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Arch. Pharm. Chem. Life Sci. 2011, 11, 149–157
(Mþ þ 2), m/z 417 (Mþ; 100%); anal. calcd. (C21H18Cl2N2O3): C,
1H, Ar), 7.18–7.19 (d, 1H, Ar), 7.61–7.60 (d, 1H, Ar), 6.21 (s,
1H, CHPh), 4.33–4.28 (dd, 1H, CHC(O)N), 4.13–4.07 (d,
1H, CHaHbC(O)N), 3.95–3.89 (d, 1H, CHaHbC(O)N), 3.83–3.76 (dd,
1H, CHaHb), 3.73–3.66 (q, 2H, NCH2), 3.27–3.17 (m, 1H, CHaHb),
1.23–1.18 (t, 3H, CH3); 13C-NMR: 67.1, 165.7, 139.8, 136.6, 132.6,
133.5, 132.1, 128.8, 128.5, 125.1, 126.1, 122.6, 120.2, 118.6, 111.2,
106.9, 56.2 (C6), 49.6 (C12a), 41.2, 29.5, 23.7, 12.1; IR (cmꢃ1): 3208,
1657, 1650; MS (EI): m/z 396 (Mþ þ 2), m/z 394 (Mþ; 100%); anal.
calcd. (C22H20ClN3O2): C, 67.09; H, 5.12; N, 10.67. Found: C, 67.29;
H, 5.24; N, 10.50.
60.44; H, 4.35; N, 6.71. Found: C, 60.11; H, 4.26; N, 6.81.
Methyl (1S,3R)-1-(4-chlorophenyl)-2-(chloroacetyl)-
2,3,4,9-tetrahydro-1H-b-carboline-3-carboxylate (XVIII)
Green powder (2.31 g, 97%); m.p.: 110–1128C; Rf ¼ 0.66 (CH2Cl2/
MeOH, 98:2); 1H-NMR (CDCl3): 7.72 (brs, 1H, NH), 7.55–7.53 (d, 2H,
Ar), 7.29–7.27 (d, 2H, Ar), 7.24–7.11 (m, 4H, Ar), 6.10 (s, 1H, CHPh),
5.23–5.20 (d, 1H, CHCOOCH3), 4.13–4.09 (d, 1H, COCHaHbCl),
4.04–4.00 (d, 1H, COCHaHbCl), 3.65 (s, 3H, OCH3), 3.14–3.06
(dd, 1H, CHaCHb), 2.90–2.56 (d, 1H, CHaHb); IR (cmꢃ1): 3319,
1737, 1658; MS (EI): m/z 421 (Mþ þ 4), m/z 419 (Mþ þ 2),
m/z 417 (Mþ; 100%); anal. calcd. (C21H18Cl2N2O3): C, 60.44; H,
4.35; N, 6.71. Found: C, 60.72; H, 4.45; N, 6.85.
(6S,12aR)-2-Ethyl-6-(4-chlorophenyl)-2,3,6,7,12,12a-
hexahydropyrazino[1’,2’:1,6]pyrido[3,4-b]indole-1,4-dione
(XXII)
Buff powder (0.14 g, 25%); m.p.: 255–2588C; Rf ¼ 0.53 (CH2Cl2/
MeOH, 97:3); 1H-NMR (CDCl3): 7.98 (brs, 1H, NH), 7.64–7.62 (d, 2H,
Ar), 7.47–7.45 (d, 2H, Ar), 7.25–7.23 (d, 1H, Ar), 7.19–7.15 (m, 3H,
Ar), 6.22 (s, 1H, CHPh), 4.33–4.28 (dd, 1H, CHC(O)N), 4.13–4.07 (d,
1H, CHaHbC(O)N), 3.94–3.86 (d, 1H, CHaHbC(O)N), 3.82–3.75 (dd,
1H, CHaHb), 3.42–3.35 (q, 2H, NCH2), 3.27–3.17 (m, 1H, CHaHb),
1.23–1.18 (t, 3H, CH3); 13C-NMR: 167.2, 165.8, 139.8, 136.6, 133.6,
132.2, 128.8, 128.6, 126.1, 125.9, 122.7, 120.2, 118.6, 111.3, 106.9,
55.3 (C6), 48.4 (C12a), 41.2, 29.5, 23.7, 12.1; IR (cmꢃ1): 3279, 1658,
1652; MS (EI): m/z 396 (Mþ þ 2), m/z 394 (Mþ; 100%); anal. calcd.
(C22H20ClN3O2): C, 67.09; H, 5.12; N, 10.67. Found: C, 66.99; H,
5.01; N, 10.47.
Methyl (1S, 3S)-1-(4- chlorophenyl)-2-(chloroacetyl)- 2, 3,
4, 9-tetrahydro-1H-b-carboline-3-carboxylate (XIX)
Yellow (2.25, 95%); m.p.: 228–2328C; Rf ¼ 0.76 (CH2Cl2/MeOH,
98:2); 1H-NMR (CDCl3): 10.86 (brs, 1H, NH), 7.57–7.55 (d, 2H,
Ar), 7.39–7.36 (d, 2H, Ar), 7.31–7.29 (d, 1H, Ar), 7.13–7.00 (m,
3H, Ar), 6.82 (s, 1H, CHPh), 5.24–5.22 (d, 1H, CHCOOCH3), 4.45–
4.41 (d, 1H, COCHaHbCl), 4.38–4.34 (d, 1H, COCHaHbCl), 3.29 (s,
3H, OCH3), 3.13–3.06 (dd, 1H, CHaCHb), 2.96–2.49 (d, 1H, CHaHb);
IR (cmꢃ1): 3246, 1730, 1658; MS (EI): m/z 421 (Mþ þ 4), m/z 419
(Mþ þ 2), m/z 417 (Mþ; 100%); anal. calcd. (C21H18Cl2N2O3): C,
60.44; H, 4.35; N, 6.71. Found: C, 60.46; H, 4.47; N, 6.88.
(6S,12aS)-2-Ethyl-6-(4-chlorophenyl)-2,3,6,7,12,12a-
hexahydropyrazino[1’,2’:1,6]pyrido[3,4-b]indole-1,4-dione
(XXIII)
Methyl (1R,3S)-1-(4-chlorophenyl)-2-(chloroacetyl)-
2,3,4,9-tetrahydro-1H-b-carboline-3-carboxylate (XX)
Yellowish green powder (2.19 g, 92%); m.p.: 107–1108C; Rf ¼ 0.67
1
(CH2Cl2/MeOH, 98:2); H-NMR (CDCl3): 10.86 (brs, 1H, NH), 7.57–
Golden yellow powder (0.16 g, 30%); m.p.: 300–3038C; Rf ¼ 0.5
(CH2Cl2/MeOH, 97:3); 1H-NMR (CDCl3): 7.91 (brs, 1H, NH), 7.64–7.61
(d, 2H, Ar), 7.30–7.29 (d, 2H, Ar), 7.25–7.15 (m, 4H, Ar), 6.22 (s,
1H, CHPh), 4.34–4.29 (dd, 1H, CHC(O)N), 4.14–4.08 (d,
1H, CHaHbC(O)N), 3.95–3.89 (d, 1H, CHaHbC(O)N), 3.83–3.76 (dd,
1H, CHaHb), 3.73–3.66 (q, 2H, NCH2), 3.27–3.18 (m, 1H, CHaHb),
1.23–1.18 (t, 3H, CH3); IR (cmꢃ1): 3281, 1658, 1643; MS (EI): m/z 396
(Mþ þ 2), m/z 394 (Mþ; 100%); anal. calcd. (C22H20ClN3O2): C, 67.09;
H, 5.12; N, 10.67. Found: C, 67.09; H, 5.00; N, 10.47.
7.55 (d, 2H, Ar), 7.13–7.00 (m, 6H, Ar), 6.92 (s, 1H, CHPh), 5.20–5.16
(d, 1H, CHCOOCH3), 4.48–4.44 (d, 1H, COCHaHbCl), 3.98–3.94 (d,
1H, COCHaHbCl), 3.29 (s, 3H, OCH3), 3.13–3.06 (dd, 1H, CHaCHb),
2.98–2.47 (d, 1H, CHaHb); IR (cmꢃ1): 3326, 1727, 1650, MS (EI):
m/z 421 (Mþ þ 4;), m/z 419 (Mþ þ 2), m/z 417 (Mþ; 100%), anal.
calcd. (C21H18Cl2N2O3): C, 60.44; H, 4.35; N, 6.71. Found: C, 60.79;
H, 4.65; N, 6.92.
General procedures for the preparation of 2-ethyl or tert-
butyl-6-(4-chlorophenyl)-2,3,6,7,12,12a-
(6R,12aS)-2-Ethyl-6-(4-chlorophenyl)-2,3,6,7,12,12a-
hexahydropyrazino[1’,2’:1,6]pyrido[3,4-b]indole-1,4-dione
(XXIV)
hexahydropyrazino[1’,2’:1,6]pyrido[3,4-b]indole-1,4-dione
A solution of the of the appropriate chloroacetyl derivative XVII–
XX (0.58 g, 1.4 mmol) and the appropriate amine (2.8 mmol) in
methanol (25 mL) was heated to reflux under a nitrogen atmos-
phere for 16 h. The reaction mixture was cooled to room
temperature and evaporated to dryness under reduced pressure.
The residue was dissolved in CH2Cl2, and the organic layer was
washed with water, dried over Na2SO4, filtered, and concentrated
to dryness. The crude product was then purified using column
chromatography eluting with CH2Cl2/CH3OH (99:1). The product
was crystallized from ethanol.
Yellow powder (0.14 g, 25%); m.p.: 257–2598C; Rf ¼ 0.51 (CH2Cl2/
MeOH, 97:3); 1H-NMR (CDCl3): 7.85 (brs, 1H, NH), 7.64–7.62 (d, 2H,
Ar), 7.79–7.72 (d, 2H, Ar), 7.59–7.40(dd, 1H, Ar), 7.25–7.24 (d, 1H,
Ar), 7.21–7.17 (m, 2H, Ar), 6.21 (s, 1H, CHPh), 4.35–4.29 (dd,
1H, CHC(O)N), 4.14–4.08 (d, 1H, CHaHbC(O)N), 3.95–3.90 (d, 1H,
CHaHbC(O)N), 3.83–3.76 (dd, 1H, CHaHb), 3.73–3.66 (q, 2H, NCH2),
3.27–3.18 (m, 1H, CHaHb), 1.23–1.18 (t, 3H, CH3); IR (cmꢃ1): 3190,
1657, 1631; MS (EI): m/z 396 (Mþ þ 2), m/z 394 (Mþ; 100%); anal.
calcd. (C22H20ClN3O2): C, 67.09; H, 5.12; N, 10.67. Found: C, 67.19;
H, 4.99; N, 10.64.
(6R,12aR)-2-Ethyl-6-(4-chlorophenyl)-2,3,6,7,12,12a-
hexahydropyrazino[1’,2’:1,6]pyrido[3,4-b]indole-1,4-dione
(XXI)
Buff crystals (0.22 g, 40%); m.p.: 300–3038C; Rf ¼ 0.5 (CH2Cl2/
MeOH, 97:3); 1H-NMR (CDCl3): 8.03 (brs, 1H, NH), 7.64–7.62 (d,
2H, Ar), 7.29–7.30 (d, 2H, Ar), 7.24–7.22 (d, 1H, Ar), 7.21–7.19 (d,
(6R,12aR)-2-tert-Butyl-6-(4-chlorophenyl)-2,3,6,7,12,12a-
hexahydropyrazino[1’,2’:1,6]pyrido[3,4-b]indole-1,4-dione
(XXV)
White powder (0.05 g, 10%); m.p.: 230–2328C; Rf ¼ 0.13 (CH2Cl2/
MeOH, 97:3); 1H-NMR (CDCl3): 7.88 (brs, 1H, NH), 7.60–7.56 (d, 2H,
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