3.2.4. Synthesis of Chimonanthus praecox Derivatives a1–a20 and b1–b19
5-methylnicotinic acid (0.2 g, 1.3 mmol, 2 eq) and dichloro sulfoxide (0.3 mL, 4.3 mmol) were dissolved in 10 mL of dichloromethane (DCM). The resulting mixture was heated to reflux for 2 h. The solvent was then removed under vacuum, and the acyl chloride was obtained. A combination of 3a, 8-Bis(3-(trifluoromethyl)benzyl)-1, 2, 3, 3a, 8, 8a-hexahydrop-yrrole [2, 3-b]indole (0.3 g, 0.6 mmol, 1 eq) and triethylamine (0.2 mL, 1.1 mmol) was dissolved in 10 mL of dichloromethane (DCM). The prepared acyl chloride in 10 mL of DME was slowly added. The mixture was stirred at r.m. and monitored by TLC. When the reaction was complete, the solvent was removed under reduced pressure. The residue was washed with water and saturated brine. The organic layer was dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography to produce the target product a5 (0.2 g), which was yellow and oily (Yield 64.0%). For the procedure for the remaining Chimonanthus praecox derivatives, refer to the steps of compound a5.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrole[2,3-b]indol-1(2H)-yl)(2-fluoropyridin-3-yl)methanone(a1): White solid, Melting Point: 131–133 °C, 90% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.28 (d, J = 4.7 Hz, 1H), 7.85 (t, J = 8.3 Hz, 1H), 7.42–7.33 (m, 1H), 7.01 (dd, J = 15.9, 7.5 Hz, 8H), 6.87 (t, J = 8.0 Hz, 2H), 6.69 (dt, J = 14.7, 7.5 Hz, 1H), 6.15 (d, J = 7.9 Hz, 1H), 5.99 (s, 1H), 4.58 (d, J = 16.3 Hz, 1H), 4.49 (d, J = 16.3 Hz, 1H), 3.43–3.35 (m, 1H), 3.30–3.20 (m, 1H), 3.14 (d, J = 13.4 Hz, 1H), 2.96 (d, J = 13.4 Hz, 1H), 2.30–2.22 (m, 8H).13C NMR (100 MHz, Acetone-d6) δ 164.43, 160.65, 158.29, 151.44, 149.70 (CH, d, J = 13.0 Hz ), 149.55, 141.06, 136.98, 136.45, 136.38, 135.21, 132.56, 130.66, 129.51, 129.25, 129.00, 127.51, 123.99, 122.70, 122.65, 120.49 (d, J = 32.4 Hz ), 120.16, 117.97, 106.87, 83.17, 57.69, 49.98, 48.39, 44.69, 38.36, 21.00, 20.95. MS(ESI(+)) calcd for C32H30FN3O+ [M + H]+: 492.24; found: 492.24.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(6-methylpyridin-3-yl)methanone(a2): White solid, Melting Point: 153–155 °C, 89% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.48 (s, 1H), 7.76–7.54 (m, 1H), 7.23 (d, J = 8.0 Hz, 1H), 6.99 (dq, J = 8.9, 7.4 Hz, 9H), 6.85 (d, J = 7.8 Hz, 2H), 6.64 (t, J = 7.3 Hz, 1H), 6.18–6.03 (m, 2H), 4.57 (d, J = 8.9 Hz, 1H), 4.43 (d, J = 8.9 Hz, 1H), 3.36 (d, J = 9.0 Hz, 1H), 3.10 (d, J = 13.3 Hz, 1H), 2.94 (d, J = 13.3 Hz, 1H), 2.48 (s, 3H), 2.28 (s, 3H), 2.24–2.20 (m, 5H).13C NMR (100 MHz, Acetone-d6) δ 168.43, 160.77, 151.45, 148.66, 137.13, 136.38, 136.33, 136.00, 135.28, 135.23, 132.68, 130.69, 130.06, 129.47, 129.21, 128.95, 127.43, 123.99, 122.88, 117.76, 106.74, 83.08, 57.27, 49.75, 49.68, 44.68, 38.49, 24.28, 20.98, 20.92. MS(ESI(+)) calcd for C33H33N3O+ [M + H]+: 488.27; found: 488.27.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(5,6-dichloropyridin-3-yl)methanone(a3): White solid, Melting Point: 130–132 °C, 91%, 1H NMR (400 MHz, Acetone-d6), δ: 8.28 (d, J = 48.1 Hz, 1H), 7.92 (s, 1H), 7.25–6.58 (m, 10H), 6.35–5.54 (m, 2H), 4.76–4.08 (m, 2H), 3.10–3.01 (m, 71.2, 43.9 Hz, 5H), 2.28 (d, J = 14.9 Hz, 8H).13C NMR (100 MHz, Acetone) δ 165.73, 151.43, 150.02, 147.00, 138.67, 137.26, 136.55, 136.45, 135.25, 133.70, 132.62, 130.74, 130.31, 130.29, 129.77, 129.55, 129.31, 129.08, 127.51, 124.06, 117.92, 106.76, 83.36, 57.39, 49.53, 44.61, 38.56, 32.15, 23.14, 20.98, 20.94. MS(ESI(+)) calcd for C32H29Cl2N3O+ [M + H]+: 542.18; found: 542.18.
(2-aminopyridin-3-yl)(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)methanone (a4): White solid, Melting Point: 164–166 °C, 88% Yield, 1H NMR (400 MHz, Chloroform-d), δ: 7.95 (s, 1H), 7.25 (s, 1H), 6.90 (t, J = 9.8 Hz, 11H), 6.52 (d, J = 9.8 Hz, 2H), 6.10 (s, 2H), 4.34 (s, 2H), 2.97 (d, J = 6.5 Hz, 2H), 2.15 (d, J = 4.2 Hz, 10H), 1.21 (s, 1H).13C NMR (100 MHz, Chloroform-d) δ 169.00, 157.53, 150.74, 150.20, 137.13, 137.01, 136.21, 136.14, 136.04, 133.97, 131.54, 130.09, 129.03, 128.83, 128.68, 126.76, 123.49, 117.30, 113.09, 112.39, 106.28, 82.50, 56.62, 49.25, 44.43, 37.86, 21.17, 21.14. MS(ESI(+)) calcd for C32H32N4O+ [M + H]+: 489.26; found: 489.26.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(5-methylpyridin-3-yl)methanone (a5): White solid, Melting Point: 93–95 °C, 64% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.45 (d, J = 6.4 Hz, 2H), 7.59 (s, 1H), 7.13–6.88 (m, 10H), 6.69 (t, J = 7.3 Hz, 1H), 6.20 (d, J = 7.8 Hz, 1H), 6.11 (s, 1H), 4.64 (d, J = 6.3 Hz, 1H), 4.48 (d, J = 6.3 Hz, 1H), 3.63–3.52 (m, 1H), 3.39 (dd, J = 8.4, 9.5 Hz, 1H), 3.15 (d, J = 13.3 Hz, 1H), 2.99 (d, J = 13.3 Hz, 1H), 2.37–2.25 (m, 11H).13C NMR (100 MHz, Acetone-d6) δ 167.70, 151.32, 150.78, 145.57, 136.50, 135.72, 135.66, 135.05, 134.61, 132.71, 132.02, 131.82, 130.02, 128.81, 128.56, 128.29, 126.77, 123.31, 117.10, 106.03, 82.39, 70.34, 56.60, 48.98, 43.93, 37.78, 31.44, 22.43, 20.28, 17.26, 13.51. MS(ESI(+)) calcd for C33H33N3O+ [M+H]+: 488.27; found: 488.27.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(6-chloropyridin-2-yl)methanone (a6): White solid, Melting Point: 130–132 °C, 83% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 7.94 (t, J = 7.8 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.56–7.49 (m, 1H), 7.08–6.97 (m, 8H), 6.84 (s, 1H), 6.66 (t, J = 7.3 Hz, 1H), 6.14 (d, J = 7.8 Hz, 1H), 6.00 (s, 1H), 4.62 (d, J = 6.2 Hz, 1H), 4.49 (d, J = 6.2 Hz, 1H), 3.82–3.75 (m, 1H), 3.43 (d, J = 6.3 Hz, 1H), 3.09–2.88 (m, 3H), 2.26–2.12 (m, 8H).13C NMR (100 MHz, Acetone-d6) δ 165.65, 154.57, 150.61, 149.22, 140.30, 136.37, 135.77, 135.67, 134.55, 132.22, 130.20, 130.08, 128.84, 128.70, 128.63, 128.57, 128.26, 126.98, 125.70, 125.66, 123.24, 122.80, 117.25, 106.34, 82.75, 59.34, 56.36, 49.33, 48.68, 43.81, 37.32, 20.28. MS(ESI(+)) calcd for C32H30ClN3O+ [M + H]+: 508.22; found: 508.22.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(naphthalen-1-yl)methanone (a7): White solid, Melting Point: 147–149 °C, 95% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 7.93 (d, J = 8.3 Hz, 2H), 7.63–7.34 (m, 4H), 7.26 (d, J = 6.4 Hz, 1H), 7.10 (s, 7H), 7.00 (dd, J = 10.9, 7.9 Hz, 3H), 6.66 (t, J = 7.4 Hz, 1H), 6.30–6.20 (m, 2H), 4.73 (d, J = 6.3 Hz, 2H), 3.18–2.97 (m, 4H), 2.34 (d, J = 7.1 Hz, 6H), 2.18 (d, J = 6.9 Hz, 2H).13C NMR (100 MHz, Acetone-d6) δ 169.57, 151.58, 151.55, 137.35, 136.56, 136.46, 136.05, 135.30, 134.16, 133.14, 131.02, 130.95, 130.01, 129.65, 129.61, 129.39, 129.03, 129.01, 127.65, 127.54, 127.01, 125.87, 125.51, 124.54, 123.99, 117.88, 106.61, 100.70, 57.70, 50.04, 48.49, 44.51, 38.38, 21.03, 20.97. MS(ESI(+)) calcd for C37H34N2O+ [M + H]+: 523.27; found: 523.27.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(2-chloropyridin-4-yl)methanone (a8): Light yellow solid, Melting Point: 107–109 °C, 90% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.41 (dd, J = 4.9, 0.6 Hz, 1H), 7.30–7.25 (m, 2H), 7.01–6.92 (m, 9H), 6.86 (d, J = 8.0 Hz, 1H), 6.65 (td, J = 7.4, 0.8 Hz, 1H), 6.19 (d, J = 7.8 Hz, 1H), 6.00 (s, 1H), 4.51 (d, J = 6.4 Hz, 2H), 3.43 (d, J = 1.9 Hz, 1H), 3.29–3.15 (m, 1H), 3.11 (d, J = 13.4 Hz, 1H), 2.95 (d, J = 13.4 Hz, 1H), 2.29 (s, 2H), 2.28–2.18 (m, 6H).13C NMR (100 MHz, Acetone-d6) δ 166.69, 151.87, 151.34, 150.86, 148.04, 137.20, 136.52, 136.41, 135.19, 132.60, 130.68, 129.51, 129.27, 129.03, 127.46, 123.99, 122.64, 121.23, 117.91, 106.73, 83.40, 57.39, 49.71, 49.27, 44.53, 38.52, 20.99, 20.95. MS(ESI(+)) calcd for C32H30ClN3O+ [M + H]+: 508.22; found: 508.22.
2-(3a,8-bis(4-methylbenzyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-1-carbonyl)benzaldehyde (a9): White solid, Melting Point: 97–99 °C, 92% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 7.58–7.49 (m, 4H), 7.08–6.97 (m, 7H), 6.73–6.54 (m, 4H), 6.21 (d, J = 7.8 Hz, 1H), 5.99 (s, 1H), 5.39 (s, 1H), 4.39 (d, J = 6.6 Hz, 3H), 3.57 (d, J = 9.5 Hz, 1H), 3.08–2.81 (m, 2H), 2.50–2.17 (m, 8H).13C NMR (100 MHz, Acetone-d6) δ 169.56, 151.55, 137.35, 136.56, 136.46, 136.05, 135.30, 134.16, 133.14, 130.95, 130.01, 129.65, 129.61, 129.39, 129.03, 129.01, 127.65, 127.54, 127.01, 125.87, 125.51, 124.54, 123.99, 117.88, 106.61, 57.70, 50.04, 48.49, 44.51, 38.38, 21.03, 20.97. MS(ESI(+)) calcd for C34H32N2O2 + [M + H]+: 501.25; found: 501.25.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(6-chloropyridin-3-yl)methanone (a10): White solid, Melting Point: 117–119 °C, 94% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.45 (d, J = 1.5 Hz, 1H), 7.88 (dd, J = 8.2, 1.9 Hz, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.09–6.87 (m, 10H), 6.69 (t, J = 7.3 Hz, 1H), 6.20 (d, J = 7.8 Hz, 1H), 6.09 (s, 1H), 4.62 (d, J = 16.3 Hz, 1H), 4.48 (d, J = 16.3 Hz, 1H), 3.60 (dd, J = 7.8, 4.5 Hz, 1H), 3.42 (dd, J = 18.4, 9.5 Hz, 1H), 3.15 (d, J = 13.2 Hz, 1H), 2.98 (d, J = 13.3 Hz, 1H), 2.30 (t, J = 11.0 Hz, 8H).13C NMR (100 MHz, Acetone-d6) δ 167.25, 152.95, 151.57, 149.61, 139.29, 137.27, 136.61, 136.52, 135.38, 132.77, 132.38, 130.85, 129.66, 129.40, 129.16, 127.59, 124.63, 124.17, 118.01, 106.92, 83.34, 71.19, 57.47, 49.81, 44.75, 38.56, 21.12, 21.05. MS(ESI(+)) calcd for C32H30ClN3O+ [M + H]+: 508.22; found: 508.22.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(pyridin-2-yl)methanone (a11): Light yellow solid, Melting Point: 120–122 °C, 90% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.55–8.45 (m, 1H), 7.92–7.86 (m, 1H), 7.73–7.68 (m, 1H), 7.49–7.41 (m, 1H), 7.06–6.96 (m, 7H), 6.87 (t, J = 8.5 Hz, 3H), 6.65 (dd, J = 7.4, 6.7 Hz, 1H), 6.16 (d, J = 7.8 Hz, 1H), 6.04 (s, 1H), 4.65 (d, J = 16.2 Hz, 1H), 4.50 (d, J = 16.2 Hz, 1H), 3.83 (ddd, J = 11.5, 6.1, 2.1 Hz, 1H), 3.42 (td, J = 11.3, 6.8 Hz, 1H), 3.09 (dd, J = 10.9, 5.7 Hz, 1H), 2.94 (dd, J = 13.5, 2.3 Hz, 1H), 2.30 (s, 3H), 2.26 (s, 3H), 2.22 (d, J = 3.0 Hz, 2H).13C NMR (100 MHz, Acetone-d6) δ 167.91, 155.13, 151.42, 148.67, 137.50, 137.15, 136.40, 136.30, 135.31, 133.00, 130.88, 130.75, 129.49, 129.32, 129.23, 128.87, 127.67, 126.76, 125.59, 125.32, 124.51, 123.89, 117.80, 106.92, 83.40, 57.04, 50.04, 49.30, 44.63, 38.26, 20.99, 20.94. MS(ESI(+)) calcd for C32H31N3O+ [M + H]+: 474.25; found: 474.25.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(4-methoxyphenyl)methanone (a12): Light yellow solid, Melting Point: 119–121 °C, 91% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 7.42 (s, 2H), 7.08–6.84 (m, 13H), 6.64 (t, J = 7.3 Hz, 1H), 6.14 (d, J = 7.7 Hz, 1H), 4.50 (dd, J = 80.9, 15.2 Hz, 2H), 3.82 (s, 3H), 3.69–3.23 (m, 2H), 3.10 (d, J = 13.3 Hz, 1H), 2.94 (d, J = 13.3 Hz, 1H), 2.28 (d, J = 16.9 Hz, 6H), 2.22–2.15 (m, 2H).13C NMR (100 MHz, Acetone-d6) δ 170.04, 161.91, 151.57, 137.14, 136.35, 136.29, 135.37, 132.90, 132.83, 132.80, 132.70, 130.74, 130.30, 129.46, 129.32, 129.22, 128.90, 127.48, 127.16, 123.98, 117.69, 113.90, 106.73, 83.02, 57.18, 55.54, 50.07, 49.59, 44.76, 38.51, 21.00, 20.94. MS(ESI(+)) calcd for C34H34N2O2+ [M + H]+: 503.27; found: 503.27.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(3-chloropyridin-4-yl)methanone (a13): White solid, Melting Point: 119–121 °C, 93% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.61 (s, 1H), 8.54 (d, J = 4.7 Hz, 1H), 7.11–6.88 (m, 11H), 6.69–6.62 (m, 1H), 6.18 (d, J = 7.6 Hz, 1H), 5.98 (s, 1H), 4.64 (d, J = 16.3 Hz, 1H), 4.51 (d, J = 16.3 Hz, 1H), 3.25–3.07 (m, 3H), 2.98 (d, J = 13.4 Hz, 1H), 2.29 (d, J = 9.1 Hz, 7H), 2.22–2.17 (m, 1H).13C NMR (100 MHz, Acetone-d6) δ 165.05, 151.39, 150.21, 149.17, 144.35, 136.99, 136.53, 136.45, 135.14, 132.65, 130.76, 129.60, 129.54, 129.32, 129.22, 129.04, 127.83, 127.60, 123.99, 122.49, 118.04, 106.78, 82.92, 57.87, 49.92, 47.87, 44.48, 38.58, 20.98. MS(ESI(+)) calcd for C32H30ClN3O+ [M + H]+: 508.22; found: 508.22.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(2-hydroxypyridin-3-yl)methanone (a14): Yellow oily, 83% Yield, 1H NMR (400 MHz, DMSO-d6), δ: 11.92 (d, J = 4.6 Hz, 1H), 7.46–7.35 (m, 2H), 7.06 (d, J = 7.1 Hz, 1H), 6.99–6.96 (m, 3H), 6.93–6.76 (m, 6H), 6.61 (d, J = 7.2 Hz, 1H), 6.26–6.16 (m, 1H), 6.02 (d, J = 7.8 Hz, 1H), 5.80 (s, 1H), 4.42 (d, J = 8.4 Hz, 2H), 3.07 (d, J = 13.4 Hz, 2H), 2.86 (d, J = 13.3 Hz, 1H), 2.25–2.20 (m, 7H), 2.10 (dd, J = 6.7, 2.5 Hz, 2H).13C NMR (100 MHz, DMSO-d6).δ 166.17, 158.73, 150.08, 140.48, 137.30, 135.77, 135.05, 134.26, 131.62, 131.21, 129.63, 129.55, 128.54, 128.36, 128.29, 128.16, 127.94, 126.50, 125.81, 123.58, 123.06, 116.61, 105.43, 104.50, 82.35, 81.42, 58.18, 56.33, 48.49, 46.81, 43.44, 20.57. MS(ESI(+)) calcd for C32H31N3O2+ [M + H]+: 490.25; found: 490.25.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(pyridin-4-yl)methanone (a15): Yellow oily, 92% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.62 (dd, J = 4.4, 1.5 Hz, 2H), 7.30 (dd, J = 4.4, 1.6 Hz, 2H), 7.09–6.96 (m, 9H), 6.87 (d, J = 8.0 Hz,2H), 6.66 (t, J = 7.3 Hz, 1H), 6.18 (d, J = 7.8 Hz, 1H), 6.03 (s, 1H), 4.60 (d, J = 16.3 Hz, 1H), 4.47 (d, J = 16.3 Hz, 1H), 3.35–3.27 (m, 1H), 3.12 (d, J = 13.3 Hz, 1H), 2.96 (d, J = 13.4 Hz, 1H), 2.30 (s, 3H), 2.26 (s, 3H), 2.24–2.19 (m, 2H).13C NMR (100 MHz, Acetone-d6) δ 168.03, 151.19, 150.47, 144.29, 136.92, 136.25, 136.16, 135.01, 132.44, 130.77, 130.48, 129.31, 129.04, 128.79, 127.27, 126.78, 123.79, 122.25, 121.86, 117.67, 106.60, 83.01, 57.18, 49.58, 49.22, 44.41, 38.20, 20.80, 20.73. MS(ESI(+)) calcd for C32H31N3O + [M + H]+: 474.25; found: 474.25.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(2-chloropyridin-3-yl)methanone (a16): Light yellow solid, Melting Point: 118–120 °C, 90% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.42 (dd, J = 4.7, 1.8 Hz, 1H), 7.46–7.39 (m, 1H), 7.31–6.92 (m, 10H), 6.90 (d, J = 8.0 Hz, 2H), 6.66 (t, J = 7.4 Hz, 1H), 6.18 (d, J = 6.4 Hz, 1H), 6.01 (s, 1H), 4.68 (d, J = 16.3 Hz, 1H), 4.53 (d, J = 16.3 Hz, 1H), 3.25 (dd, J = 9.8, 7.6 Hz, 1H), 3.16 (d, J = 13.3 Hz, 1H), 2.98 (d, J = 13.4 Hz, 1H), 2.31 (s, 3H), 2.29 (s, 3H), 2.26–2.15 (m, 2H).13C NMR (100 MHz, Acetone-d6)δ 165.56, 151.20, 150.58, 150.52, 146.77, 137.48, 136.81, 136.23, 136.16, 134.93, 133.57, 132.42, 130.52, 129.29, 129.07, 128.78, 127.35, 123.74), 123.53, 117.73, 106.48, 82.66, 57.63, 49.62, 47.77, 44.30, 38.36, 20.80, 20.76. MS(ESI(+)) calcd for C32H30ClN3O+ [M + H]+: 508.22; found: 508.22.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(5-methylpyrazin-2-yl)methanone (a17): Light yellow solid, Melting Point: 117–119 °C, 89% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.75 (d, J = 1.3 Hz, 1H), 8.45 (d, J = 0.8 Hz, 1H), 7.08–6.93 (m, 10H), 6.67–6.63 (m, 1H), 6.17 (d, J = 7.8 Hz, 1H), 4.62 (d, J = 16.1 Hz, 1H), 4.50 (d, J = 16.1 Hz, 1H), 3.47–3.37 (m, 1H), 3.08 (d, J = 13.4 Hz, 1H), 2.55 (s, 2H), 2.46 (s, 1H), 2.30–2.21 (m, 11H).13C NMR (100 MHz, Acetone-d6 ) δ 166.31, 155.96, 151.31, 147.20, 145.06, 142.71, 137.07, 136.45, 136.34, 135.22, 132.94, 130.89, 130.75, 129.49, 129.36, 129.24, 129.02, 128.92, 127.65, 126.34, 123.90, 117.91, 107.00, 83.48, 57.00, 50.10, 49.23, 44.53, 38.12, 21.48, 20.98, 20.94. MS(ESI(+)) calcd for C32H32N4O+ [M + H]+: 489.26; found: 489.26.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(pyridin-3-yl)methanone (a18): Light yellow solid, Melting Point: 92–94 °C, 93% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.62–8.59 (m, 2H), 7.77 (d, J = 7.8 Hz, 1H), 7.37 (dd, J = 7.7, 4.9 Hz, 1H), 7.24–6.90 (m, 10H), 6.87 (d, J = 7.8 Hz, 2H), 6.66 (t, J = 7.4 Hz, 1H), 6.18 (d, J = 7.8 Hz, 1H), 6.09 (s, 1H), 4.61 (d, J = 16.3 Hz, 1H), 4.47 (d, J = 16.3 Hz, 1H), 3.12 (d, J = 13.3 Hz, 1H), 2.98–2.89 (m, 1H), 2.30 (s, 3H), 2.26 (s, 3H), 2.24–2.20 (m, 2H).13C NMR (100 MHz, Acetone-d6)δ 168.17, 151.57, 151.40, 149.11, 137.10, 136.37, 136.30, 135.50, 135.22, 132.91, 132.62, 130.66, 129.47, 129.21, 128.96, 127.43, 123.98, 123.65, 117.78, 106.74, 83.15, 57.27, 49.68, 44.64, 38.47, 20.99, 20.93. MS(ESI(+)) calcd for C32H31N3O+ [M + H]+: 474.25; found: 474.25.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(5-chloropyrazin-2-yl)methanone (a19): Light yellow solid, Melting Point: 131–133 °C, 84% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.69 (d, J = 1.3 Hz, 1H), 8.66 (d, J = 1.3 Hz, 1H), 7.08 (dd, J = 7.3, 0.8 Hz, 1H), 7.01 (dt, J = 7.9, 4.6 Hz, 8H), 6.95 (dd, J = 10.0, 4.6 Hz, 1H), 6.85 (d, J = 7.9 Hz, 2H), 6.31–6.18 (m, 2H), 6.01 (s, 1H), 4.61 (d, J = 16.1 Hz, 1H), 4.50 (d, J = 16.2 Hz, 1H), 3.88–3.76 (m, 1H), 3.46–3.38 (m, 1H), 3.07–3.00 (m, 1H), 2.94 (d, J = 13.4 Hz, 1H), 2.29 (s, 3H), 2.26 (s, 3H).13C NMR (100 MHz, Acetone-d6) δ 165.16, 151.24, 150.35, 148.45, 145.69, 143.05, 137.00, 136.53, 136.39, 135.15, 132.88, 130.76, 129.52, 129.27, 128.98, 127.65, 126.16, 123.92, 118.04, 107.07, 83.52, 57.10, 50.12, 49.23, 44.45, 37.97, 20.97, 20.93. MS(ESI(+)) calcd for C31H29ClN4O+ [M + H]+: 509.21; found: 509.21.
(3a,8-bis(4-methylbenzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(pyrazin-2-yl)methanone (a20): White solid, Melting Point: 105–107 °C, 91% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.86 (s, 1H), 8.67 (d, J = 2.5 Hz, 1H), 8.59–8.53 (m, 1H), 7.05–6.84 (m, 10H), 6.68–6.62 (m, 1H), 6.17 (t, J = 7.5 Hz, 1H), 6.03 (s, 1H), 4.56 (d, J = 16.2 Hz, 2H), 3.42 (td, J = 11.0, 7.7 Hz, 1H), 2.96–2.87 (m, 3H), 2.29 (s, 2H), 2.25 (t, J = 5.5 Hz, 6H).13C NMR (100 MHz, Acetone-d6) δ 165.97, 151.15, 150.03, 146.58, 146.30, 145.92, 143.18, 142.39, 136.90, 136.33, 136.22, 135.05, 132.77, 130.68, 130.60, 129.35, 129.10, 128.79, 127.50, 126.25, 123.76), 117.81, 106.87, 83.36, 56.88, 49.94, 49.01, 44.33, 37.93, 20.78, 20.74. MS(ESI(+)) calcd for C31H30N4O+ [M + H]+: 475.25; found: 475.25.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(naphthalen-1-yl)methanone (b1): White solid, Melting Point: 142–144 °C, 94% Yield, 1H NMR (400 MHz, DMSO- d6), δ: 7.97 (d, J = 8.2 Hz, 2H), 7.64–7.35 (m, 10H), 7.32–7.10 (m, 4H), 7.01 (t, J = 7.7 Hz, 1H), 6.70 (t, J = 7.3 Hz, 1H), 6.21–6.04 (m, 2H), 4.73 (d, J = 16.9 Hz, 1H), 4.56 (d, J = 16.9 Hz, 1H), 3.43–3.28 (m, 2H), 3.14–2.88 (m, 2H), 2.10 (d, J = 16.3 Hz, 2H).13C NMR (100 MHz, DMSO- d6) δ 169.21, 150.84, 141.38, 139.45, 134.87, 134.44, 133.45, 131.59 (q, J = 35.3 Hz), 130.88, 130.03, 129.85, 129.73, 129.66, 129.41, 129.28, 129.15, 128.92, 128.61, 127.51, 126.95, 126.76, 126.14, 126.08, 125.71, 124.82 (q, J = 268.2 Hz), 124.24, 124.16, 123.90, 123.56, 118.11, 106.06, 82.29, 57.28, 49.56, 48.31, 43.77, 38.22. MS(ESI(+)) calcd for C37H28F6N2O+ [M + H]+: 631.22; found: 631.22.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(naphthalen-1-yl)methanone (b2): White solid, Melting Point: 161–163 °C, 92% Yield, 1H NMR (400 MHz, DMSO- d6), δ: 7.98 (dd, J = 3.2, 1.3 Hz, 1H), 7.50 (t, J = 8.2 Hz, 2H), 7.37–7.30 (m, 3H), 7.25 (t, J = 7.7 Hz, 2H), 7.18 (d, J = 7.2 Hz, 1H), 7.08 (s, 1H), 7.00–6.90 (m, 2H), 6.69 (td, J = 7.4, 0.8 Hz, 1H), 6.49 (d, J = 0.5 Hz, 1H), 6.18 (s, 2H), 6.04–5.91 (m, 1H), 4.54–4.39 (m, 1H), 4.38–4.26 (m, 1H), 3.60–3.42 (m, 1H), 3.32 (d, J = 8.0 Hz, 2H), 3.13 (d, J = 13.1 Hz, 2H), 2.27–2.13 (m, 2H).13C NMR (100 MHz, DMSO- d6) δ 168.88, 157.22, 150.89, 150.27, 139.55, 136.94, 134.14, 131.15 (q, J = 35.3 Hz), 130.61, 129.69, 129.58, 129.38, 129.27, 129.16, 129.09, 128.96, 128.76, 126.47, 126.07, 126.00, 124.22 (q, J = 268.2 Hz), 123.79, 123.61, 123.38, 117.96, 111.88, 105.98, 82.23, 57.04, 49.00, 44.05, 38.71. MS(ESI(+)) calcd for C32H26F6N4O+ [M + H]+: 597.21; found: 597.21.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(2-chloropyridin-4-yl)methanone (b3): Yellow oily, 89% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.53 (d, J = 5.0 Hz, 1H), 7.62 (d, J = 7.7 Hz, 3H), 7.49 (dd, J = 9.5, 7.3 Hz, 3H), 7.39 (d, J = 7.7 Hz, 1H), 7.26 (dd, J = 7.8, 7.1 Hz, 2H), 7.12 (td, J = 7.7, 1.2 Hz, 1H), 6.84 (d, J = 3.9 Hz, 1H), 6.24 (d, J = 7.9 Hz, 1H), 6.06 (s, 1H), 4.68 (d, J = 16.8 Hz, 1H), 4.57 (d, J = 16.8 Hz, 1H), 3.71 (ddd, J = 10.9, 5.6, 2.8 Hz, 1H), 3.55–3.42 (m, 2H), 3.28 (d, J = 13.2 Hz, 1H), 2.48–2.45 (m, 1H), 2.20–2.11 (m, 1H), 1.46–1.26 (m, 2H).13C NMR (100 MHz, Acetone-d6) δ 166.93, 151.96, 151.39, 150.93, 147.75, 141.76, 139.70, 134.35, 131.47 (q, J = 35.3 Hz), 131.05, 130.73, 130.41, 130.32, 129.84, 129.49, 129.34, 127.08, 127.04, 126.51, 126.41, 124.37 (q, J = 268.2 Hz), 123.96, 122.68, 121.27, 118.61, 106.79, 83.58, 57.61, 49.94, 49.43, 44.80, 38.59. MS(ESI(+)) calcd for C32H24ClF6N3O+ [M + H]+: 616.16; found: 616.16.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(3-chloropyridin-4-yl)methanone (b4): Yellow oily, 85% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.64 (s, 1H), 8.56 (d, J = 4.8 Hz, 1H), 7.63–7.47 (m, 4H), 7.46–7.34 (m, 3H), 7.24–7.11 (m, 4H), 7.03 (td, J = 7.7, 1.2 Hz, 1H), 6.74 (d, J = 3.9 Hz, 1H), 6.17 (d, J = 7.9 Hz, 1H), 5.96 (s, 1H), 4.63 (s, 1H), 4.57 (d, J = 16.7 Hz, 1H), 3.40 (d, J = 13.3 Hz, 1H), 3.35–3.29 (m, 1H), 3.26–3.21 (m, 1H), 2.39–2.34 (m, 2H).13C NMR (100 MHz, Acetone-d6)δ 165.29, 151.40, 150.26, 149.20, 144.08, 141.62, 139.63, 134.47, 131.61 (q, J = 35.3 Hz), 131.18, 129.89, 129.50, 129.44, 127.79, 127.19, 127.15, 124.34 (q, J = 268.2 Hz), 124.16, 124.11, 124.07, 124.02, 122.45, 118.76, 118.21, 106.85, 83.09, 58.02, 50.13, 48.01, 44.59, 38.62. MS(ESI(+)) calcd for C32H24ClF6N3O+ [M + H]+: 616.16; found: 616.16.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(5-methylpyrazin-2-yl)methanone (b5): Yellow oily, 88% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.74 (d, J = 1.4 Hz, 1H), 8.50–8.47 (m, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.51–7.27 (m, 6H), 7.18–7.10 (m, 2H), 7.02 (dd, J = 5.7, 1.7 Hz, 1H), 6.77–6.72 (m, 1H), 6.11 (d, J = 7.9 Hz, 1H), 6.03 (s, 1H), 4.63 (d, J = 16.7 Hz, 1H), 4.47 (d, J = 16.7 Hz, 1H), 3.54–3.45 (m, 1H), 3.37 (d, J = 13.2 Hz, 1H), 3.20 (d, J = 13.2 Hz, 1H), 2.56 (s, 3H), 2.40–2.29 (m, 2H).13C NMR (100 MHz, Acetone-d6) δ 166.39, 156.15, 151.29, 146.90, 146.09, 145.02, 142.77, 141.71, 139.81, 134.41, 131.81 (q, J = 35.3 Hz), 131.10, 129.77, 129.38, 129.33, 127.13, 127.10, 124.30 (q, J = 268.2 Hz), 124.07, 124.03, 123.99, 123.92, 118.55, 106.84, 83.94, 57.12, 50.28, 49.34, 44.77, 38.54, 21.48. MS(ESI(+)) calcd for C32H26F6N4O+ [M + H]+: 597.21; found: 597.21.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(pyrazin-2-yl)methanone (b6): Yellow oily, 86% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.59–8.54 (m, 1H), 7.89 (t, J = 7.7 Hz, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.57–7.40 (m, 6H), 7.36–7.29 (m, 2H), 7.22–7.14 (m, 2H), 7.02–6.98 (m, 1H), 6.77 (d, J = 7.3 Hz, 1H), 6.10 (d, J = 7.8 Hz, 1H), 6.03 (s, 1H), 4.64 (d, J = 16.6 Hz, 1H), 4.50 (d, J = 16.6 Hz, 1H), 3.53–3.44 (m, 1H), 3.37 (d, J = 13.1 Hz, 1H), 3.21 (d, J = 13.2 Hz, 1H), 2.38–2.28 (m, 2H).13C NMR (100 MHz, Acetone-d6) δ 167.79, 154.62, 151.20, 148.52, 141.58, 139.69, 137.36, 134.23, 131.70 (q, J = 35.3 Hz), 130.96, 129.57, 129.14, 126.96, 126.92, 125.69, 125.53, 125.39, 124.32 (q, J = 268.2 Hz), 124.09, 123.72, 118.26, 106.59, 83.63, 56.95, 50.03, 49.22, 44.65, 38.46. MS(ESI(+)) calcd for C31H24F6N4O+ [M + H]+: 583.19; found: 583.19.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(2-hydroxypyridin-3-yl)methanone (b7): White solid, Melting Point: 109–111 °C, 83% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 11.17 (s, 1H), 7.57–7.47 (m, 6H), 7.38 (dd, J = 7.8, 4.4 Hz, 2H), 7.32–7.26 (m, 2H), 7.19–7.15 (m, 3H), 6.99–6.95 (m, 1H), 6.71 (dd, J = 9.5, 5.3 Hz, 1H), 6.28 (t, J = 6.7 Hz, 1H), 6.04 (d, J = 8.0 Hz, 1H), 5.89 (s, 1H), 4.59 (d, J = 16.7 Hz, 1H), 4.47 (d, J = 16.8 Hz, 1H), 3.40–3.35 (m, 1H), 3.16 (d, J = 13.2 Hz, 1H), 2.32–2.25 (m, 2H).13C NMR (100 MHz, Acetone-d6)δ 167.20, 160.00, 151.53, 142.95, 141.83, 141.63, 140.51, 139.91, 137.75, 137.60, 134.52, 134.38, 131.71 (q, J = 35.3 Hz), 131.36, 129.81, 129.26, 127.09, 127.05, 124.23 (q, J = 268.2 Hz), 124.02, 123.82, 118.25, 106.58, 105.52, 83.14, 57.72, 50.08, 47.97, 44.91, 38.87. MS(ESI(+)) calcd for C32H25F6N3O2+ [M + H]+: 598.19; found: 598.19.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(2-chloropyridin-3-yl)methanone (b8): Yellow oily, 94% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.45 (dd, J = 4.8, 1.9 Hz, 1H), 7.64 (d, J = 4.8 Hz, 1H), 7.57 (d, J = 9.9 Hz, 3H), 7.54–7.37 (m, 4H), 7.34 (d, J = 7.7 Hz, 1H), 7.25–7.13 (m, 3H), 7.03 (td, J = 7.7, 1.1 Hz, 1H), 6.75 (t, J = 7.4 Hz, 1H), 6.17 (d, J = 7.9 Hz, 1H), 5.96 (s, 1H), 4.66 (d, J = 16.7 Hz, 1H), 4.59 (d, J = 16.7 Hz, 1H), 3.39 (t, J = 2.5 Hz, 1H), 3.22 (d, J = 7.4 Hz, 2H), 2.39–2.34 (m, 2H).13C NMR (100 MHz, Acetone-d6 )δ 166.06, 151.47, 150.91, 146.99, 141.71, 139.68, 137.75, 134.48, 133.59, 131.66 (q, J = 35.3 Hz), 131.21, 130.44, 130.39, 130.07, 129.87, 129.47, 129.44, 127.20, 127.16, 124.34 (q, J = 268.2 Hz), 124.08, 124.04, 124.00, 123.81, 118.69, 106.80, 83.08, 58.03, 50.08, 48.15, 44.66, 38.63. MS(ESI(+)) calcd for C32H24ClF6N3O+ [M + H]+: 616.16; found: 616.16.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(pyridin-2-yl)methanone (b9): Yellow oily, 92% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.56–8.51 (m, 1H), 7.92–7.86 (m, 1H), 7.69 (dd, J = 7.9, 2.8 Hz, 1H), 7.57–7.54 (m, 2H), 7.50–7.31 (m, 6H), 7.24 (d, J = 6.2 Hz, 1H), 7.17 (d, J = 5.0 Hz, 2H), 7.02–6.99 (m, 1H), 6.77–6.71 (m, 1H), 6.11 (t, J = 8.2 Hz, 1H), 6.03 (d, J = 3.9 Hz, 1H), 4.67–4.61 (m, 1H), 4.50 (d, J = 16.7 Hz, 1H), 4.03–3.96 (m, 1H), 3.37 (d, J = 13.2 Hz, 1H), 3.20 (dd, J = 13.3, 2.6 Hz, 1H), 2.37–2.28 (m, 2H).13C NMR (100 MHz, Acetone-d6) δ 167.98, 154.78, 151.37, 148.70, 141.75, 139.86, 137.54, 134.40, 131.87 (q, J = 35.3 Hz), 131.13, 129.75, 129.32, 129.30, 127.13, 127.09, 125.87, 125.72, 125.58, 124.51 (q, J = 268.2 Hz), 124.26, 124.12, 124.09, 123.90, 118.44, 106.77, 83.80, 57.13, 50.20, 49.41, 44.83, 38.64. MS(ESI(+)) calcd for C32H25F6N3O+ [M + H]+: 582.20; found: 582.20.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(pyridin-3-yl)methanone (b10): Yellow oily, 95% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.67–8.60 (m, 2H), 7.83 (d, J = 7.9 Hz, 1H), 7.59–7.24 (m, 8H), 7.23–7.11 (m, 3H), 7.03 (td, J = 7.6, 1.0 Hz, 1H), 6.75 (t, J = 7.4 Hz, 1H), 6.14 (d, J = 7.9 Hz, 1H), 6.05 (s, 1H), 4.60 (d, J = 16.8 Hz, 1H), 4.50 (d, J = 16.8 Hz, 1H), 3.72–3.62 (m, 1H), 3.38 (d, J = 13.2 Hz, 1H), 3.20 (d, J = 13.2 Hz, 1H), 2.42–2.30 (m, 2H).13C NMR (100 MHz, Acetone-d6)δ 168.21, 151.56, 151.26, 148.94, 141.58, 139.61, 135.36, 134.18, 132.50, 131.39 (q, J = 35.3 Hz), 130.83, 130.50, 129.61, 129.25, 129.12, 126.89, 126.86, 126.32, 126.23, 125.06, 124.17 (q, J = 268.2 Hz), 123.78, 123.74, 123.52, 118.30, 106.55, 83.22, 57.28, 49.69, 49.62, 44.67, 38.48. MS(ESI(+)) calcd for C32H25F6N3O+ [M + H]+: 582.20; found: 582.20.
3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(6-chloropyridin-2-yl)methanone (b11): Yellow oily, 87%, 1H NMR (400 MHz, Acetone-d6), δ: 7.96 (t, J = 7.8 Hz, 1H), 7.70–7.67 (m, 1H), 7.56 (d, J = 7.7 Hz, 3H), 7.51–7.38 (m, 4H), 7.32 (t, J = 6.8 Hz, 1H), 7.24 (d, J = 8.3 Hz, 1H), 7.20–7.15 (m, 2H), 7.02 (dd, J = 7.8, 4.2 Hz, 1H), 6.74 (dd, J = 9.1, 3.9 Hz, 1H), 6.13–6.10 (m, 1H), 6.01 (d, J = 5.1 Hz, 1H), 4.63 (d, J = 16.7 Hz, 1H), 4.48 (d, J = 16.7 Hz, 1H), 3.54–3.46 (m, 1H), 3.36 (d, J = 13.2 Hz, 1H), 3.20 (d, J = 13.2 Hz, 1H), 2.41–2.30 (m, 2H).13C NMR (100 MHz, Acetone-d6)δ 166.37, 154.91, 151.28, 149.97, 141.70, 140.98, 139.80, 134.39, 131.78 (q, J = 35.3 Hz), 131.10, 129.77, 129.59, 129.40, 129.31, 127.13, 127.09, 126.47, 124.29 (q, J = 268.2 Hz), 124.07, 123.93, 123.46, 118.57, 106.88, 83.97, 57.16, 50.25, 49.47, 44.76, 38.47. MS(ESI(+)) calcd for C32H24ClF6N3O+ [M + H]+: 616.16; found: 616.16.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(6-methylpyridin-3-yl)methanone (b12): White solid, Melting Point: 117–119 °C, 89% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.53 (s, 1H), 7.72 (dd, J = 8.0, 1.9 Hz, 1H), 7.57–7.29 (m, 7H), 7.27–7.12 (m, 4H), 7.05–7.00 (m, 1H), 6.75 (t, J = 7.4 Hz, 1H), 6.12 (d, J = 7.9 Hz, 1H), 6.05 (s, 1H), 4.58 (d, J = 16.8 Hz, 1H), 4.49 (d, J = 16.8 Hz, 1H), 3.47 (td, J = 11.1, 6.0 Hz, 1H), 3.37 (d, J = 13.2 Hz, 1H), 3.20 (d, J = 13.2 Hz, 1H), 2.50 (s, 3H), 2.35–2.31 (m, 2H).13C NMR (100 MHz, Acetone-d6) δ 168.61, 160.96, 151.46, 148.65, 141.77, 139.82, 136.01, 134.37, 131.60 (q, J = 35.3 Hz), 131.02, 130.68, 130.37, 130.27, 129.79, 129.43, 129.30, 127.09, 127.05, 126.51, 126.42, 124.35 (q, J = 268.2 Hz), 123.96, 123.92, 123.72, 122.92, 118.45, 106.72, 83.37, 57.42, 49.86, 44.87, 38.67, 24.28. MS(ESI(+)) calcd for C33H27F6N3O+ [M + H]+: 596.21; found: 596.21.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(4-methoxyphenyl)methanone(b13): Yellow oily, 90% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 7.54 (t, J = 6.5 Hz, 2H), 7.51–7.34 (m, 6H), 7.31 (d, J = 7.6 Hz, 1H), 7.22–7.15 (m, 2H), 7.10 (d, J = 6.0 Hz, 1H), 7.04–7.00 (m, 1H), 6.93 (d, J = 8.5 Hz, 2H), 6.74 (td, J = 7.5, 0.8 Hz, 1H), 6.09 (d, J = 7.0 Hz, 2H), 4.52 (dd, J = 2.3, 0.7 Hz, 2H), 3.82 (s, 3H), 3.71 (d, J = 0.6 Hz, 1H), 3.36 (d, J = 11.2 Hz, 1H), 3.19 (d, J = 13.2 Hz, 1H), 2.32 (d, J = 6.4 Hz, 2H).13C NMR (100 MHz, Acetone-d6)δ 170.21, 162.02, 151.52, 141.76, 139.91, 134.39, 131.73 (q, J = 35.3 Hz), 131.04, 130.67, 130.31, 129.95, 129.77, 129.36, 129.28, 128.95, 127.10, 127.07, 126.53, 126.44, 124.33 (q, J = 268.2 Hz), 123.97, 123.93, 123.89, 123.85, 118.34, 113.91, 106.66, 83.21, 57.28, 55.54, 50.18, 49.68, 44.91, 38.73. MS(ESI(+)) calcd for C34H28F6N2O2+ [M + H]+: 611.21; found: 611.21.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(5-methylpyridin-3-yl)methanone (b14): Yellow oily, 93% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.49–8.41 (m, 2H), 7.67–7.35 (m, 7H), 7.32 (d, J = 7.7 Hz, 1H), 7.22–7.14 (m, 3H), 7.03 (td, J = 7.7, 1.1 Hz, 1H), 6.75 (t, J = 7.4 Hz, 1H), 6.14 (d, J = 7.9 Hz, 1H), 6.05 (s, 1H), 4.60 (d, J = 16.8 Hz, 1H), 4.49 (d, J = 16.8 Hz, 1H), 3.45 (td, J = 11.0, 6.3 Hz, 1H), 3.38 (d, J = 13.2 Hz, 1H), 3.20 (d, J = 13.2 Hz, 1H), 2.37–2.31 (m, 5H).13C NMR (100 MHz, Acetone-d6)δ 168.54, 152.14, 151.45, 146.25, 141.83, 139.82, 135.69, 134.38, 133.44, 132.24, 131.61 (q, J = 35.3 Hz), 131.07, 129.82, 129.44, 129.32, 127.10, 127.06, 126.53, 126.43, 124.36 (q, J = 268.2 Hz), 123.93, 118.47, 106.70, 83.38, 57.47, 49.89, 49.79, 44.87, 38.67, 17.94. MS(ESI(+)) calcd for C33H27F6N3O+ [M + H]+: 596.21; found: 596.21.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(6-chloropyridin-3-yl)methanone (b15): Yellow oily, 94% Yield, 1H NMR (400 MHz, DMSO- d6), δ: 8.47 (d, J = 2.0 Hz, 1H), 7.94 (dd, J = 8.3, 2.4 Hz, 1H), 7.63–7.50 (m, 3H), 7.47 (s, 1H), 7.40 (td, J = 7.7, 3.7 Hz, 2H), 7.29 (d, J = 7.7 Hz, 1H), 7.23 (d, J = 6.7 Hz, 1H), 7.12 (s, 1H), 7.08–6.98 (m, 2H), 6.75 (t, J = 7.3 Hz, 1H), 6.12 (d, J = 7.8 Hz, 1H), 5.93 (s, 1H), 4.46–4.35 (m, 2H), 3.57 (dd, J = 10.6, 6.6 Hz, 1H), 3.38 (d, J = 7.9 Hz, 2H), 3.14 (d, J = 13.2 Hz, 1H), 2.28 (dt, J = 11.8, 7.0 Hz, 2H).13C NMR (100 MHz, DMSO- d6) δ 166.74, 152.13, 150.76, 149.08, 141.11, 139.37, 139.28, 134.13, 131.40 (q, J = 35.3 Hz), 131.15, 130.67, 129.72, 129.59, 129.28, 129.16, 128.77, 126.50, 126.06, 126.00, 124.53 (q, J = 268.2 Hz), 124.18, 123.81, 123.60, 123.50, 118.08, 106.19, 82.63, 56.92, 49.33, 49.18, 44.04, 38.37. MS(ESI(+)) calcd for C32H24ClF6N3O+ [M + H]+: 616.16; found: 616.16.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(5,6-dichloropyridin-3-yl)methanone (b16): Yellow oily, Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.39 (d, J = 1.9 Hz, 1H), 8.00 (d, J = 1.9 Hz, 1H), 7.59–7.32 (m, 6H), 7.28 (d, J = 7.7 Hz, 1H), 7.18–7.10 (m, 3H), 7.04–6.98 (m, 1H), 6.73 (t, J = 7.4 Hz, 1H), 6.14 (d, J = 7.9 Hz, 1H), 5.99 (s, 1H), 4.55 (d, J = 16.8 Hz, 1H), 4.46 (d, J = 16.8 Hz, 1H), 3.76–3.70 (m, 1H), 3.35 (d, J = 13.2 Hz, 1H), 3.16 (d, J = 13.2 Hz, 1H), 2.38–2.28 (m, 2H).13C NMR (100 MHz, Acetone-d6)δ 165.74, 151.21, 149.98, 146.79, 141.55, 139.51, 138.46, 134.15, 133.19, 131.27 (q, J = 35.3 Hz), 130.86, 130.55, 130.51, 130.17, 130.11, 129.65, 129.30, 129.15, 127.39, 126.88, 126.85, 124.18 (q, J = 268.2 Hz), 123.80, 123.77, 118.39, 106.60, 83.36, 57.36, 49.66, 49.49, 44.63, 38.43. MS(ESI(+)) calcd for C32H23Cl2F6N3O+ [M + H]+: 650.12; found: 650.12.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(5-chloropyrazin-2-yl)methanone (b17): Yellow oily, 83% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.76–8.60 (m, 2H), 7.57–7.47 (m, 3H), 7.47–7.33 (m, 3H), 7.31 (d, J = 7.5 Hz, 1H), 7.24–7.15 (m, 3H), 7.05–7.00 (m, 1H), 6.75 (td, J = 7.4, 0.7 Hz, 1H), 6.13 (d, J = 7.8 Hz, 1H), 6.02 (s, 1H), 4.63 (d, J = 16.7 Hz, 1H), 4.47 (d, J = 16.7 Hz, 1H), 3.50 (dt, J = 11.6, 3.6 Hz, 1H), 3.39–3.33 (m, 1H), 3.23–3.18 (m, 1H), 2.36 (dd, J = 12.1, 5.7 Hz, 2H).13C NMR (100 MHz, Acetone-d6) δ 165.24, 151.21, 150.49, 148.14, 145.66, 143.10, 141.62, 139.72, 134.40, 131.71 (q, J = 35.3 Hz), 131.09, 129.80, 129.44, 129.35, 127.13, 127.09, 124.31 (q, J = 268.2 Hz), 124.03, 124.00, 123.96, 123.93, 118.66, 106.89, 84.01, 57.20, 50.28, 49.35, 44.70, 38.42. MS(ESI(+)) calcd for C31H23ClF6N4O+ [M + H]+: 617.15; found: 617.15.
(3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(2-fluoropyridin-3-yl)methanone (b18): Yellow oily, 88% Yield, 1H NMR (400 MHz, Acetone-d6), δ: 8.30 (d, J = 4.9 Hz, 1H), 7.96–7.83 (m, 1H), 7.54 (dd, J = 14.4, 7.1 Hz, 3H), 7.44–7.37 (m, 3H), 7.36–7.06 (m, 5H), 7.02 (dd, J = 14.0, 6.4 Hz, 1H), 6.75 (t, J = 7.4 Hz, 1H), 6.11 (d, J = 7.9 Hz, 1H), 5.96 (s, 1H), 4.62 (d, J = 16.7 Hz, 1H), 4.46 (d, J = 16.7 Hz, 1H), 3.60–3.50 (m, 1H), 3.42–3.37 (m, 1H), 3.25–3.16 (m, 1H), 2.44–2.32 (m, 2H).13C NMR (100 MHz, Acetone-d6) δ 164.57, 160.66, 158.30, 151.45, 149.88, 149.73(CH, d, J = 13.0 Hz ), 141.64, 141.14, 141.10, 139.73, 134.36, 131.53 (q, J = 35.3 Hz), 131.01, 129.81, 129.48, 129.34, 127.08, 127.04, 124.36 (q, J = 268.2 Hz), 124.00, 122.74, 122.70, 120.24(d, J = 31.9 Hz ), 119.91, 118.67, 106.86, 83.43, 57.85, 50.23, 48.50, 44.84, 38.42. MS(ESI(+)) calcd for C32H24F7N3O+ [M + H]+: 600.19; found: 600.19.
3a,8-bis(3-(trifluoromethyl)benzyl)-3,3a,8,8a-tetrahydropyrrolo[2,3-b]indol-1(2H)-yl)(pyridin-4-yl)methanone(b19): Yellow oily, 90% Yield, 1H NMR (400 MHz, DMSO- d6), δ: 8.64 (dd, J = 4.5, 1.4 Hz, 2H), 7.53 (d, J = 7.7 Hz, 2H), 7.45 (s, 1H), 7.40–7.33 (m, 4H), 7.27 (d, J = 7.6 Hz, 1H), 7.20 (d, J = 7.3 Hz, 1H), 7.10 (s, 1H), 7.00 (d, J = 6.9 Hz, 2H), 6.72 (t, J = 7.4 Hz, 1H), 6.08 (d, J = 7.8 Hz, 1H), 5.88 (s, 1H), 4.44 (d, J = 16.9 Hz, 2H), 3.45 (dd, J = 10.5, 6.2 Hz, 1H), 3.29 (d, J = 5.4 Hz, 2H), 3.13 (d, J = 13.1 Hz, 1H), 2.29–2.19 (m, 2H).13C NMR (100 MHz, DMSO- d6)δ 167.84, 150.74, 150.46, 143.56, 141.13, 139.39, 134.15, 131.17 (q, J = 35.3 Hz), 130.68, 129.75, 129.61, 129.30, 129.17, 129.09, 128.78, 126.51, 126.08, 126.01, 124.18 (q, J = 268.2 Hz), 123.83, 123.63, 123.44, 123.31, 121.83, 118.11, 106.19, 82.65, 56.98, 49.28, 49.12, 43.98, 38.33. MS(ESI(+)) calcd for C32H25F6N3O+ [M + H]+: 582.20; found: 582.20.