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D. S. El-Gamil et al.
Arch. Pharm. Chem. Life Sci. 2013, 346, 23–33
7.01 (m, 1H, Ar), 6.92 (dt, J ¼ 2.3, 1.4 Hz, 1H, Ar), 6.45 (s, 1H,
NCHCS), 4.49 (dd, J ¼ 11.0, 5.5 Hz, 1H, CHC(O)N), 3.42 (t, J ¼ 7.1,
2H, CH2 CH2CH2CH3), 3.35 (dd, J ¼ 15.0, 5.5 Hz, 1H, NCHCHaHb),
2.79 (ddd, J ¼ 15.1, 11.0, 1.8 Hz, 1H, NCHCHaHb), 1.56–1.48
(m, 2H, CH2 CH2CH2CH3), 1.29–1.23 (m, 2H, CH2 CH2CH2CH3),
0.87 ppm (t, J ¼ 7.5 Hz, 3H, CH2CH2CH2CH3). 13C NMR (125 MHz,
DMSO-d6): d 172.23, 154.12 (NCO), 144.65, 136.62, 130.17, 130.05,
127.46, 125.54, 122.01, 118.95, 118.42, 111.56, 111.48, 106.25,
52.40 (C5), 46.64 (C11a), 37.71, 29.59, 22.46, 19.33, 13.46 ppm
(CH3). IR: 3317.76 (–NH–), 1764.58, 1695.60 cmꢁ1 (–CO–). HPLC/
MS (ESI): Purity 100%, for C21H20BrN3O2S: m/z (%): 459 [Mþþ2],
457 [Mþ] (100%).
(5R,11aS) 5-(5-Bromo-2-thienyl)-2-ethyl-5,6,11,11a-
tetrahydro-1H-imidazo[10,5 0:1,6]pyrido[3,4-b]indole-
1,3(2H)-dione (7)
Dark yellow powder (0.14 g, 32.9%): Rf ¼ 0.26 (CH2Cl2); mp: 193–
1968C; 1H NMR (500 MHz, DMSO-d6): d 10.90 (s, 1H, NH), 7.57–7.54
(m,1H, Ar), 7.29 (dt, J ¼ 8.1, 0.9 Hz, 1H, Ar), 7.13–7.07 (m, 3H, Ar),
7.02 (ddd, J ¼ 8.0, 7.0, 1.0 Hz, 1H, Ar), 6.23 (s, 1H, NCHCS), 4.50
(dd, J ¼ 11.5, 4.3 Hz, 1H, CHC(O)N), 3.42 (qd, J ¼ 7.2, 3.3 Hz,
2H, CH2CH3), 3.32–3.28 (m, 1H, NCHCHaHb), 2.85 (ddd, J ¼ 14.8,
11.6, 1.8 Hz, 1H, NCHCHaHb), 1.11 ppm (t, J ¼ 7.2 Hz, 3H,
CH2CH3). 13C NMR (125 MHz, DMSO-d6): d 171.05, 154.23 (NCO),
146.08, 136.63, 133.51, 129.52, 127.45, 125.72, 121.77, 118.94,
118.39, 111.43, 111.11, 105.19, 57.57 (C5), 51.47 (C11a), 32.67
(CH2CH3), 21.68 (CHaHb), 13.28 ppm (CH2CH3). IR: 3328.56 (–NH–),
1764.73, 1697.84 cmꢁ1 (–CO–). HPLC/MS (ESI): Purity 100%,
for C19H16BrN3O2S: m/z (%) 431 [Mþþ2], 429 [Mþ], 242 (100%).
(5R,11aS) 5-(5-Bromo-2-thienyl)-2-butyl-5,6,11,11a-
tetrahydro-1H-imidazo[10,5 0:1,6]pyrido[3,4-b]indole-
1,3(2H)-dione (11)
Yellow powder (0.27 g, 58.7%): Rf ¼ 0.35 (CH2Cl2); mp: 181–
1838C; 1H NMR (500 MHz, DMSO-d6): d 10.90 (s, 1H, NH), 7.56–
7.53 (m, 1H, Ar), 7.29 (dt, J ¼ 8.1, 0.9 Hz, 1H, Ar), 7.13–7.07
(m, 3H, Ar), 7.02 (ddd, J ¼ 8.0, 7.0, 1.0 Hz, 1H, Ar), 6.23 (s, 1H,
NCHCS), 4.52 (dd, J ¼ 11.5, 4.3 Hz, 1H, CHC(O)N), 3.39 (t, J ¼ 7.1,
2H, CH2 CH2CH2CH3), 3.34–3.29 (m, 1H, NCHCHaHb), 2.84
(ddd, J ¼ 14.8, 11.6, 1.8 Hz, 1H, NCHCHaHb), 1.52–1.46 (m, 2H,
CH2 CH2CH2CH3), 1.29–1.24 (m, 2H, CH2 CH2CH2CH3), 0.88 ppm
(t, J ¼ 7.3 Hz, 3H, CH2CH2CH2CH3). 13C NMR (125 MHz, DMSO-d6):
d 171.28, 154.34 (NCO), 146.13, 136.62, 133.52, 129.52, 127.40,
125.69, 121.77, 118.94, 118.39, 111.43, 111.08, 105.36, 57.65 (C5),
51.26 (C11a), 37.45, 29.58, 21.78, 19.28, 13.45 ppm (CH3).
IR: 3303.53 (–NH–), 1755.54, 1697.13 cmꢁ1 (–CO–). HPLC/MS
(ESI): Purity 100%, for C21H20BrN3O2S: m/z (%): 459 [Mþþ2], 457
[Mþ] (100%).
(5S,11aS) 5-(5-Bromo-2-thienyl)-2-ethyl-5,6,11,11a-
tetrahydro-1H-imidazo[10,5 0:1,6]pyrido[3,4-b]indole-
1,3(2H)-dione (8)
Yellow powder (0.25 g, 58.4%): Rf ¼ 0.48 (CH2Cl2); mp: 135–
1388C; 1H NMR (500 MHz, DMSO-d6): d 11.10 (s, 1H, NH), 7.54
(m, 1H, Ar), 7.34 (dt, J ¼ 8.2, 0.9 Hz, 1H, Ar), 7.15–7.10 (m, 2H, Ar),
7.03 (ddd, J ¼ 8.0, 7.0, 1.0 Hz, 1H, Ar), 6.92 (dd, J ¼ 3.8, 0.7 Hz,
1H, Ar), 6.45 (s, 1H, NCHCS), 4.48 (dd, J ¼ 10.9, 5.7 Hz,
1H, CHC(O)N), 3.46 (q, J ¼ 7.2, 2H, CH2CH3), 3.37–3.32
(dd, J ¼ 15.0, 5.5 Hz, 1H, NCHCHaHb), 2.80 (ddd, J ¼ 15.1, 10.9,
1.7 Hz, 1H, NCHCHaHb), 1.12 ppm (t, J ¼ 7.2 Hz, 3H, CH2CH3).
13C NMR (125 MHz, DMSO-d6): d 171.98, 153.94 (NCO), 144.65,
136.62, 130.16, 130.05, 127.50, 125.54, 122.00, 118.94, 118.41,
111.60, 111.54, 106.25, 52.43 (C5), 46.61 (C11a), 33.05 (CH2CH3),
22.31 (CHaHb), 13.24 ppm (CH2CH3). IR: 3316.6 (–NH–),
1765.74, 1695.22 cmꢁ1 (–CO–). HPLC/MS (ESI): Purity 97.62%,
for C19H16BrN3O2S: m/z (%): 431 [Mþþ2], 429 [Mþ] (100%).
(5S,11aS) 5-(5-Bromo-2-thienyl)-2-butyl-5,6,11,11a-
tetrahydro-1H-imidazo[10,5 0:1,6]pyrido[3,4-b]indole-
1,3(2H)-dione (12)
Yellow powder (0.31 g, 67.4%): Rf ¼ 0.62 (CH2Cl2); mp: 98–1018C;
1H NMR (500 MHz, DMSO-d6): d 11.11 (s, 1H, NH), 7.56–7.53
(m, 1H, Ar), 7.34 (dt, J ¼ 8.1, 0.9 Hz, 1H, Ar), 7.15–7.10 (m, 2H,
Ar), 7.03 (ddd, J ¼ 8.0, 7.0, 1.0 Hz, 1H, Ar), 6.91 (dd, J ¼ 3.8,
0.8 Hz, 1H, Ar), 6.45 (s, 1H, NCHCS), 4.49 (dd, J ¼ 11.0, 5.6 Hz,
1H, CHC(O)N), 3.42 (t, J ¼ 7.1, 2H, CH2 CH2CH2CH3), 3.36
(dd, J ¼ 15.0, 5.5 Hz, 1H, NCHCHaHb), 2.79 (ddd, J ¼ 15.1, 11.0,
1.8 Hz, 1H, NCHCHaHb), 1.56–1.49 (m, 2H, CH2 CH2CH2CH3), 1.29–
1.24 (m, 2H, CH2 CH2CH2CH3), 0.88 ppm (t, J ¼ 7.4 Hz, 3H,
(5S,11aR) 5-(5-Bromo-2-thienyl)-2-butyl-5,6,11,11a-
tetrahydro-1H-imidazo[10,5 0:1,6]pyrido[3,4-b]indole-
1,3(2H)-dione (9)
Yellow powder (0.2 g, 43.4%): Rf ¼ 0.35 (CH2Cl2); mp: 178–1818C;
1H NMR (500 MHz, DMSO-d6): d 10.90 (s, 1H, NH), 7.57–7.54
(m, 1H, Ar), 7.29 (dt, J ¼ 8.1, 0.9 Hz, 1H, Ar), 7.13–7.07 (m, 3H,
Ar), 7.02 (ddd, J ¼ 8.0, 7.1, 1.1 Hz, 1H, Ar), 6.23 (s, 1H, NCHCS),
4.52 (dd, J ¼ 11.5, 4.3 Hz, 1H, CHC(O)N), 3.39 (t, J ¼ 7.1, 2H, CH2
CH2CH2CH3), 3.34–3.28 (m, 1H, NCHCHaHb), 2.84 (ddd, J ¼ 14.8,
11.6, 1.8 Hz, 1H, NCHCHaHb), 1.52–1.46 (m, 2H, CH2 CH2CH2CH3),
1.29–1.24 (m, 2H, CH2 CH2CH2CH3), 0.88 ppm (t, J ¼ 7.4 Hz, 3H,
CH2CH2CH2CH3). 13C NMR (125 MHz, DMSO-d6): d 171.28, 154.48
(NCO), 146.11, 136.74, 133.46, 129.49, 127.51, 125.75, 121.77,
119.05, 118.39, 111.43, 111.10, 105.42, 57.71 (C5), 51.31 (C11a),
37.45, 29.64, 21.82, 19.31, 13.45 ppm (CH3). IR: 3304.49 (–NH–),
1755.60, 1698.53 cmꢁ1 (–CO–). HPLC/MS (ESI): Purity 99.5%,
for C21H20BrN3O2S: m/z (%): 459 [Mþþ2], 457 [Mþ] (100%).
CH2CH2CH2CH3). 13C NMR (125 MHz, DMSO-d6):
d 172.23,
154.12 (NCO), 144.65, 136.62, 130.17, 130.05, 127.46, 125.54,
122.01, 118.95, 118.42, 111.56, 111.48, 106.24, 52.40 (C5),
46.63 (C11a), 37.80, 29.67, 22.46, 19.33, 13.46 ppm (CH3).
IR: 3321.19 (–NH–), 1765.08, 1696.47 cmꢁ1 (–CO–). HPLC/MS
(ESI): Purity 97.62%, for C21H20BrN3O2S: m/z (%): 459 [Mþþ2],
457 [Mþ], 242 (100%).
(5S,11aR) 5-(5-Bromo-2-thienyl)-2-tert-butyl-5,6,11,11a-
tetrahydro-1H-imidazo[10,5 0:1,6]pyrido[3,4-b]indole-
1,3(2H)-dione (13)
Yellow powder (0.23 g, 50%): Rf ¼ 0.42 (CH2Cl2); mp: 196–1998C;
1H NMR (500 MHz, DMSO-d6): d 10.88 (s, 1H, NH), 7.56–7.53
(m, 1H, Ar), 7.29 (dt, J ¼ 8.2, 1.0 Hz, 1H, Ar), 7.12–7.06 (m, 3H,
Ar), 7.01 (ddd, J ¼ 8.0, 7.1, 1.1 Hz, 1H, Ar), 6.17 (s, 1H, NCHCS),
4.36 (dd, J ¼ 11.4, 4.2 Hz, 1H, CHC(O)N), 3.23 (dd, J ¼ 14.9, 4.3 Hz,
(5R,11aR) 5-(5-Bromo-2-thienyl)-2-butyl-5,6,11,11a-
tetrahydro-1H-imidazo[10,5 0:1,6]pyrido[3,4-b]indole-
1,3(2H)-dione (10)
Yellow powder (0.26 g, 57.6%): Rf ¼ 0.62 (CH2Cl2); mp: 100–
1028C; 1H NMR (500 MHz, DMSO-d6): d 11.11 (s, 1H, NH), 7.56–
7.53 (m, 1H, Ar), 7.36–7.31 (m, 1H, Ar), 7.15–7.11 (m, 2H, Ar), 7.06–
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