M.Z. Wróbel et al. / European Journal of Medicinal Chemistry 63 (2013) 484e500
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3
3
3J2 ¼ 7.0, 4J ¼ 1.0), 7.36 (C70H, dt, 3J ¼ 8.0, 4J ¼ 5J ¼ 1.0), 3.63 (C1xH2, t,
3J ¼ 7.0), 1.63 (C2xH2, C3xH2, m), 2.61 (C4xH2, t, 3J ¼ 7.5), 3.13
(CaH(E), CeH(E), m), 2.27 (CaH(A), CeH(A), m), 1.97 (CbH2, CdH2, m),
2.76 (CcH, m), 6.85 (C200H, d, 3J ¼ 2.0), 7.02 (C400H, d, 4J ¼ 2.5), 6.84
(C600H, dd, 3J ¼ 9.0, 4J ¼ 2.5), 7.24 (C700H, dd, 3J ¼ 9.0, 5J ¼ 0.5), 3.86
(OCH3, s), 8.86 (N10H, bs), 8.27 (N100H, bs).
2J ¼ 18.0, J ¼ 9.5), 7.14 (C20H, d, J ¼ 2.0), 7.44 (C40H, dd, 3J ¼ 8.0,
4J ¼ 1.0), 7.22 (C60H, m, 3J1 ¼ 8.5, 3J2 ¼ 7.0, 4J ¼ 1.0), 7.38 (C70H, dt,
3J ¼ 8.0, 4J ¼ 5J ¼ 1.0), 3.70 (C1xH2, t, 3J ¼ 7.0), 1.93 (C2xH2, m), 2.49
(C3xH2, t, 3J ¼ 7.5), 3.05 (CaH(E), CeH(E), m), 2.14 (CaH(A), CeH(A),
m), 2.03 (CbH(E), CdH(E), m), 1.79 (CbH(A), CdH(A), m), 2.77 (CcH,
tt, 3J1 ¼ 11.5, 3J2 ¼ 3.5), 6.87 (C200H, d, J ¼ 2.0), 7.05 (C400H, d,
3
13C NMR (125 Hz, CDCl3): 178.5 (C2), 38.2 (C3), 36.3 (C4), 176.6
(C5), 122.3 (C20), 111.4 (C30), 125.8 (C30a), 118.5 (C40), 120.0 (C50),
122.6 (C60),111.8 (C70),136.7 (C70a), 38.2 (C1x), 25.5 (C2x), 23.1 (C3x),
57.2 (C4x), 53.3 and 53.5 (Ca, Ce), 31.1 (Cb, Cd), 32.5 (Cc), 121.0 (C200),
199.5 (C300), 126.7 (C300a), 101.0 (C400), 153.8 (C500), 112.0 (C600), 112.0
(C700), 131.6 (C700a), 56.1 (OCH3).
4J ¼ 2.5), 6.84 (C600H dd, 3J ¼ 8.5, 4J ¼ 2.5), 7.23 (C700H, d, 3J ¼ 9.0),
3.86 (OCH3, s), 8.34 (N10H, bs), 7.91 (N100H, bs).
13C NMR (125 Hz, CDCl3): 178.2 (C2), 37.6 (C3), 36.4 (C4), 176.5
(C5), 122.2 (C20), 111.6 (C30), 125.7 (C30a), 118.6 (C40), 120.1 (C50),
122.7 (C60),111.7 (C70),136.7 (C70a), 38.2 (C1x), 25.1 (C2x), 56.3 (C3x),
54.3 (Ca, Ce), 32.7 and 32.7 (Cb, Cd), 33.3 (Cc), 120.6 (C200), 120.9
(C300), 127.0 (C300a), 101.2 (C400), 153.8 (C500), 112.0 (C600), 111.9 (C700),
136.7 (C700a), 56.1 (OCH3).
HRMS (MSESþ) calcd for
C30H34N4O3H 499.2709; Found:
499.2698.
HRMS (MSESþ) calcd for
C29H32N4O3H 485.2553; Found:
4.1.8.19. 1-{3-[4-(1H-Indol-3-yl)piperidin-1-yl]propyl}-3-(1H-indol-
3-yl)pyrrolidine-2,5-dione (33). The title compound was isolated as
a yellow powder. Yield: 65.8% 0.15 g, m.p. 111e117 ꢁC.
485.2532.
4.1.8.22. 1-{2-[4-(1H-Indol-3-yl)piperidin-1-yl]ethyl}-3-(1H-indol-
3-yl)pyrrolidine-2,5-dione (36). The title compound was isolated as
a yellow powder. Yield: 45.2% 0.10 g, m.p. 97e105 ꢁC (melts with
decomposition).
1H NMR (500 Hz, CDCl3): 4.29 (C3H, 4d, 3J1 ¼ 10.0, 3J2 ¼ 5.0,
4J ¼ 0.5), 2.93 (C4H(1), dd, 2J ¼ 18.5, 3J ¼ 5.0), 3.26 (C4H(2), dd,
3
2J ¼ 18.5, J ¼ 10.0), 7.13 (C20H, C50H, m), 7.44 (C40H, dd, 3J ¼ 8.0,
4J ¼ 1.0), 7.22 (C60H, m, 3J1 ¼ 8.0, 3J2 ¼ 7.0, J ¼ 1.0), 7.37 (C70H, dt,
1H NMR (500 Hz, CDCl3): 4.18 (C3H, dd, 3J1 ¼ 9.5, 3J2 ¼ 5.0), 2.89
(C4H(1), dd, 2J ¼ 18.5, 3J ¼ 5.0), 3.15 (C4H(2), dd, 2J ¼ 18.0, 3J ¼ 9.5),
7.09 (C20H, C50H, C500H, m), 7.48 (C40H, d, 3J ¼ 8.0), 7.17 (C60H, C600H),
7.32 (C70H, C700H, m), 3.82 (C1xH2, m), 2.70 (C2xH2, m), 3.15 (CaH(E),
Ce(E), m), 2.19 (CaH(A), CeH(A), m), 2.04 (CbH(E), CdH(E), m), 1.74
(CbH(A), CdH(A), m), 2.82 (CcH, tt, 3J1 ¼ 12.0, 3J2 ¼ 3.5), 6.85 (C200H,
d, 3J ¼ 2.0), 7.60 (C400H, d, 3J ¼ 8.0), 8.29 (N10H, bs), 8.11 (N100H, bs).
13C NMR (125 Hz, CDCl3): 178.4 (C2), 36.5 (C3), 36.4 (C4), 176.6
(C5),122.6 (C20),111.8 (C30),125.6 (C30a),118.6 (C40), 120.0 (C50),122.6
(C60),111.6 (C70),136.4 (C70a), 38.2 (C1x), 55.4 (C2x), 54.3 and 54.4 (Ca,
Ce), 32.9 and 33.0 (Cb, Cd), 33.4 (Cc), 119.7 (C200), 121.4 (C300), 126.7
(C300a), 119.0 (C400), 119.1 (C500), 121.9 (C600), 111.2 (C700), 136.6 (C700a).
4
3J ¼ 8.0, 4J ¼ 5J ¼ 1.0), 3.70 (C1xH2, t, 3J ¼ 7.0), 1.92 (C2xH2, m), 2.49
(C3xH2, t, 3J ¼ 7.5), 3.05 (CaH(E), CeH(E), m), 2.12 (CaH(A), CeH(A),
m), 2.04 (CbH(E), CdH(E), m), 1.80 (CbH(A), CdH(A), m), 2.82 (CcH,
tt, 3J1 ¼12.0, 3J2 ¼ 4.0), 6.88 (C200H, dd, 3J ¼ 2.5, 4J ¼ 0.5), 7.62 (C400H,
dd, 3J ¼ 8.0, 4J ¼ 1.0), 7.09 (C500H, m, 3J1 ¼ 8.0, 3J2 ¼ 7.0, 4J ¼ 1.0), 7.17
4
(C600H, m, 3J1 ¼ 8.0, 3J2 ¼ 7.0, J ¼ 1.0), 7.34 (C700H, dt, 3J ¼ 8.0,
4J ¼ 5J ¼ 1.0), 8.33 (N10H, bs), 8.03 (N100H, bs).
13C NMR (125 Hz, CDCl3): 178.2 (C2), 37.6 (C3), 36.4 (C4), 176.5
(C5), 122.2 (C20), 111.6 (C30), 125.7 (C30a), 118.6 (C40), 120.1 (C50),
122.7 (C60),111.7 (C70),136.4 (C70a), 38.2 (C1x), 25.1 (C2x), 56.3 (C3x),
54.3 (Ca, Ce), 32.8 and 32.8 (Cb, Cd), 33.3 (Cc), 119.7 (C200), 121.2
(C300), 126.6 (C300a), 119.0 (C400), 119.1 (C500), 121.9 (C600), 111.2 (C700),
136.6 (C700a).
HRMS (MSESþ) calcd for
C27H28N4O2H 441.2291; Found:
441.2282.
HRMS (MSESþ) calcd for
C28H30N4O2H 455.2447; Found:
455.2459.
4.1.8.23. 1-{2-[4-(5-Fluoro-1H-indol-3-yl)piperidin-1-yl]ethyl}-3-
(1H-indol-3-yl)pyrrolidine-2,5-dione (37). The title compound was
isolated as a yellow powder. Yield: 60.8% 0.10 g, m.p. 108e116 ꢁC.
1H NMR (500 Hz, CDCl3): 4.16 (C3H, dd, 3J1 ¼ 9.5, 3J2 ¼ 5.0), 2.87
(C4H(1), dd, 2J ¼ 18.5, 3J ¼ 5.0), 3.13 (C4H(2), dd, 2J ¼ 18.5, 3J ¼ 9.5),
4.1.8.20. 1-{3-[4-(5-Fluoro-1H-indol-3-yl)piperidin-1-yl]propyl}-3-
(1H-indol-3-yl)pyrrolidine-2,5-dione (34). The title compound was
isolated as a yellowish powder. Yield: 74.5% 0.17 g, m.p. 109e116 ꢁC
(melts with decomposition).
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7.06 (C20H, d, J ¼ 2.5), 7.46 (C40H, d, J ¼ 8.0), 7.09 (C50H, m,
3J1 ¼ 8.0, 3J2 ¼ 7.0 4J ¼ 1.0), 7.17 (C60H, m, 3J1 ¼ 8.0, 3J2 ¼ 7.0, 4J ¼ 1.0),
7.31 (C70H, d, 3J ¼ 8.5), 3.82 (C1xH2, t, 3J ¼ 6.5), 2.69 (C2xH2, t,
3J ¼ 6.5), 3.16 (CaH(E), Ce(E), m), 2.17 (CaH(A), Ce(A), m), 1.98
(CbH(E), CdH(E), m), 1.69 (CbH(A), CdH(A), m), 2.72 (CcH, tt,
3J1 ¼12.0, 3J2 ¼ 4.0), 6.83 (C200H, d, 3J ¼ 2.5), 7.19e7.23 (C400H, C700H,
m), 6.90 (C600H, td, 3J ¼ 9.0, 4J ¼ 2.5), 8.42 (N10H, bs), 8.23 (N100H, bs).
13C NMR (500 Hz, CDCl3): 178.5 (C2), 36.5 (C3), 36.3 (C4), 176.6
(C5), 122.6 (C20),111.8 (C30),125.6 (C30a), 118.5 (C40),121.6 (C50), 122.6
(C60),111.6 (C70),136.6 (C70a), 38.2 (C1x), 55.4 (C2x), 54.2 and 54.2 (Ca,
Ce), 32.7 and 32.8 (Cb, Cd), 33.3 (Cc), 120.0 (C200), 121.4 (C300, d*,
4J ¼ 4.9),126.9 (C300a, d*, 3J ¼ 9.3),103.9 (C400, d*, 2J ¼ 23.4),157.5 (C500,
d*, 1J ¼ 233.9), 110.1 (C600, d*, 2J ¼ 26.3), 111.7 (C700), 132.9 (C700a).
HRMS (MSESþ) calcd for C27H27FN4O2H 459.2196; Found:
459.2187.
1H NMR (500 Hz, CDCl3): 4.30 (C3H, dd, 3J1 ¼ 9.5, 3J2 ¼ 5.0), 2.94
(C4H(1), dd, 3J ¼ 18.5, 3J ¼ 5.0), 3.26 (C4H(2), dd, 3J ¼ 18.5, 3J ¼ 9.5),
7.15 (C20H, d, 3J ¼ 2.0), 7.44 (C40H, d, 3J ¼ 8.0), 7.13 (C50H, t, 3J ¼ 8.0),
7.24 (C606, C400H, C700H, m), 7.38 (C70H, d, 3J ¼ 8.0), 3.70 (C1xH2, t,
3J ¼ 7.0), 1.77 (C2xH2, m), 2.48 (C3xH2, t, 3J ¼ 7.0), 3.04 (CaH(E),
CeH(E), pd), 2.08 (CaH(A), CeH(A), pt), 1.79 (CbH(E), CdH(E), pd),
1.92 (CbH(A), CdH(A), m), 2.74 (CcH, tt, 3J1 ¼ 12.0, 3J2 ¼ 3.5), 6.92
(C200H, C600H, m), 8.27 (N10H, bs), 8.00 (N100H, bs).
13C NMR (125 Hz, CDCl3): 178.2 (C2), 37.6 (C3), 36.4 (C4), 176.4
(C5), 122.2 (C20),111.8 (C30), 132.8 (C30a), 118.6 (C40),120.1 (C50),122.7
(C60), 111.7 (C70), 136.6 (C70a), 38.2 (C1x), 25.1 (C2x), 56.3 (C3x), 54.3
(Ca, Ce), 32.7 and 32.8 (Cb, Cd), 33.3 (Cc),121.5 (C200),125.7 (C300),127.0
(C300a, d*, 3J ¼ 9.3),103.9 (C400, d*, 2J ¼ 23.5),157.5 (C500, d*, 1J ¼ 234.3),
110.2 (C600, d*, 2J ¼ 26.5), 111.7 (C700, d*, 3J ¼ 9.7), 136.6 (C700a).
HRMS (MSESþ) calcd for C28H29FN4O2H 473.2353; Found:
473.2347.
4.1.8.24. 1-{2-[4-(5-Methoxy-1H-indol-3-yl)piperidin-1-yl]ethyl}-3-
(1H-indol-3-yl)pyrrolidine-2,5-dione (38). The title compound was
isolated as a yellow powder. Yield: 42.4% 0.10 g, m.p. 111e119 ꢁC.
1H NMR (500 Hz, CDCl3): 4.15 (C3H, dd, 3J1 ¼ 9.5, 3J2 ¼ 5.0), 2.86
(C4H(1), dd, 2J ¼ 18.5, 3J ¼ 5.0), 3.13 (C4H(2), dd, 2J ¼ 18.0, 3J ¼ 9.5),
7.05 (C20H, d, 3J ¼ 2.5), 7.47 (C40H, d, 3J ¼ 8.0), 7.09 (C50H, m, 3J1 ¼7.5,
4.1.8.21. 1-{3-[4-(5-Methoxy-1H-indol-3-yl)piperidin-1-yl]propyl}-
3-(1H-indol-3-yl)pyrrolidine-2,5-dione (35). The title compound
was isolated as a yellow powder. Yield: 61.7% 0.15 g, m.p. 106e
111 ꢁC.
1H NMR (500 Hz, CDCl3): 4.29 ( C3H, 4d, 3J1 ¼ 9.5, 3J2 ¼ 5.0,
3J2 ¼ 7.0 J ¼ 1.0), 7.17 (C60H, m, 3J1 ¼ 8.5, 3J2 ¼ 7.0 4J ¼ 1.5), 7.31
4
4J ¼ 0.5), 2.94 (C4H(1), dd, 2J ¼ 18.0, 3J ¼ 5.0), 3.26 (C4H(2), dd,
(C70H, dt, 3J ¼ 8.5, 4J ¼ 5J ¼ 1.0), 3.82 (C1xH2, t, 3J ¼ 6.0), 2.70 (C2xH2,