g, 0.233 mmol), DIPEA (0.09 mL, 0.537 mmol) and di-tert-butyl octane-1,8-diylbis((3-aminopropyl)carbamate) (13d) (0.036 g, 0.089 mmol) to afford di-tert-butyl octane-1,8-diylbis((3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)carbamate) (0.052 g, 62%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.023 g, 0.025 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 15d (0.015 g, 63%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.33; IR (ATR) νmax 2939, 2858, 1671, 1467, 1199, 1178, 1128, 884, 834, 798, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.75 (2H, d, J = 1.8 Hz, H-4), 7.30 (2H, d, J = 8.3 Hz, H-7), 7.24 (2H, s, H-2), 7.21 (2H, dd, J = 7.2, 2.0 Hz, H-6), 3.65 (4H, s, H2-8), 3.33–3.28 (4H, obscured by solvent, H2-11), 2.84–2.76 (8H, m, H2-13 and H2-15), 1.81 (4H, tt, J = 6.7, 6.5 Hz, H2-12), 1.58 (4H, tt, J = 6.8, 6.7 Hz, H2-16), 1.39–1.31 (8H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.0 (C-9), 136.8 (C-7a), 130.2 (C-3a), 126.7 (C-2), 125.4 (C-6), 122.1 (C-4), 114.2 (C-7), 113.2 (C-5), 109.4 (C-3), 48.7 (C-15, obscured by solvent), 46.0 (C-13), 36.7 (C-11), 33.8 (C-8), 29.9 (C-18), 27.7 (C-12), 27.4 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 729.2135 (calcd for C34H4779Br2N6O2, 729.2122), 731.2149 (calcd for C34H4779Br81BrN6O2, 731.2104), 733.2109 (calcd for C34H4781Br2N6O2, 733.2092).
2.2.9. N1,N10-Bis(3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)decane-1,10-diaminium 2,2,2-trifluoroacetate (15e)
Following general procedure A, 5-bromoindole-3-acetic acid (7) (0.050 g, 0.197 mmol) was reacted with EDC·HCl (0.045 g, 0.233 mmol), HOBt (0.031 g, 0.233 mmol), DIPEA (0.09 mL, 0.537 mmol) and di-tert-butyl decane-1,10-diylbis((3-aminopropyl)carbamate) (13e) (0.044 g, 0.0894 mmol) to yield di-tert-butyl decane-1,10-diylbis((3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)carbamate) (0.019 g, 22%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.012 g, 0.013 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 15e (0.005 g, 40%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.28; IR (ATR) νmax 3280, 2928, 2855, 1671, 1556, 1457, 1376, 1289, 1199, 1177, 1130, 1044, 883, 834, 798, 749, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.75 (2H, d, J = 1.8 Hz, H-4), 7.30 (2H, d, J = 8.7 Hz, H-7), 7.24 (2H, s, H-2), 7.21 (2H, dd, J = 8.5, 1.9 Hz, H-6), 3.65 (4H, s, H2-8), 3.31–3.27 (4H, m, H2-11), 2.83–2.76 (8H, m, H2-13 and H2-15), 1.81 (4H, tt, J = 6.8, 6.8 Hz, H2-12), 1.59–1.56 (4H, m, H2-16), 1.38–1.30 (12H, m, H2-17, H2-18 and H2-19); 13C NMR (CD3OD, 100 MHz) δ 176.0 (C-9), 136.9 (C-7a), 130.2 (C-3a), 126.7 (C-2), 125.4 (C-6), 122.1 (C-4), 114.3 (C-7), 113.2 (C-5), 109.4 (C-3), 49.1 (C-15), 46.0 (C-13), 36.7 (C-11), 33.8 (C-8), 30.4 (C-19), 30.2 (C-18), 27.7 (C-12), 27.5 (C-17), 27.3 (C-16); (+)-HRESIMS [M + H]+ m/z 757.2427 (calcd for C36H5179Br2N6O2, 757.2435), 759.2409 (calcd for C36H5179Br81BrN6O2, 759.2418), 761.2390 (calcd for C36H5181Br2N6O2, 761.2406).
2.2.10. N1,N12-Bis(3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)dodecane-1,12-diaminium 2,2,2-trifluoroacetate (15f)
Following general procedure A, 5-bromoindole-3-acetic acid (7) (0.050 g, 0.197 mmol) was reacted with EDC·HCl (0.045 g, 0.233 mmol), HOBt (0.031 g, 0.233 mmol), DIPEA (0.09 mL, 0.537 mmol) and di-tert-butyl dodecane-1,12-diylbis((3-aminopropyl)carbamate) (13f) (0.046 g, 0.0894 mmol) to afford di-tert-butyl dodecane-1,12-diylbis((3-(2-(5-bromo-1H-indol-3-yl)acetamido)propyl)carbamate) (0.029 g, 33%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.022 g, 0.018 mmol) was treated with TFA/CH2Cl2. The crude product was purified with C8 reversed-phase flash column chromatography (50% MeOH/H2O (0.05% TFA)) affording the di-TFA salt 15f (0.018 g, 97%) as an orange oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.25; IR (ATR) νmax 3268, 2928, 2855, 1671, 1656, 1457, 1376, 1289, 1200, 1178, 1130, 1044, 883, 834, 798, 749, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.75 (2H, d, J = 1.8 Hz, H-4), 7.30 (2H, d, J = 8.4 Hz, H-7), 7.24 (2H, s, H-2), 7.21 (2H, dd, J = 8.6, 1.9 Hz, H-6), 3.65 (4H, s, H2-8), 3.31 (4H, obscured by solvent, H2-11), 2.83–2.76 (8H, m, H2-13 and H2-15), 1.80 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.57 (4H, tt, J = 7.0, 6.9 Hz, H2-16), 1.36–1.29 (16H, m, H2-17, H2-18, H2-19 and H2-20); 13C NMR (CD3OD, 100 MHz) δ 176.0 (C-9), 136.9 (C-7a), 130.2 (C-3a), 126.7 (C-2), 125.4 (C-6), 122.1 (C-4), 114.2 (C-7), 113.2 (C-5), 109.4 (C-3), 49.1 (C-15), 46.0 (C-13), 36.7 (C-11), 33.8 (C-8), 30.6 (C-20), 30.5 (C-19), 30.2 (C-18), 27.7 (C-12), 27.5 (C-17), 27.3 (C-16); (+)-HRESIMS [M + H]+ m/z 785.2732 (calcd for C38H5579Br2N6O2, 785.2748), 787.2702 (calcd for C38H5579Br81BrN6O2, 787.2731), 789.2703 (calcd for C38H5581Br2N6O2, 789.2720).
2.2.11. N1,N6-Bis(3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)hexane-1,6-diaminium 2,2,2-trifluoroacetate (16b)
Following general procedure A, 5-methoxyindole-3-acetic acid (8) (0.052 g, 0.256 mmol) was reacted with EDC·HCl (0.058 g, 0.302 mmol), HOBt (0.041 g, 0.302 mmol), DIPEA (0.12 mL, 0.69 mmol) and di-tert-butyl hexane-1,6-diylbis((3-aminopropyl)carbamate) (13b) (0.050 g, 0.116 mmol) to afford di-tert-butyl hexane-1,6-diylbis((3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.046 g, 51%) as a colorless oil. Following general procedure B, a sub-sample of this product (0.031 g, 0.039 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 16b (0.024 g, 75%) as a dark purple gum. Rf (RP-18, 10% aq HCl:MeOH 3:7) 0.65; IR (ATR) νmax 3289, 2944, 1675, 1488, 1202, 1134, 1059, 835, 800, 722 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.26 (2H, d, J = 8.9 Hz, H-7), 7.17 (2H, s, H-2), 7.08 (2H, d, J = 2.4 Hz, H-4), 6.79 (2H, dd, J = 8.8, 2.4 Hz, H-6), 3.81 (6H, s, OMe), 3.65 (4H, s, H2-8), 3.28 (4H, t, J = 6.8 Hz, H2-11), 2.78 (4H, t, J = 7.2 Hz, H2-13), 2.70 (4H, t, J = 7.8 Hz, H2-15), 1.80 (4H, tt, J = 7.2, 6.8 Hz, H2-12), 1.57–1.48 (4H, m, H2-16), 1.30–1.24 (4H, m, H2-17); 13C NMR (CD3OD, 100 MHz) δ 176.4 (C-9), 155.2 (C-5), 133.4 (C-7a), 128.8 (C-3a), 125.9 (C-2), 113.2 (C-7), 112.8 (C-6), 109.3 (C-3), 101.6 (C-4), 56.4 (OMe), 48.7 (C-15), 45.9 (C-13), 36.7 (C-11), 34.0 (C-8), 27.6 (C-12), 26.9 (C-16/C-17), 26.8 (C-16/C-17); (+)-HRESIMS [M + Na]+ m/z 627.3643 (calcd C34H48N6O4Na, 627.3629).
2.2.12. N1,N7-Bis(3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)heptane-1,7-diaminium 2,2,2-trifluoroacetate (16c)
Following general procedure A, 5-methoxyindole-3-acetic acid (8) (0.051 g, 0.248 mmol) was reacted with EDC·HCl (0.056 g, 0.293 mmol), HOBt (0.040 g, 0.293 mmol), DIPEA (0.12 mL, 0.677 mmol) and di-tert-butyl heptane-1,7-diylbis((3-aminopropyl)carbamate) (13c) (0.050 g, 0.113 mmol) to afford di-tert-butyl heptane-1,7-diylbis((3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.048 g, 52%) as a colorless oil. Following general procedure B, a sub-sample of this product (0.033 g, 0.040 mmol) was deprotected to afford the di-TFA salt 16c (0.033 g, 97%) as a dark purple gum. Rf (RP-18, 10% aq HCl:MeOH 3:7) 0.65; IR (ATR) νmax 3283, 2941, 1675, 1486, 1202,1180, 1134, 1059, 1027, 835, 800, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.26 (2H, d, J = 8.9 Hz, H-7), 7.17 (2H, s, H-2), 7.08 (2H, d, J = 2.4 Hz, H-4), 6.79 (2H, dd, J = 8.8, 2.4 Hz, H-6), 3.81 (6H, s, OMe), 3.65 (4H, s, H2-8), 3.29 (4H, t, J = 6.3 Hz, H2-11), 2.77 (4H, t, J = 7.2 Hz, H2-13), 2.70 (4H, t, J = 7.7 Hz, H2-15), 1.80 (4H, tt, J = 7.2, 6.3 Hz, H2-12), 1.58–1.49 (4H, m, H2-16), 1.32–1.26 (6H, m, H2-17, H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.4 (C-9), 155.2 (C-5), 133.4 (C-7a), 128.7 (C-3a), 125.9 (C-2), 113.2 (C-7), 112.8 (C-6), 109.2 (C-3), 101.6 (C-4), 56.4 (OMe), 49.0 (C-15), 46.0 (C-13), 36.7 (C-11), 34.1 (C-8), 29.4 (C-18), 27.6 (C-12), 27.1 (C-16/C-17), 27.0 (C-16/C-17); (+)-HRESIMS [M + H]+ m/z 619.3965 (calcd for C35H51N6O4, 619.3966).
2.2.13. N1,N8-Bis(3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)octane-1,8-diaminium 2,2,2-trifluoroacetate (16d)
Following general procedure A, 5-methoxyindole-3-acetic acid (8) (0.049 g, 0.239 mmol) was reacted with EDC·HCl (0.054 g, 0.283 mmol), HOBt (0.038 g, 0.283 mmol), DIPEA (0.11 mL, 0.654 mmol) and di-tert-butyl octane-1,8-diylbis((3-aminopropyl)carbamate) (13d) (0.050 g, 0.110 mmol), to afford di-tert-butyl octane-1,8-diylbis((3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate (0.069 g, 59%) as a colorless oil. Following general procedure B, a sub-sample of this product (0.054 g, 0.065 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 16d (0.054 g, 97%) as a dark purple gum. Rf (RP-18, 10% aq HCl:MeOH 3:7) 0.65; IR (ATR) νmax 3288, 2939, 2859, 1675, 1489, 1202, 1180, 1134, 1059, 1028, 834, 800, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.26 (2H, d, J = 8.9 Hz, H-7), 7.17 (2H, s, H-2), 7.07 (2H, d, J = 2.4 Hz, H-4), 6.79 (2H, dd, J = 8.8, 2.4 Hz, H-6), 3.80 (6H, s, OMe), 3.64 (4H, s, H2-8), 3.28 (4H, t, J = 6.4 Hz, H2-11), 2.76 (4H, t, J = 7.3 Hz, H2-13), 2.68 (4H, t, J = 7.8 Hz, H2-15), 1.79 (4H, tt, J = 7.3, 6.4 Hz, H2-12), 1.57–1.49 (4H, m, H2-16), 1.32–1.25 (8H, m, H2-17, H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.4 (C-9), 155.2 (C-5), 133.4 (C-7a), 128.7 (C-3a), 125.9 (C-2), 113.2 (C-7), 112.7 (C-6), 109.2 (C-3), 101.6 (C-4), 56.4 (OMe), 48.9 (C-15), 46.0 (C-13), 36.7 (C-11), 34.1 (C-8), 29.8 (C-18), 27.6 (C-12), 27.3 (C-16/C-17), 27.1 (C-16/C-17); (+)-HRESIMS [M + H]+ m/z 633.4125 (calcd for C36H53N6O4, 633.4123).
2.2.14. N1,N10-Bis(3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)decane-1,10-diaminium 2,2,2-trifluoroacetate (16e)
Following general procedure A, 5-methoxyindole-3-acetic acid (8) (0.050 g, 0.244 mmol) was reacted with EDC·HCl (0.055 g, 0.288 mmol), HOBt (0.039 g, 0.288 mmol), DIPEA (0.12 mL, 0.665 mmol) and di-tert-butyl decane-1,10-diylbis((3-aminopropyl)carbamate) (13e) (0.054 g, 0.111 mmol) to yield di-tert-butyl decane-1,10-diylbis((3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.045 g, 47%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.027 g, 0.031 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 16e (0.020 g, 72%) as a brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.50; IR (ATR) νmax 3283, 2935, 2857, 1672, 1488, 1440, 1303, 1201, 1181, 1134, 1059, 1027, 917, 836, 801, 722 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.26 (2H, d, J = 8.8 Hz, H-7), 7.18 (2H, s, H-2), 7.08 (2H, d, J = 2.4 Hz, H-4), 6.79 (2H, dd, J = 8.8, 2.4 Hz, H-6), 3.82 (6H, s, OMe), 3.64 (4H, s, H2-8), 3.29 (4H, t, J = 6.8 Hz, H2-11), 2.77 (4H, t, J = 7.2 Hz, H2-13), 2.70 (4H, t, J = 7.8 Hz, H2-15), 1.79 (4H, tt, J = 6.8, 6.8 Hz, H2-12), 1.57–1.51 (4H, m, H2-16), 1.38–1.28 (12H, m, H2-17, H2-18 and H2-19); 13C NMR (CD3OD, 100 MHz) δ 176.4 (C-9), 155.3 (C-5), 133.4 (C-7a), 128.7 (C-3a), 125.8 (C-2), 113.2 (C-7), 112.7 (C-6), 109.2 (C-3), 101.6 (C-4), 56.4 (OMe), 48.8 (C-15), 46.0 (C-13), 36.7 (C-11), 34.1 (C-8), 30.3 (C-19), 30.1 (C-18), 27.6 (C-12), 27.4 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 661.4433 (calcd for C38H57N6O4, 661.4436).
2.2.15. N1,N12-Bis(3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)dodecane-1,12-diaminium 2,2,2-trifluoroacetate (16f)
Following general procedure A, 5-methoxyindole-3-acetic acid (8) (0.050 g, 0.244 mmol) was reacted with EDC·HCl (0.055 g, 0.288 mmol), HOBt (0.039 g, 0.288 mmol), DIPEA (0.12 mL, 0.665 mmol) and di-tert-butyl dodecane-1,12-diylbis((3-aminopropyl)carbamate) (13f) (0.057 g, 0.111 mmol) to afford di-tert-butyl dodecane-1,12-diylbis((3-(2-(5-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.048 g, 49%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.040 g, 0.045 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 16f (0.007 g, 17%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.47; IR (ATR) νmax 3286, 2936, 2857, 1672, 1488, 1440, 1303, 1201, 1181, 1134, 1059, 1027, 918, 836, 801, 722 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.26 (2H, d, J = 8.8 Hz, H-7), 7.18 (2H, s, H-2), 7.08 (2H, d, J = 2.4 Hz, H-4), 6.79 (2H, dd, J = 8.8, 2.4 Hz, H-6), 3.82 (6H, s, OMe), 3.65 (4H, s, H2-8), 3.30–3.28 (4H, m, H2-11), 2.77 (4H, t, J = 7.2 Hz, H2-13), 2.70 (4H, t, J = 7.9 Hz, H2-15), 1.79 (4H, tt, J = 6.7, 6.7 Hz, H2-12), 1.57–1.50 (4H, m, H2-16), 1.38–1.28 (16H, m, H2-17, H2-18, H2-19 and H2-20); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 155.3 (C-5), 133.4 (C-7a), 128.7 (C-3a), 125.9 (C-2), 113.2 (C-7), 112.7 (C-6), 109.4 (C-3), 101.7 (C-4), 56.4 (OMe), 48.8 (C-15), 46.0 (C-13), 36.7 (C-11), 34.1 (C-8), 30.6 (C-20), 30.5 (C-19), 30.2 (C-18), 27.7 (C-12), 27.5 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 689.4744 (calcd for C40H61N6O4, 689.4749).
2.2.16. N1,N4-Bis(3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)butane-1,4-diaminium 2,2,2-trifluoroacetate (17a)
Following general procedure A, 5-methylindole-3-acetic acid (9) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl butane-1,4-diylbis((3-aminopropyl)carbamate) (13a) (0.048 g, 0.120 mmol) to afford di-tert-butyl butane-1,4-diylbis((3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.068 g, 76%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.010 g, 0.013 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 17a (0.009 g, 87%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.80; IR (ATR) νmax 3281, 3033, 2923, 2853, 1670, 1556, 1471, 1431, 1199, 1177, 1127, 834, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.34 (2H, s, H-4), 7.25 (2H, d, J = 8.4 Hz, H-7), 7.14 (2H, s, H-2), 6.96 (2H, dd, J = 8.2, 1.5 Hz, H-6), 3.67 (4H, s, H2-8), 3.31 (4H, obscured by solvent, H2-11), 2.81 (4H, t, J = 7.0 Hz, H2-13), 2.72 (4H, t, J = 6.6 Hz, H2-15), 2.41 (6H, s, Me), 1.81 (4H, tt, J = 6.6, 6.6 Hz, H2-12), 1.54 (4H, tt, J = 3.6, 3.6 Hz, H2-16); 13C NMR (CD3OD, 100 MHz) δ 176.7 (C-9), 136.5 (C-7a), 129.2 (C-5), 128.7 (C-3a), 125.3 (C-2), 124.4 (C-6), 118.9 (C-4), 112.3 (C-7), 108.8 (C-3), 47.9 (C-15), 45.9 (C-13), 36.6 (C-11), 33.9 (C-8), 27.7 (C-12), 24.0 (C-16), 21.7 (Me); (+)-HRESIMS [M + H]+ m/z 545.3600 (calcd for C32H45N6O2, 545.3599).
2.2.17. N1,N6-Bis(3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)hexane-1,6-diaminium 2,2,2-trifluoroacetate (17b)
Following general procedure A, 5-methylindole-3-acetic acid (9) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl hexane-1,6-diylbis((3-aminopropyl)carbamate) (13b) (0.052 g, 0.120 mmol) to yield di-tert-butyl hexane-1,6-diylbis((3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.068 g, 73%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.045 g, 0.085 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 17b (0.024 g, 51%) as a brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.73; IR (ATR) νmax 3282, 3033, 2923, 2853, 1670, 1556, 1470, 1432, 1199, 1178, 1127, 834, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.35 (2H, s, H-4), 7.25 (2H, d, J = 8.4 Hz, H-7), 7.15 (2H, s, H-2), 6.95 (2H, dd, J = 8.3, 1.4 Hz, H-6), 3.67 (4H, s, H2-8), 3.29 (4H, t, J = 6.4 Hz, H2-11), 2.79 (4H, t, J = 7.1 Hz, H2-13), 2.72 (4H, t, J = 7.8 Hz, H2-15), 2.41 (6H, s, Me), 1.80 (4H, tt, J = 6.7, 6.7 Hz, H2-12), 1.57–1.49 (4H, m, H2-16), 1.28 (4H, tt, J = 3.6, 3.6 Hz, H2-17); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 136.5 (C-7a), 129.2 (C-5), 128.6 (C-3a), 125.2 (C-2), 124.3 (C-6), 118.9 (C-4), 112.3 (C-7), 108.9 (C-3), 48.5 (C-15, obscured by solvent), 45.9 (C-13), 36.7 (C-11), 33.9 (C-8), 27.6 (C-12), 26.82 (C-17), 26.77 (C-16), 21.7 (Me); (+)-HRESIMS [M + H]+ m/z 573.3903 (calcd for C34H49N6O2, 573.3912).
2.2.18. N1,N7-Bis(3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)heptane-1,7-diaminium 2,2,2-trifluoroacetate (17c)
Following general procedure A, 5-methylindole-3-acetic acid (9) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl heptane-1,7-diylbis((3-aminopropyl)carbamate) (13c) (0.053 g, 0.120 mmol) to afford di-tert-butyl heptane-1,7-diylbis((3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.059 g, 62%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.039 g, 0.050 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 17c (0.038 g, 94%) as a dark brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.73; IR (ATR) νmax 3285, 3036, 2924, 2853, 1670, 1556, 1469, 1431, 1199, 1177, 1127, 834, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.38 (2H, s, H-4), 7.25 (2H, d, J = 8.3 Hz, H-7), 7.15 (2H, s, H-2), 6.95 (2H, dd, J = 8.3, 1.3 Hz, H-6), 3.65 (4H, s, H2-8), 3.28 (4H, t, J = 6.4 Hz, H2-11), 2.78 (4H, t, J = 7.2 Hz, H2-13), 2.71 (4H, t, J = 7.2 Hz, H2-15), 2.41 (6H, s, Me), 1.79 (4H, tt, J = 6.7, 6.7 Hz, H2-12), 1.57–1.50 (4H, m, H2-16), 1.34–1.27 (6H, m, H2-17); 13C NMR (CD3OD, 100 MHz) δ 176.4 (C-9), 136.5 (C-7a), 129.1 (C-5), 128.6 (C-3a), 125.2 (C-2), 124.3 (C-6), 118.9 (C-4), 112.3 (C-7), 108.9 (C-3), 48.7 (C-15, obscured by solvent), 45.9 (C-13), 36.7 (C-11), 34.0 (C-8), 29.5 (C-18), 27.5 (C-12), 27.1 (C-17), 27.0 (C-16), 21.7 (Me); (+)-HRESIMS [M + H]+ m/z 587.4076 (calcd for C35H51N6O2, 587.4068).
2.2.19. N1,N8-Bis(3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)octane-1,8-diaminium 2,2,2-trifluoroacetate (17d)
Following general procedure A, 5-methylindole-3-acetic acid (9) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl octane-1,8-diylbis((3-aminopropyl)carbamate) (13d) (0.55 g, 0.120 mmol) to yield di-tert-butyl octane-1,8-diylbis((3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.082 g, 85%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.041 g, 0.051 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 17d (0.007 g, 17%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.70; IR (ATR) νmax 3278, 2925, 2857, 1670, 1556, 1471, 1432, 1198, 1177, 1127, 834, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.35 (2H, s, H-4), 7.25 (2H, d, J = 8.3 Hz, H-7), 7.16 (2H, s, H-2), 6.96 (2H, dd, J = 8.3, 2.0 Hz, H-6), 3.66 (4H, s, H2-8), 3.29 (4H, t, J = 6.4 Hz, H2-11), 2.79 (4H, t, J = 7.1 Hz, H2-13), 2.72 (4H, t, J = 7.8 Hz, H2-15), 2.41 (6H, s, Me), 1.80 (4H, tt, J = 6.7, 6.5 Hz, H2-12), 1.58–1.51 (4H, m, H2-16), 1.37–1.30 (8H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.6 (C-9), 136.6 (C-7a), 129.2 (C-5), 128.6 (C-3a), 125.2 (C-2), 124.3 (C-6), 118.9 (C-4), 112.3 (C-7), 108.9 (C-3), 48.9 (C-15), 45.9 (C-13), 36.7 (C-11), 34.0 (C-8), 29.9 (C-19), 27.6 (C-12), 27.3 (C-18), 27.2 (C-17), 27.1 (C-16), 21.7 (Me); (+)-HRESIMS [M + H]+ m/z 601.4225 (calcd for C36H53N6O2, 601.4225).
2.2.20. N1,N10-Bis(3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)decane-1,10-diaminium 2,2,2-trifluoroacetate (17e)
Following general procedure A, 5-methylindole-3-acetic acid (9) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl decane-1,10-diylbis((3-aminopropyl)carbamate) (13e) (0.058 g, 0.120 mmol) to yield di-tert-butyl decane-1,10-diylbis((3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.042 g, 42%) as a yellow oil. Following general procedure B, a sub-sample of this product (0.018 g, 0.022 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 17e (0.014 g, 75%) as a pale yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.67; IR (ATR) νmax 3279, 2925, 2855, 1670, 1556, 1431, 1199, 1177, 1127, 834, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.36 (2H, s, H-4), 7.25 (2H, d, J = 8.2 Hz, H-7), 7.16 (2H, s, H-2), 6.95 (2H, dd, J = 8.2, 1.4 Hz, H-6), 3.65 (4H, s, H2-8), 3.29 (4H, t, J = 6.5 Hz, H2-11), 2.78 (4H, t, J = 6.9 Hz, H2-13), 2.71 (4H, t, J = 7.8 Hz, H2-15), 2.41 (6H, s, Me), 1.79 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.54 (4H, tt, J = 7.5, 7.5 Hz, H2-16), 1.38–1.26 (12H, m, H2-17, H2-18 and H2-19); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 136.6 (C-7a), 129.1 (C-5), 128.6 (C-3a), 125.2 (C-2), 124.3 (C-6), 118.9 (C-4), 112.3 (C-7), 108.9 (C-3), 48.7 (C-15, obscured by solvent), 45.9 (C-13), 36.7 (C-11), 34.0 (C-8), 30.3 (C-19), 30.1 (C-18), 27.6 (C-12), 27.5 (C-17), 27.2 (C-16), 21.7 (Me); (+)-HRESIMS [M + H]+ m/z 629.4537 (calcd for C38H57N6O2, 629.4538).
2.2.21. N1,N12-Bis(3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)dodecane-1,12-diaminium 2,2,2-trifluoroacetate (17f)
Following general procedure A, 5-methylindole-3-acetic acid (9) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl dodecane-1,12-diylbis((3-aminopropyl)carbamate) (13f) (0.062 g, 0.120 mmol) to afford di-tert-butyl dodecane-1,12-diylbis((3-(2-(5-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.082 g, 80%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.041 g, 0.048 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 17f (0.036 g, 85%) as a brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.60; IR (ATR) νmax 3282, 2925, 2855, 1670, 1655, 1471, 1431, 1199, 1177, 1127, 834, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.36 (2H, s, H-4), 7.23 (2H, d, J = 8.3 Hz, H-7), 7.16 (2H, s, H-2), 6.96 (2H, d, J = 8.3 Hz, H-6), 3.65 (4H, s, H2-8), 3.29 (4H, t, J = 6.6 Hz, H2-11), 2.78 (4H, t, J = 7.2 Hz, H2-13), 2.71 (4H, t, J = 7.9 Hz, H2-15), 2.41 (6H, s, Me), 1.79 (4H, tt, J = 6.7, 6.6 Hz, H2-12), 1.58–1.50 (4H, m, H2-16), 1.39–1.28 (16H, m, H2-17, H2-18, H2-19 and H2-20); 13C NMR (CD3OD, 100 MHz) δ 176.6 (C-9), 136.6 (C-7a), 129.1 (C-5), 128.6 (C-3a), 125.2 (C-2), 124.3 (C-6), 118.9 (C-4), 112.3 (C-7), 108.9 (C-3), 48.6 (C-15, obscured by solvent), 45.8 (C-13), 36.7 (C-11), 34.0 (C-8), 27.6 (C-12), 30.6 (C-20), 30.5 (C-19), 30.2 (C-18), 27.5 (C-17), 27.2 (C-16), 21.7 (Me); (+)-HRESIMS [M + H]+ m/z 657.4844 (calcd for C40H61N6O2, 657.4851).
2.2.22. N1,N4-Bis(3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)butane-1,4-diaminium 2,2,2-trifluoroacetate (18a)
Following general procedure A, 7-fluoroindole-3-acetic acid (10) (0.040 g, 0.207 mmol) was reacted with EDC·HCl (0.047 g, 0.245 mmol), HOBt (0.033 g, 0.245 mmol), DIPEA (0.10 mL, 0.565 mmol) and di-tert-butyl butane-1,4-diylbis((3-aminopropyl)carbamate) (13a) (0.038 g, 0.094 mmol) to afford di-tert-butyl butane-1,4-diylbis((3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)carbamate) (0.047 g, 66%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.020 g, 0.027 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 18a (0.019 g, 92%) as a red oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.83; IR (ATR) νmax 3263, 3081, 2829, 1669, 1643, 1581, 1433, 1365, 1199, 1179, 1127, 1048, 969, 835, 798, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.36 (2H, d, J = 7.9 Hz, H-4), 7.25 (2H, s, H-2), 6.98 (2H, td, J = 7.9, 4.7 Hz, H-5), 6.85 (2H, dd, J = 11.5, 7.4 Hz, H-6), 3.69 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.82 (4H, t, J = 7.1 Hz, H2-13), 2.78 (4H, t, J = 6.7 Hz, H2-15), 1.82 (4H, tt, J = 6.7, 6.7 Hz, H2-12), 1.59 (4H, tt, J = 3.8, 3.7 Hz, H2-16); 13C NMR (CD3OD, 100 MHz) δ 176.1 (C-9), 151.2 (d, 1JCF = 243.2 Hz, C-7), 132.5 (d, 3JCF = 5.8 Hz, C-3a), 126.2 (C-2), 126.1 (d, 2JCF = 15.8 Hz, C-7a), 120.4 (d, 3JCF = 6.2 Hz, C-5), 115.5 (d, 4JCF = 3.2 Hz, C-4), 110.5 (d, 4JCF = 1.7 Hz, C-3), 107.3 (d, 2JCF = 16.4 Hz, C-6), 48.0 (C-15), 46.1 (C-13), 36.8 (C-11), 33.8 (C-9), 27.7 (C-12), 24.1 (C-16); (+)-HRESIMS [M + H]+ m/z 553.3096 (calcd for C30H39F2N6O2, 553.3097).
2.2.23. N1,N6-Bis(3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)hexane-1,6-diaminium 2,2,2-trifluoroacetate (18b)
Following general procedure A, 7-fluoroindole-3-acetic acid (10) (0.040 g, 0.207 mmol) was reacted with EDC·HCl (0.047 g, 0.245 mmol), HOBt (0.033 g, 0.245 mmol), DIPEA (0.10 mL, 0.565 mmol) and di-tert-butyl hexane-1,6-diylbis((3-aminopropyl)carbamate) (13b) (0.041 g, 0.094 mmol) to afford di-tert-butyl hexane-1,6-diylbis((3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)carbamate) (0.048 g, 65%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.024 g, 0.031 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 18b (0.007 g, 28%) as a red-brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.67; IR (ATR) νmax 3266, 3082, 2829, 1669, 1643, 1581, 1436, 1365, 1198, 1179, 1127, 1048, 969, 835, 798, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.37 (2H, d, J = 8.0 Hz, H-4), 7.25 (2H, s, H-2), 6.98 (2H, td, J = 7.9, 4.7 Hz, H-5), 6.88–6.83 (2H, m, H-6), 3.69 (4H, s, H2-8), 3.31 (4H, obscured by solvent, H2-11), 2.82 (4H, t, J = 7.1 Hz, H2-13), 2.76 (4H, t, J = 7.8 Hz, H2-15), 1.81 (4H, tt, J = 6.7, 6.7 Hz, H2-12), 1.56–1.52 (4H, m, H2-16), 1.35–1.26 (4H, m, H2-17); 13C NMR (CD3OD, 100 MHz) δ 176.2 (C-9), 151.2 (d, 1JCF = 242.3 Hz, C-7), 132.5 (C-3a), 126.5 (C-2), 126.5 (C-2 and C-7a, obscured by solvent), 120.3 (d, 3JCF = 6.1 Hz, C-5), 115.4 (d, 4JCF = 3.1 Hz, C-4), 110.5 (C-3), 107.3 (d, 2JCF = 16.6 Hz, C-6), 48.7 (C-15), 46.0 (C-13), 36.7 (C-11), 33.8 (C-8), 27.7 (C-12), 26.9 (C-16 and C-17); (+)-HRESIMS [M + H]+ m/z 581.3409 (calcd for C32H43F2N6O2, 581.3410).
2.2.24. N1,N7-Bis(3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)heptane-1,7-diaminium 2,2,2-trifluoroacetate (18c)
Following general procedure A, 7-fluoroindole-3-acetic acid (10) (0.040 g, 0.207 mmol) was reacted with EDC·HCl (0.047 g, 0.245 mmol), HOBt (0.033 g, 0.245 mmol), DIPEA (0.10 mL, 0.565 mmol) and di-tert-butyl heptane-1,7-diylbis((3-aminopropyl)carbamate) (13c) (0.042 g, 0.094 mmol) to afford di-tert-butyl heptane-1,7-diylbis((3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)carbamate) (0.029 g, 39%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.015 g, 0.019 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 18c (0.008 g, 52%) as a red oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.62; IR (ATR) νmax 3264, 3083, 2831, 1669, 1644, 1581, 1433, 1365, 1198, 1180, 1126, 1048, 969, 835, 798, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.37 (2H, d, J = 7.9 Hz, H-4), 7.25 (2H, s, H-2), 6.98 (2H, td, J = 7.9, 4.8 Hz, H-5), 6.85 (2H, dd, J = 11.1, 7.8 Hz, H-6), 3.69 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.81 (4H, t, J = 7.1 Hz, H2-13), 2.77 (4H, t, J = 7.8 Hz, H2-15), 1.81 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.55 (4H, tt, J = 7.2, 7.2 Hz, H2-16), 1.35–1.28 (6H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.1 (C-9), 151.2 (d, 1JCF = 243.0 Hz, C-7), 132.5 (d, 3JCF = 5.8 Hz, C-3a), 126.2 (C-2), 126.1 (C-2 and C-7a, obscured by solvent), 120.3 (d, 3JCF = 6.2 Hz, C-5), 115.4 (d, 4JCF = 3.2 Hz, C-4), 110.5 (d, 4JCF = 1.9 Hz, C-3), 107.3 (d, 2JCF = 16.7 Hz, C-6), 48.0 (C-15, obscured by solvent), 46.0 (C-13), 36.7 (C-11), 33.8 (C-8), 29.5 (C-18), 27.7 (C-12), 27.2 (C-17), 27.0 (C-16); (+)-HRESIMS [M + H]+ m/z 595.3552 (calcd for C33H45F2N6O2, 595.3567).
2.2.25. N1,N8-Bis(3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)octane-1,8-diaminium 2,2,2-trifluoroacetate (18d)
Following general procedure A, 7-fluoroindole-3-acetic acid (10) (0.040 g, 0.207 mmol) was reacted with EDC·HCl (0.047 g, 0.245 mmol), HOBt (0.033 g, 0.245 mmol), DIPEA (0.10 mL, 0.565 mmol) and di-tert-butyl octane-1,8-diylbis((3-aminopropyl)carbamate) (13d) (0.043 g, 0.094 mmol) to afford di-tert-butyl octane-1,8-diylbis((3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)carbamate) (0.025 g, 33%) as a yellow oil. Following general procedure B, a sub-sample of this product (0.013 g, 0.016 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 18d (0.005 g, 37%) as a red oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.60; IR (ATR) νmax 3267, 3082, 2830, 1669, 1645, 1531, 1433, 1365, 1198, 1179, 1126, 1048, 969, 835, 798, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.37 (2H, d, J = 8.1 Hz, H-4), 7.25 (2H, s, H-2), 6.98 (2H, td, J = 7.9, 4.5 Hz, H-5), 6.85 (2H, dd, J = 11.2, 7.8 Hz, H-6), 3.69 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.81 (4H, t, J = 7.1 Hz, H2-13), 2.77 (4H, t, J = 7.8 Hz, H2-15), 1.81 (4H, tt, J = 6.7, 6.7 Hz, H2-12), 1.54 (4H, tt, J = 7.3, 7.3 Hz, H2-16), 1.35–1.29 (8H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.1 (C-9), 151.3 (d, 1JCF = 247.3 Hz, C-7), 132.4 (C-3a), 126.2 (C-2), 126.2 (C-2 and C-7a, obscured by solvent), 120.3 (d, 3JCF = 6.6 Hz, C-5), 115.5 (C-4), 110.5 (C-3), 107.3 (d, 2JCF = 16.1 Hz, C-6), 48.3 (C-15, obscured by solvent), 46.0 (C-13), 36.7 (C-11), 33.8 (C-8), 29.9 (C-18), 27.7 (C-12), 27.4 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 609.3671 (calcd for C34H47F2N6O2, 609.3723).
2.2.26. N1,N10-Bis(3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)decane-1,10-diaminium 2,2,2-trifluoroacetate (18e)
Following general procedure A, 7-fluoroindole-3-acetic acid (10) (0.040 g, 0.0207 mmol) was reacted with EDC·HCl (0.047 g, 0.245 mmol), HOBt (0.033 g, 0.245 mmol), DIPEA (0.10 mL, 0.565 mmol) and di-tert-butyl decane-1,10-diylbis((3-aminopropyl)carbamate) (13e) (0.046 g, 0.094 mmol) to afford di-tert-butyl decane-1,10-diylbis((3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)carbamate) (0.062 g, 79%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.031 g, 0.031 mmol) was reacted with TFA in CH2Cl2 to yield, after chromatography, the di-TFA salt 18e (0.016 g, 50%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.57; IR (ATR) νmax 3266, 3082, 2829, 1669, 1645, 1581, 1436, 1365, 1199, 1180, 1127, 1048, 969, 835, 798, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.37 (2H, d, J = 7.4 Hz, H-4), 7.26 (2H, s, H-2), 6.98 (2H, td, J = 7.9, 4.7 Hz, H-5), 6.85 (2H, dd, J = 11.5, 8.0 Hz, H-6), 3.69 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.80 (4H, t, J = 7.2 Hz, H2-13), 2.76 (4H, t, J = 7.8 Hz, H2-15), 1.80 (4H, tt, J = 6.8, 6.8 Hz, H2-12), 1.58–1.52 (4H, m, H2-16), 1.39–1.27 (12H, m, H2-17, H2-18 and H2-19); 13C NMR (CD3OD, 100 MHz) δ 176.0 (C-9), 151.2 (d, 1JCF = 243.3 Hz, C-7), 132.5 (C-3a), 126.2 (C-2), 126.1 (C-2 and C-7a, obscured by solvent), 120.3 (d, 3JCF = 6.0 Hz, C-5), 115.5 (d, 4JCF = 3.4 Hz, C-4), 110.5 (C-3), 107.2 (d, 2JCF = 16.5 Hz, C-6), 48.2 (C-15), 46.0 (C-13), 36.8 (C-11), 33.9 (C-8), 30.4 (C-19), 30.2 (C-18), 27.6 (C-12), 27.5 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 637.4040 (calcd for C36H51F2N6O2, 637.4036).
2.2.27. N1,N12-Bis(3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)dodecane-1,12-diaminium 2,2,2-trifluoroacetate (18f)
Following general procedure A, 7-fluoroindole-3-acetic acid (10) (0.040 g, 0.0207 mmol) was reacted with EDC·HCl (0.047 g, 0.245 mmol), HOBt (0.033 g, 0.245 mmol), DIPEA (0.10 mL, 0.565 mmol) and di-tert-butyl dodecane-1,12-diylbis((3-aminopropyl)carbamate) (13f) (0.048 g, 0.094 mmol) to afford di-tert-butyl dodecane-1,12-diylbis((3-(2-(7-fluoro-1H-indol-3-yl)acetamido)propyl)carbamate) (0.025 g, 31%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.009 g, 0.010 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 18f (0.001 g, 11%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.50; IR (ATR) νmax 2931, 2858, 1669, 1646, 1581, 1493, 1437, 1176, 1135, 1047, 969, 836, 798, 705, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.37 (2H, d, J = 8.0 Hz, H-4), 7.25 (2H, s, H-2), 6.97 (2H, td, J = 7.8, 4.7 Hz, H-5), 6.84 (2H, dd, J = 11.5, 8.0 Hz, H-6), 3.68 (4H, s, H2-8), 3.29 (4H, t, J = 6.8 Hz, H2-11), 2.80 (4H, t, J = 7.2 Hz, H2-13), 2.74 (4H, t, J = 7.8 Hz, H2-15), 1.81 (4H, tt, J = 6.7, 6.6 Hz, H2-12), 1.57–1.51 (4H, m, H2-16), 1.34–1.28 (16H, m, H2-17, H2-18, H2-19 and H2-20); 13C NMR (CD3OD, 100 MHz) δ 176.0 (C-9), 151.2 (d, 1JCF = 243.4 Hz, C-7), 132.4 (d, 3JCF = 5.7 Hz, C-3a), 126.2 (C-2), 126.1 (C-2 and C-7a, obscured by solvent), 120.3 (d, 3JCF = 6.1 Hz, C-5), 115.4 (d, 4JCF = 3.2 Hz, C-4), 110.5 (d, 4JCF = 2.3 Hz, C-3), 107.2 (d, 2JCF = 16.5 Hz, C-6), 48.8 (C-15, obscured by solvent), 46.0 (C-13), 36.8 (C-11), 33.9 (C-8), 30.6 (C-20), 30.4 (C-19), 30.1 (C-18), 27.6 (C-12), 27.4 (C-17), 27.1 (C-16); (+)-HRESIMS [M + H]+ m/z 665.4344 (calcd for C38H55F2N6O2, 665.4349).
2.2.28. N1,N4-Bis(3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)butane-1,4-diaminium 2,2,2-trifluoroacetate (19a)
Following general procedure A, 7-methoxyindole-3-acetic acid (11) (0.050 g, 0.244 mmol) was reacted with EDC·HCl (0.055 g, 0.288 mmol), HOBt (0.039 g, 0.288 mmol), DIPEA (0.12 mL, 0.665 mmol) and di-tert-butyl butane-1,4-diylbis((3-aminopropyl)carbamate) (13a) (0.045 g, 0.111 mmol) to afford di-tert-butyl butane-1,4-diylbis((3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.043 g, 50%) as a pale brown oil. Following general procedure B, a sub-sample of this product (0.011 g, 0.014 mmol) was reacted with TFA in CH2Cl2 to yield, after chromatography, the di-TFA salt 19a (0.009 g, 79%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.65; IR (ATR) νmax 2921, 1671, 1457, 1179, 1127, 834, 799, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.16 (2H, d, J = 7.9 Hz, H-4), 7.15 (2H, s, H-2), 6.97 (2H, dd, J = 7.9, 7.7 Hz, H-5), 6.65 (2H, d, J = 7.7 Hz, H-6), 3.93 (6H, s, OMe), 3.68 (4H, s, H2-8), 3.31 (4H, obscured by solvent, H2-11), 2.78 (4H, t, J = 6.9 Hz, H2-13), 2.69 (4H, t, J = 7.3 Hz, H2-15), 1.80 (4H, tt, J = 6.6, 6.5 Hz, H2-12), 1.52 (4H, tt, J = 3.6, 3.6 Hz, H2-16); 13C NMR (CD3OD, 100 MHz) δ 176.7 (C-9), 148.0 (C-7), 129.9 (C-3a), 128.4 (C-7a), 124.8 (C-2), 120.8 (C-5), 112.2 (C-4), 109.8 (C-3), 102.8 (C-6), 55.8 (OMe), 47.8 (C-15), 45.8 (C-13), 36.5 (C-11), 34.0 (C-8), 27.7 (C-12), 23.9 (C-16); (+)-HRESIMS [M + H]+ m/z 577.3500 (calcd for C32H45N6O4, 577.3497).
2.2.29. N1,N6-Bis(3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)hexane-1,6-diaminium 2,2,2-trifluoroacetate (19b)
Following general procedure A, 7-methoxyindole-3-acetic acid (11) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.055 g, 0.288 mmol), HOBt (0.039 g, 0.288 mmol), DIPEA (0.12 mL, 0.665 mmol) and di-tert-butyl hexane-1,6-diylbis((3-aminopropyl)carbamate) (13b) (0.045 g, 0.111 mmol) to afford di-tert-butyl hexane-1,6-diylbis((3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.037 g, 41%) as a clear colorless oil. Following general procedure B, a sub-sample of the protected products (0.007 g, 0.009 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 19b (0.005 g, 69%) as a brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.60; IR (ATR) νmax 2922, 1671, 1457, 1178, 1127, 834, 799, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.16 (2H, d, J = 7.9 Hz, H-4), 7.15 (2H, s, H-2), 6.97 (2H, dd, J = 7.9, 7.6 Hz, H-5), 6.65 (2H, d, J = 7.6 Hz, H-6), 3.93 (6H, s, OMe), 3.67 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.78 (4H, t, J = 7.0 Hz, H2-13), 2.72 (4H, t, J = 7.3 Hz, H2-15), 1.80 (4H, tt, J = 6.7, 6.6 Hz, H2-12), 1.52 (4H, tt, J = 7.5, 7.4 Hz, H2-16), 1.29–1.27 (4H, m, H2-17); 13C NMR (CD3OD, 100 MHz) δ 176.6 (C-9), 148.0 (C-7), 129.9 (C-3a), 128.4 (C-7a), 124.7 (C-2), 120.7 (C-5), 112.2 (C-4), 109.8 (C-3), 102.8 (C-6), 55.8 (OMe), 48.5 (C-15, obscured by solvent), 45.9 (C-13), 36.6 (C-11), 34.1 (C-8), 27.6 (C-12), 26.83 (C-17), 26.78 (C-16); (+)-HRESIMS [M + H]+ m/z 605.3810 (calcd for C34H43N6O4, 605.3810).
2.2.30. N1,N7-Bis(3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)heptane-1,7-diaminium 2,2,2-trifluoroacetate (19c)
Following general procedure A, 7-methoxyindole-3-acetic acid (11) (0.050 g, 0.244 mmol) was reacted with EDC·HCl (0.055 g, 0.288 mmol), HOBt (0.039 g, 0.288 mmol), DIPEA (0.12 mL, 0.665 mmol) and di-tert-butyl heptane-1,7-diylbis((3-aminopropyl)carbamate) (13c) (0.049 g, 0.111 mmol) to afford di-tert-butyl heptane-1,7-diylbis((3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.040 g, 44%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.021 g, 0.026 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 19c (0.008 g, 37%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.57; IR (ATR) νmax 2922, 1671, 1457, 1179, 1127, 834, 799, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.16 (2H, d, J = 7.6 Hz, H-4), 7.15 (2H, s, H-2), 6.96 (2H, dd, J = 7.7, 7.6 Hz, H-5), 6.65 (2H, d, J = 7.7 Hz, H-6), 3.93 (6H, s, OMe), 3.66 (4H, s, H2-8), 3.29 (4H, t, J = 6.5 Hz, H2-11), 2.77 (4H, t, J = 7.1 Hz, H2-13), 2.72 (4H, t, J = 7.8 Hz, H2-15), 1.80 (4H, tt, J = 6.6, 6.4 Hz, H2-12), 1.53 (4H, tt, J = 7.6, 7.5 Hz, H2-16), 1.33–1.28 (6H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 148.0 (C-7), 129.8 (C-3a), 128.4 (C-7a), 124.7 (C-2), 120.7 (C-5), 112.2 (C-4), 109.8 (C-3), 102.7 (C-6), 55.8 (OMe), 48.4 (C-15, obscured by solvent), 45.9 (C-13), 36.6 (C-11), 34.1 (C-8), 29.5 (C-18), 27.6 (C-12), 27.1 (C-17), 27.0 (C-16); (+)-HRESIMS [M + H]+ m/z 619.3946 (calcd for C35H51N6O4, 619.3966).
2.2.31. N1,N8-Bis(3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)octane-1,8-diaminium 2,2,2-trifluoroacetate (19d)
Following general procedure A, 7-methoxyindole-3-acetic acid (11) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.055 g, 0.288 mmol), HOBt (0.039 g, 0.288 mmol), DIPEA (0.12 mL, 0.665 mmol) and di-tert-butyl octane-1,8-diylbis((3-aminopropyl)carbamate) (13d) (0.051 g, 0.111 mmol) to afford di-tert-butyl octane-1,8-diylbis((3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.043 g, 47%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.021 g, 0.025 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 19d (0.011 g, 51%) as a yellow-brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.55; IR (ATR) νmax 2922, 1671, 1457, 1178, 1128, 835, 799, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.17 (2H, d, J = 7.8 Hz, H-4), 7.16 (2H, d, J = 1.2 Hz, H-2), 6.96 (2H, dd, J = 7.8, 7.7 Hz, H-5), 6.65 (2H, d, J = 7.7 Hz, H-6), 3.94 (6H, s, OMe), 3.67 (4H, s, H2-8), 3.29 (4H, obscured by solvent, H2-11), 2.77 (4H, t, J = 7.1 Hz, H2-13), 2.72 (4H, t, J = 7.8 Hz, H2-15), 1.79 (4H, tt, J = 6.7, 6.6 Hz, H2-12), 1.58–1.51 (4H, m, H2-16), 1.35–1.29 (8H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.6 (C-9), 148.1 (C-7), 129.8 (C-3a), 128.5 (C-7a), 124.7 (C-2), 120.7 (C-5), 112.2 (C-4), 109.8 (C-3), 102.8 (C-6), 55.8 (OMe), 48.3 (C-15, obscured by solvent), 45.9 (C-13), 36.6 (C-11), 34.1 (C-8), 29.9 (C-18), 27.7 (C-12), 27.3 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 633.4111 (calcd for C36H53N6O4, 633.4123).
2.2.32. N1,N10-Bis(3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)decane-1,10-diaminium 2,2,2-trifluoroacetate (19e)
Following general procedure A, 7-methoxyindole-3-acetic acid (11) (0.050 g, 0.244 mmol) was reacted with EDC·HCl (0.055 g, 0.288 mmol), HOBt (0.039 g, 0.288 mmol), DIPEA (0.12 mL, 0.665 mmol) and di-tert-butyl decane-1,10-diylbis((3-aminopropyl)carbamate) (13e) (0.054 g, 0.111 mmol) to yield di-tert-butyl decane-1,10-diylbis((3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.031 g, 33%) as a clear brown oil. Following general procedure B, a sub-sample of this product (0.015 g, 0.017 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 19e (0.009 g, 58%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.50; IR (ATR) νmax 3366, 3290, 3053, 2932, 2857, 1668, 1579, 1502, 1433, 1376, 1261, 1202, 1178, 1128, 1092, 1052, 941, 840, 797, 773, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.17 (2H, d, J = 7.9 Hz, H-4), 7.16 (2H, d, J = 0.8 Hz, H-2), 6.96 (2H, dd, J = 7.9, 7.5 Hz, H-5), 6.65 (2H, d, J = 7.5 Hz, H-6), 3.94 (6H, s, OMe), 3.66 (4H, s, H2-8), 3.29 (4H, obscured by solvent, H2-11), 2.76 (4H, t, J = 7.2 Hz, H2-13), 2.71 (4H, t, J = 7.8 Hz, H2-15), 1.78 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.54 (4H, tt, J = 7.5, 7.5 Hz, H2-16), 1.36–1.29 (12H, m, H2-17, H2-18 and H2-19); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 148.0 (C-7), 129.8 (C-3a), 128.5 (C-7a), 124.7 (C-2), 120.7 (C-5), 112.2 (C-4), 109.8 (C-3), 102.7 (C-6), 55.8 (OMe), 48.9 (C-15, obscured by solvent), 45.9 (C-13), 36.7 (C-11), 34.1 (C-8), 30.4 (C-19), 30.2 (C-18), 27.6 (C-12), 27.5 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 661.4433 (calcd for C38H57N6O4, 661.4436).
2.2.33. N1,N12-Bis(3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)dodecane-1,12-diaminium 2,2,2-trifluoroacetate (19f)
Following general procedure A, 7-methoxyindole-3-acetic acid (11) (0.050 g, 0.244 mmol) was reacted with EDC·HCl (0.055 g, 0.288 mmol), HOBt (0.039 g, 0.288 mmol), DIPEA (0.12 mL, 0.665 mmol) and di-tert-butyl dodecane-1,12-diylbis((3-aminopropyl)carbamate) (13f) (0.057 g, 0.111 mmol) to afford di-tert-butyl dodecane-1,12-diylbis((3-(2-(7-methoxy-1H-indol-3-yl)acetamido)propyl)carbamate) (0.029 g, 29%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.007 g, 0.008 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 19f (0.001 g, 14%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.47; IR (ATR) νmax 3367, 3290, 3051, 2932, 2857, 1668, 1579, 1502, 1434, 1375, 1261, 1202, 1178, 1128, 1092, 1052, 941, 840, 797, 774, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.17 (2H, d, J = 7.8 Hz, H-4), 7.16 (2H, d, J = 0.8 Hz, H-2), 6.96 (2H, dd, J = 7.8, 7.6 Hz, H-5), 6.65 (2H, d, J = 7.6 Hz, H-6), 3.94 (6H, s, OMe), 3.66 (4H, s, H2-8), 3.29 (4H, obscured by solvent, H2-11), 2.76 (4H, t, J = 7.1 Hz, H2-13), 2.70 (4H, t, J = 7.9 Hz, H2-15), 1.77 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.56–1.50 (4H, m, H2-16), 1.38–1.28 (16H, m, H2-17, H2-18, H2-19 and H2-20); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 148.0 (C-7), 129.8 (C-3a), 128.5 (C-7a), 124.7 (C-2), 120.7 (C-5), 112.2 (C-4), 109.8 (C-3), 102.7 (C-6), 55.8 (OMe), 48.8 (C-15, obscured by solvent), 45.9 (C-13), 36.6 (C-11), 34.1 (C-8), 30.7 (C-20), 30.6 (C-19), 30.2 (C-18), 27.6 (C-12), 27.5 (C-17), 27.2 (C-16); (+)-HRESIMS [M + H]+ m/z 689.4747 (calcd for C40H61N6O4, 689.4749).
2.2.34. N1,N4-Bis(3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)butane-1,4-diaminium 2,2,2-trifluoroacetate (20a)
Following general procedure A, 7-methylindole-3-acetic acid (12) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl butane-1,4-diylbis((3-aminopropyl)carbamate) (13a) (0.048 g, 0.120 mmol) to afford di-tert-butyl butane-1,4-diylbis((3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.015 g, 17%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.013 g, 0.018 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 20a (0.012 g, 89%) as a purple oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.55; IR (ATR) νmax 3288, 2834, 1669, 1542, 1435, 1340, 1199, 1183, 1130, 836, 800, 747, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.39 (2H, dd, J = 7.4, 0.9 Hz, H-4), 7.20 (2H, s, H-2), 6.95 (2H, t, J = 7.3 Hz, H-5), 6.92 (2H, d, J = 6.4 Hz, H-6), 3.69 (4H, s, H2-8), 3.30 (4H, obscured by solvent, H2-11), 2.78 (4H, t, J = 6.9 Hz, H2-13), 2.72 (4H, t, J = 7.8 Hz, H2-15), 2.47 (6H, s, Me), 1.80 (4H, tt, J = 6.6, 6.5 Hz, H2-12), 1.56 (4H, tt, J = 3.6, 3.6 Hz, H2-16); 13C NMR (CD3OD, 100 MHz) δ 176.7 (C-9), 137.6 (C-7a), 128.1 (C-3a), 125.1 (C-2), 123.2 (C-6), 122.2 (C-7), 120.4 (C-5), 117.0 (C-4), 109.7 (C-3), 47.9 (C15), 45.9 (C-13), 36.6 (C-11), 34.1 (C-8), 27.7 (C-12), 24.0 (C-16), 16.9 (Me); (+)-HRESIMS [M + Na]+ m/z 567.3417 (calcd for C32H44N6NaO2, 567.3418).
2.2.35. N1,N6-Bis(3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)hexane-1,6-diaminium 2,2,2-trifluoroacetate (20b)
Following general procedure A, 7-methylindole-3-acetic acid (12) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl hexane-1,6-diylbis((3-aminopropyl)carbamate) (13b) (0.052 g, 0.120 mmol) to yield di-tert-butyl hexane-1,6-diylbis((3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.058 g, 62%) as a pale yellow oil. Following general procedure B, a sub-sample of this product (0.029 g, 0.038 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 20b (0.016 g, 53%) as a yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.48; IR (ATR) νmax 3289, 3065, 2833, 1669, 1542, 1436, 1340, 1199, 1181, 1129, 835, 799, 748, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.40 (2H, d, J = 7.3 Hz, H-4), 7.20 (2H, s, H-2), 6.97–6.91 (4H, m, H-5 and H-6), 3.68 (4H, s, H2-8), 3.29 (4H, obscured by solvent, H2-11), 2.77 (4H, t, J = 7.0 Hz, H2-13), 2.71 (4H, t, J = 7.6 Hz, H2-15), 2.47 (6H, s, Me), 1.79 (4H, tt, J = 6.5, 6.3 Hz, H2-12), 1.57–1.50 (4H, m, H2-16), 1.31–1.26 (4H, m, H2-17); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 137.6 (C-7a), 128.0 (C-3a), 125.0 (C-2), 123.2 (C-6), 122.1 (C-7), 120.3 (C-5), 117.0 (C-4), 109.7 (C-3), 48.5 (C-15, obscured by solvent), 45.9 (C-13), 36.7 (C-11), 34.1 (C-8), 27.6 (C-12), 26.82 (C-17), 26.77 (C-16), 16.9 (Me); (+)-HRESIMS [M + H]+ m/z 573.3901 (calcd for C34H49N6O2, 573.3912).
2.2.36. N1,N7-Bis(3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)heptane-1,7-diaminium 2,2,2-trifluoroacetate (20c)
Following general procedure A, 7-methylindole-3-acetic acid (12) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl heptane-1,7-diylbis((3-aminopropyl)carbamate) (13c) (0.053 g, 0.120 mmol) to afford di-tert-butyl heptane-1,7-diylbis((3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.027 g, 29%) as a clear colorless oil. Following general procedure B, this product (0.027 g, 0.034 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 20c (0.021 g, 75%) as a clear colorless oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.40; IR (ATR) νmax 3279, 2939, 2859, 1671, 1554, 1436, 1344, 1199, 1178, 1128, 834, 799, 747, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.40 (2H, dd, J = 7.4, 1.1 Hz, H-4), 7.21 (2H, s, H-2), 6.95 (2H, t, J = 7.3 Hz, H-5), 6.92 (2H, d, J = 6.5 Hz, H-6), 3.68 (4H, s, H2-8), 3.28 (4H, t, J = 6.4 Hz, H2-11), 2.76 (4H, t, J = 7.1 Hz, H2-13), 2.70 (4H, t, J = 7.7 Hz, H2-15), 2.48 (6H, s, Me), 1.78 (4H, tt, J = 6.9, 6.8 Hz, H2-12), 1.54 (4H, tt, J = 7.6, 7.4 Hz, H2-16), 1.33–1.27 (6H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.4 (C-9), 137.6 (C-7a), 128.0 (C-3a), 125.0 (C-2), 123.2 (C-6), 122.1 (C-7), 120.3 (C-5), 117.0 (C-4), 109.8 (C-3), 49.8 (C15), 45.9 (C-13), 36.7 (C-11), 34.1 (C-8), 29.5 (C-18), 27.6 (C-12), 27.1 (C-17), 27.0 (C-16), 16.9 (Me); (+)-HRESIMS [M + H]+ m/z 587.4065 (calcd for C35H51N6O2, 587.4068).
2.2.37. N1,N8-Bis(3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)octane-1,8-diaminium 2,2,2-trifluoroacetate (20d)
Following general procedure A, 7-methylindole-3-acetic acid (12) (0.050 g, 0.264 mmol) was reacted with EDC·HCl (0.060 g, 0.312 mmol), HOBt (0.042 g, 0.312 mmol), DIPEA (0.13 mL, 0.721 mmol) and di-tert-butyl octane-1,8-diylbis((3-aminopropyl)carbamate) (13d) (0.55 g, 0.120 mmol) to yield di-tert-butyl octane-1,8-diylbis((3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.052, 54%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.020 g, 0.025 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 20d (0.014 g, 68%) as a pale yellow oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.38; IR (ATR) νmax 3280, 3057, 2940, 2860, 1670, 1555, 1436, 1344, 1199, 1178, 1128, 834, 799, 747, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.40 (2H, d, J = 7.3 Hz, H-4), 7.21 (2H, s, H-2), 6.97–6.91 (4H, m, H-5 and H-6), 3.68 (4H, s, H2-8), 3.28 (4H, obscured by solvent, H2-11), 2.76 (4H, t, J = 7.0 Hz, H2-13), 2.71 (4H, t, J = 7.8 Hz, H2-15), 2.48 (6H, s, Me), 1.78 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.54 (4H, tt, J = 7.4, 7.2 Hz, H2-16), 1.35–1.28 (8H, m, H2-17 and H2-18); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 137.6 (C-7a), 128.0 (C-3a), 125.0 (C-2), 123.2 (C-6), 122.1 (C-7), 120.3 (C-5), 117.0 (C-4), 109.7 (C-3), 48.4 (C-15, obscured by solvent), 45.9 (C-13), 36.6 (C-11), 34.2 (C-8), 29.9 (C-18), 27.6 (C-12), 27.3 (C-17), 27.1 (C-16), 16.9 (Me); (+)-HRESIMS [M + H]+ m/z 601.4224 (calcd for C36H53N6O2, 601.4225).
2.2.38. N1,N10-Bis(3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)decane-1,10-diaminium 2,2,2-trifluoroacetate (20e)
Following general procedure A, 7-methylindole-3-acetic acid (12) (0.025 g, 0.132 mmol) was reacted with EDC·HCl (0.030 g, 0.156 mmol), HOBt (0.021 g, 0.156 mmol), DIPEA (0.07 mL, 0.311 mmol) and di-tert-butyl decane-1,10-diylbis((3-aminopropyl)carbamate) (13e) (0.029 g, 0.060 mmol) to yield di-tert-butyl decane-1,10-diylbis((3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.037 g, 74%) as a clear colorless oil. Following general procedure B, a sub-sample of this product (0.014 g, 0.017 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 20e (0.010 g, 69%) as a pale brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.37; IR (ATR) νmax 3280, 3053, 2940, 1670, 1542, 1436, 1344, 1199, 1179, 1128, 834, 799, 747, 720 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.41 (2H, dd, J = 7.5, 1.1 Hz, H-4), 7.21 (2H, s, H-2), 6.97–6.91 (4H, m, H-5 and H-6), 3.68 (4H, s, H2-8), 3.29 (4H, obscured by solvent, H2-11), 2.76 (4H, t, J = 7.2 Hz, H2-13), 2.70 (4H, t, J = 7.9 Hz, H2-15), 2.48 (6H, s, Me), 1.78 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.54 (4H, tt, J = 7.1, 7.1 Hz, H2-16), 1.35–1.29 (12H, m, H2-17, H2-18 and H2-19); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 137.6 (C-7a), 128.0 (C-3a), 125.0 (C-2), 123.2 (C-6), 122.1 (C-7), 120.3 (C-5), 117.0 (C-4), 109.8 (C-3), 48.9 (C-15), 45.9 (C-13), 36.7 (C-11), 34.2 (C-8), 30.4 (C-19), 30.2 (C-18), 27.6 (C-12), 27.5 (C-17), 27.2 (C-16), 16.9 (Me); (+)-HRESIMS [M + H]+ m/z 629.4531 (calcd for C38H57N6O2, 629.4538).
2.2.39. N1,N12-Bis(3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)dodecane-1,12-diaminium 2,2,2-trifluoroacetate (20f)
Following general procedure A, 7-methylindole-3-acetic acid (12) (0.025 g, 0.132 mmol) was reacted with EDC·HCl (0.030 g, 0.156 mmol), HOBt (0.021 g, 0.156 mmol), DIPEA (0.07 mL, 0.311 mmol) and di-tert-butyl dodecane-1,12-diylbis((3-aminopropyl)carbamate) (13f) (0.031 g, 0.060 mmol) to afford di-tert-butyl dodecane-1,12-diylbis((3-(2-(7-methyl-1H-indol-3-yl)acetamido)propyl)carbamate) (0.035 g, 68%) as a clear oil. Following general procedure B, a sub-sample of this product (0.025 g, 0.029 mmol) was reacted with TFA in CH2Cl2 to afford, after chromatography, the di-TFA salt 20f (0.011 g, 43%) as a brown oil. Rf (RP-18, 10% aq HCl:MeOH 1:3) 0.33; IR (ATR) νmax 3275, 2938, 2860, 1670, 1542, 1436, 1344, 1199, 1179, 1129, 834, 799, 747, 721 cm−1; 1H NMR (CD3OD, 400 MHz) δ 7.41 (2H, dd, J = 7.1, 1.2 Hz, H-4), 7.21 (2H, s, H-2), 6.95 (2H, t, J = 7.3 Hz, H-5), 6.92 (2H, d, J = 6.4 Hz, H-6), 3.68 (4H, s, H2-8), 3.29 (4H, obscured by solvent, H2-11), 2.75 (4H, t, J = 7.2 Hz, H2-13), 2.69 (4H, t, J = 7.8 Hz, H2-15), 2.48 (6H, s, Me), 1.77 (4H, tt, J = 6.8, 6.7 Hz, H2-12), 1.52 (4H, tt, J = 7.8, 7.0 Hz, H2-16), 1.38–1.28 (16H, m, H2-17, H2-18, H2-19 and H2-20); 13C NMR (CD3OD, 100 MHz) δ 176.5 (C-9), 137.7 (C-7a), 128.0 (C-3a), 125.1 (C-2), 123.2 (C-6), 122.1 (C-7), 120.3 (C-5), 117.0 (C-4), 109.8 (C-3), 48.5 (C-15, obscured by solvent), 45.9 (C-13), 36.6 (C-11), 34.2 (C-8), 30.7 (C-20), 30.6 (C-19), 30.2 (C-18), 27.6 (C-12), 27.5 (C-17), 27.2 (C-16), 16.9 (Me); (+)-HRESIMS [M + H]+ m/z 657.4846 (calcd for C40H61N6O2, 657.4851).