September 2007
1305
dione (6aa) and 3-(1H-Indol-3-yl)-4-(1H-pyrrol-2-yl)-1-phenyl-1H-pyr-
role-2,5-dione (6ab) Compound 5a (0.2 mmol) was heated with ammo-
nium acetate (40 mmol) for 1 h at 150 °C (bath temperature). The mixture
was cooled and extracted with ethyl acetate after the addition of water. The
organic layer was washed with brine, dried over Na2SO4 and concentrated in
vacuo. The residue was purified by chromatography on silica gel using pe-
troleum ether/ethyl acetate as eluent to yield 6aa and 6ab, respectively as a
red power.
7.44 (1H, d, Jꢂ8.0 Hz), 7.83 (1H, d, Jꢂ2.4 Hz, 2-Hindole), 11.06 (1H, s, 1-
Hpyrrole), 11.94 (1H, s, 1-Hindole); Anal. Calcd for C17H12BrN3O2: C, 55.15; H,
3.27; N, 11.35. Found: C, 55.26; H, 3.17; N, 11.47.
3-[5-Methoxy-(1H-indol-3-yl)]-4-(1H-pyrrol-2-yl)-1-methyl-1H-pyrrole-
2,5-dione (6cc): Yield 79%; MS m/z: 322 (Mꢅ); mp 227—228 °C; 1H-NMR
(DMSO-d6) d: 3.02 (3H, s, CH3), 3.42 (3H, s, OCH3), 6.13—6.15 (1H, m,
Hpyrrole), 6.25—6.27 (2H, m,), 6.74 (1H, dd, Jꢂ2.0, 8.4 Hz), 6.95—6.97 (3H,
m), 7.35 (1H, d, Jꢂ8.4 Hz), 7.79 (1H, d, Jꢂ2.4 Hz, 2-Hindole), 11.06 (1H, s,
1-Hpyrrole), 11.69 (1H, s, 1-Hindole); Anal. Calcd for C18H15N3O3: C, 67.28; H,
4.71; N, 13.08. Found: C, 67.20; H, 4.62; N, 13.21.
3-[6-Bromo-(1H-indol-3-yl)]-4-(1H-pyrrol-2-yl)-1-methyl-1H-pyrrole-
2,5-dione (6dc): Yield 83%; MS m/z: 371 (Mꢅ); mp 197—199 °C; 1H-NMR
(DMSO-d6) d: 3.02 (3H, s, CH3), 6.15—6.17 (1H, m, Hpyrrole), 6.37—6.40
(1H, m, Hpyrrole), 7.14—7.18 (2H, m), 7.45 (1H, d, Jꢂ8.0), 7.59 (1H, s), 8.10
(1H, d, Jꢂ2.0, 2-Hindole), 11.10 (1H, s, 1-Hpyrrole), 12.02 (1H, s, 1-Hindole);
Anal. Calcd for C17H12BrN3O2: C, 55.15; H, 3.27; N, 11.35. Found: C,
55.23; H, 3.35; N, 11.50.
Production of 6ad, 6bd, 6cd and 6dd The same procedure as described
above afforded compounds 6ad, 6bd, 6cd and 6dd, respectively from 5a—d
and 32% ethylamine in methanol after purification by chromatography on
silica gel using petroleum ether/ethyl acetate as eluent.
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6aa: Yield 39%; mp ꢃ250 °C; MS m/z: 278 (Mꢅ); H-NMR (DMSO-d6)
d: 6.07—6.09 (1H, m, Hpyrrole), 6.23—6.25 (1H, m, Hpyrrole), 6.86—6.95 (3H,
m, Hphenyl), 7.13 (1H, t, Jꢂ8.0 Hz), 7.47 (1H, d, Jꢂ8.0 Hz), 7.51 (1H, d,
Jꢂ3.2 Hz), 10.92 (1H, s, N-H), 11.00 (1H, s, 1-Hpyrrole), 11.75 (1H, s, 1-
Hindole); Anal. Calcd for C16H11N3O2: C, 69.31; H, 4.00; N, 15.15. Found:
C, 69.40; H, 4.09; N, 15.06.
6ab: Yield 42%; mp 203 °C; MS m/z: 354 (Mꢅ); 1H-NMR (DMSO-d6) d:
6.12—6.14 (1H, m, Hpyrrole), 6.37 (1H, br, Hpyrrole), 6.94 (2H, d, Jꢂ7.2 Hz),
6.99 (1H, s), 7.13—7.17 (1H, m), 7.34—7.54 (6H, m), 7.85 (1H, d,
Jꢂ2.8 Hz, 2-Hindole), 11.10 (1H, s, 1-Hpyrrole), 11.82 (1H, s, 1-Hindole); Anal.
Calcd for C22H15N3O2: C, 74.78; H, 4.28; N, 11.89. Found: C, 74.70; H,
4.19; N, 11.76.
Production of 3-[5-Bromo-(1H-indol-3-yl)]-4-(1H-pyrrol-2-yl)-1H-
pyrrole-2,5-dione (6ba) and 3-[5-Bromo-(1H-indol-3-yl)]-4-(1H-pyrrol-
2-yl)-1-phenyl-1H-pyrrole-2,5-dione (6bb) The same procedure as de-
scribed above afforded compounds 6ba and 6bb, respectively from 5b after
purification by chromatography on silica gel using petroleum ether/ethyl
acetate as eluent.
3-(1H-indol-3-yl)-4-(1H-pyrrol-2-yl)-1-ethyl-1H-pyrrole-2,5-dione (6ad):
1
Yield 87%; MS m/z: 306 (Mꢅ); mp 197—198 °C; H-NMR (DMSO-d6) d:
1.18 (3H, t, Jꢂ7.2, CH3), 3.55—3.60 (2H, m, CH2), 6.09—6.11 (1H, m,
Hpyrrole), 6.29 (1H, br, Hpyrrole), 6.86 (1H, d, Jꢂ8.0 Hz), 6.91 (1H, t,
Jꢂ8.0 Hz), 6.96 (1H, s), 7.14 (1H, t, Jꢂ8.0 Hz), 7.48 (1H, d, Jꢂ8.0 Hz),
7.80 (1H, d, Jꢂ2.4 Hz, 2-Hindole), 11.04 (1H, s, 1-Hpyrrole), 11.78 (1H, s, 1-
Hindole); Anal. Calcd for C18H15N3O2: C, 70.81; H, 4.95; N, 13.76. Found: C,
70.94; H, 4.87; N, 13.70.
1
6ba: Yield 48%; mp ꢃ250 °C; MS m/z: 357(Mꢅ); H-NMR (DMSO-d6)
d: 6.12—6.14 (1H, m, Hpyrrole), 6.27—6.29 (1H, m, Hpyrrole), 6.96—6.98 (2H,
m), 7.24 (1H, dd, Jꢂ2.4, 8.4 Hz), 7.44 (1H, d, Jꢂ8.4 Hz), 7.82 (1H, d,
Jꢂ2.4 Hz, 2-Hindole), 10.96 (1H, s, N-H), 11.05 (1H, s, 1-Hpyrrole), 11.92 (1H,
s, 1-Hindole); Anal. Calcd for C16H10BrN3O2: C, 53.95; H, 2.83; N, 11.80.
Found: C, 53.89; H, 2.90; N, 11.69.
3-[5-Bromo-(1H-indol-3-yl)]-4-(1H-pyrrol-2-yl)-1-ethyl-1H-pyrrole-2,5-
dione (6bd): Yield 77%; MS m/z: 385 (Mꢅ); mp 187—190 °C; 1H-NMR
(DMSO-d6) d: 1.17 (3H, t, Jꢂ7.2 Hz, CH3), 3.54—3.60 (2H, m, CH2),
6.14—6.16 (1H, m, Hpyrrole), 6.32—6.39 (1H, m, Hpyrrole), 6.98—7.00 (2H,
m), 7.25 (1H, dd, Jꢂ2.4, 8.8 Hz), 7.45 (1H, d, Jꢂ8.8 Hz), 7.86 (1H, d,
Jꢂ4 Hz, 2-Hindole), 11.07 (1H, s, 1-Hpyrrole), 11.95 (1H, s, 1-Hindole); Anal.
Calcd for C18H14BrN3O2: C, 56.27; H, 3.67; N, 10.94. Found: C, 56.36; H,
3.57; N, 10.82.
3-[5-Methoxy-(1H-indol-3-yl)]-4-(1H-pyrrol-2-yl)-1-ethyl-1H-pyrrole-
2,5-dione (6cd): Yield 80%; MS m/z: 336 (Mꢅ); mp 190—193 °C; 1H-NMR
(DMSO-d6) d: 1.17 (3H, t, Jꢂ7.2 Hz, CH3), 3.42 (3H, s, OCH3), 3.54—3.59
(2H, m, CH2), 6.13—6.15 (1H, m, Hpyrrole), 6.24 (1H, d, Jꢂ2.4 Hz), 6.26—
6.28 (1H, m, Hpyrrole), 6.74 (1H, dd, Jꢂ2.8, 8.8 Hz), 6.95—6.97 (1H, m),
7.35 (1H, d, Jꢂ8.8 Hz), 7.81 (1H, d, Jꢂ3.2 Hz, 2-Hindole), 11.05 (1H, s, 1-
Hpyrrole), 11.69 (1H, s, 1-Hindole); Anal. Calcd for C19H17N3O3: C, 68.05; H,
5.11; N, 12.53. Found: C, 68.13; H, 5,03; N, 12.40.
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6bb: Yield 40%; mp ꢃ250 °C; MS m/z: 433 (Mꢅ); H-NMR (DMSO-d6)
d: 6.17—6.19 (1H, m, Hpyrrole), 6.41 (1H, br, Hpyrrole), 7.03 (1H, s), 7.08 (1H,
s), 7.27 (1H, dd, Jꢂ1.2, 8.4 Hz), 7.15—7.54 (6H, m), 7.89 (1H, d, Jꢂ2.8 Hz,
2-Hindole), 11.14 (1H, s, 1-Hpyrrole), 11.98 (1H, s, 1-Hindole); Anal. Calcd for
C22H14BrN3O2: C, 61.13; H, 3.26; N, 9.72. Found: C, 61.05; H, 3.37; N,
9.86.
Production of 3-[5-Methoxy-(1H-indol-3-yl)]-4-(1H-pyrrol-2-yl)-1H-
pyrrole-2,5-dione (6ca) and 3-[5-Methoxy-(1H-indol-3-yl)]-4-(1H-pyrrol-
2-yl)-1-phenyl-1H-pyrrole-2,5-dione (6cb) The same procedure as de-
scribed above afforded compounds 6ca and 6cb, respectively from 5c after
purification by chromatography on silica gel using petroleum ether/ethyl
acetate as eluent.
1
6ca: Yield 45%; mp ꢃ250 °C; MS m/z: 308 (Mꢅ); H-NMR (DMSO-d6)
d: 3.41 (3H, s, OCH3), 6.10—6.12 (1H, m, Hpyrrole), 6.21—6.23 (1H, m,
3-[6-Bromo-(1H-indol-3-yl)]-4-(1H-pyrrol-2-yl)-1-ethyl-1H-pyrrole-2,5-
dione (6dd): Yield 81%; MS m/z: 385 (Mꢅ); mp 183—185 °C; 1H-NMR
(DMSO-d6) d: 1.17 (3H, t, Jꢂ7.6 Hz, CH3), 3.55—3.60 (2H, m, CH2),
6.14—6.16 (1H, m, Hpyrrole), 6.36—6.38 (1H, m, Hpyrrole), 7.13—7.16 (2H,
m), 7.40 (1H, d, Jꢂ8.4), 7.57 (1H, s), 8.03 (1H, d, Jꢂ2.0, 2-Hindole), 11.10
(1H, s, 1-Hpyrrole), 12.00 (1H, s, 1-Hindole); Anal. Calcd for C18H14BrN3O2: C,
56.27; H, 3.67; N, 10.94. Found: C, 56.20; H, 3.74; N, 11.03.
Production of 7a and 7b 32% methylamine in methanol (3 ml) was
added to compound 3a or 3b (0.2 mmol) and the mixture was stirred for 2—
3 h at ꢀ5—0 °C. The solvent was removed in vacuo and the residue was re-
crystallized from ethyl acetate to afford compound 7a or 7b.
4-Chloro-3-(1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione (7a): Yield
79%; mp 202—202 °C; 1H-NMR (DMSO-d6) d: 3.01 (3H, s, CH3), 7.17
(1H, t, Jꢂ8.0 Hz, Hphenyl), 7.24 (1H, t, Jꢂ8.0 Hz, Hphenyl), 7.52 (1H, d,
Jꢂ8.0 Hz, Hphenyl), 7.93 (1H, d, Jꢂ8.0 Hz, Hphenyl), 8.13 (1H, d, Jꢂ2.8 Hz, 2-
Hindole), 12.16 (1H, s, 1-Hindole); Anal. Calcd for C13H9ClN2O2: C, 59.90; H,
3.48; N, 10.75. Found: C, 59.81; H, 3.57; N, 10.82.
4-Chloro-3-[5-bromo-(1H-indol-3-yl)]-1-methyl-1H-pyrrole-2,5-dione
(7b): Yield 75%; mp 230—231 °C (dec.); 1H-NMR (DMSO-d6) d: 3.01 (3H,
s, CH3), 7.35 (1H, dd, Jꢂ2.0, 8.8 Hz, 6-Hphenyl), 7.49 (1H, d, Jꢂ8.8 Hz,
Hpyrrole), 6.72 (1H, dd, Jꢂ2.4, 8.4 Hz), 6.94—6.96 (2H, m), 7.36 (1H, d,
Jꢂ8.4 Hz), 7.54 (1H, d, Jꢂ2.0 Hz, 2-Hindole), 10.90 (1H, s, N-H), 11.03 (1H,
s, 1-Hpyrrole), 11.67 (s, 1H, 1-Hindole); Anal. Calcd for C17H13N3O3: C, 66.44;
H, 4.26; N, 13.67. Found: C, 66.51; H, 4.20; N, 13.54.
6cb: Yield 40%; mp 202 °C; MS m/z: 384 (Mꢅ); 1H-NMR (DMSO-d6) d:
3.44 (3H, s, OCH3), 6.17—6.19 (1H, m, Hpyrrole), 6.25 (1H, t, Jꢂ2.4 Hz),
6.32 (1H, d, Jꢂ2.8 Hz,), 6.34—6.36 (1H, m, Hpyrrole), 6.76 (1H, dd,
Jꢂ2.4 Hz, 8.8), 6.99—7.01 (1H, m), 7.06 (1H, t, Jꢂ2.4 Hz), 7.32—7.55
(4H, m), 7.85 (1H, d, Jꢂ2.8 Hz, 2-Hindole), 11.29 (1H, s, 1-Hpyrrole), 11.74
(1H, s, 1-Hindole); Anal. Calcd for C23H17N3O3: C, 72.05; H, 4.47; N, 10.96.
Found: C, 72.17; H, 4.59; N, 10.87.
Production of 6ac, 6bc, 6cc and 6dc. General Procedure 32% methyl-
amine in methanol (3 ml) was added to compounds 5a—d (0.1 mmol) re-
spectively and the mixture was stirred for 1—2 h at room temperature. The
solvent was removed in vacuo and the residue was purified by chromatogra-
phy on silica gel using petroleum ether/ethyl acetate as eluent to afford com-
pounds 6ac, 6bc, 6cc and 6dc, respectively.
3-(1H-Indol-3-yl)-4-(1H-pyrrol-2-yl)-1-methyl-1H-pyrrole-2,5-dione
1
(6ac): Yield 88%. MS m/z: 292 (Mꢅ); mp 222—224 °C; H-NMR (DMSO-
d6) d: 3.01 (3H, s, CH3), 6.09—6.11 (1H, m, Hpyrrole), 6.29 (1H, br, Hpyrrole),
6.86—6.96 (3H, m), 7.14 (1H, t, Jꢂ8.0 Hz), 7.48 (1H, d, Jꢂ8.0 Hz), 7.78
(1H, d, Jꢂ2.8 Hz, 2-Hindole), 11.02 (1H, s, 1-Hpyrrole), 11.77 (1H, s, 1-Hindole);
Anal. Calcd for C17H13N3O2: C, 70.09; H, 4.50; N, 14.42. Found: C, 70.16;
H, 4.37; N, 14.54.
H
phenyl), 8.12 (1H, d, Jꢂ2.0 Hz, Hphenyl), 8.14 (1H, d, Jꢂ2.8 Hz, 2-Hindole),
12.32 (1H, s, 1-Hindole); Anal. Calcd for C13H8BrClN2O2: C, 45.98; H, 2.37;
N, 8.25. Found: C, 45.87; H, 2.46; N, 8.37.
Production of 8a and 8b The same procedure was performed as com-
pounds 4a—d to afford 8a or 8b from 7a or 7b.
3-[5-Bromo-(1H-indol-3-yl)]-4-(1H-pyrrol-2-yl)-1-methyl-1H-pyrrole-
2,5-dione (6bc): Yield 81%; MS m/z: 371 (Mꢅ); mp 219—220 °C (dec.); 1H-
NMR (DMSO-d6) d: 3.01 (3H, s, CH3), 6.13—6.16 (1H, m, Hpyrrole), 6.33—
6.35 (1H, m, Hpyrrole), 6.98—7.00 (2H, m), 7.25 (1H, dd, Jꢂ2.0, 8.0 Hz),
4-Chloro-3-[1-(tert-butyloxycarbonyl)-1H-indol-3-yl]-1-methyl-1H-pyr-
1
role-2,5-dione (8a): Yield 77%; mp 161—163 °C; H-NMR (DMSO-d6) d:
1.66 (9H, s, C(CH3)3), 2.97 (3H, s, CH3), 7.34 (1H, t, Jꢂ7.2 Hz, Hphenyl),
7.41 (1H, t, Jꢂ7.2 Hz, Hphenyl), 7.95 (1H, d, Jꢂ7.2 Hz, Hphenyl), 8.10 (1H, s,