reduced pressure and the crude residue was dissolved in EtOAc,
and washed with H2O and brine. The organic layer was dried
with anhydrous Na2SO4 then concentrated in vacuo. The residue
was purified by flash column chromatography on silica gel
(hexane:EtOAc 90:10 to 80:20), to furnish the desired alkylated
compounds 19 in 71% yield (spectroscopy was described above)
and 20.
25.9, 13.8; MS (EI) m/z 214 (M+, 100%). C13H14N2O (214.11) calc.
C(72.87), H(6.59), N(13.07); found. C(71.33), H(6.74), N(11.99).
5-Ethyl-2,3,5,6-tetra◦hydroazepino[4,5-b]indol-4(1H)-one (24).
White solid M.p. 236 C, yield 83%. IR (KBr cm-1) 3227, 3075,
2969, 2888, 1658, 1458; 1H-NMR (300 MHz, DMSO-d6) d/ppm:
1.02 (t, J = 7.2 Hz, 3H), 1.89–2.10 (m, 2H), 2.72–2.85 (m, 2H),
3.50 (m, plus large overlapping H2O peak), 3.82 (t, J = 6.9 Hz,
1H), 6.94 (dt, J = 7.8 Hz, J = 1.2 Hz, 1H), 7.03 (dt, J = 8.1 Hz,
J = 1.2 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 7.5 Hz,
Diethyl 2-(3-(2-(tert-butoxycarbonylamino)ethyl)-1H-indol-2-
yl)-2-benzylmalonate (20). Yellow oil, yield 86%. IR (film cm-1)
1
3420, 2977, 2935, 1724, 1578, 1502, 1454; H-NMR (300 MHz,
=
1H), 7.71 (brt, J = 6.6 Hz, 1H, NHC O), 10.6 (s, 1H, NH);
13C-NMR (75 MHz, DMSO-d6) d/ppm: 173.7, 135.0, 131.1,
128.3, 120.9, 118.5, 117.5, 110.8, 108.1, 46.5, 38.7, 25.8, 24.1,
12.9; MS (EI) m/z 228 (M+, 100%). C14H16N2O (228.13) calc.
C(73.66), H(7.06), N(12.28) found. C(73.28), H(7.12), N(11.88).
CDCl3) d/ppm: 1.25 (t, J = 6.9 Hz, 6H), 1.43 (s, 9H), 2.95–3.00
(m, 2H), 3.36–3.43 (m, 2H), 3.66 (s, 2H), 4.08–4.40 (m, 4H),
4.65 (brs, 1H, -NHBoc), 6.64–6.67 (m, 2H), 7.00–7.20 (m, 6H),
7.68–7.71 (m, 1H), 10.02 (brs, 1H, NH); 13C-NMR (75 MHz,
CDCl3) d/ppm: 169.6, 155.8, 135.1, 134.2, 129.5, 129.46, 128.1,
128.0, 127.2, 121.9, 119.3, 119.1, 111.3, 109.4, 79.0, 62.2, 58.9,
43.6, 40.5, 28.4, 25.2, 14.0; MS (EI) m/z 508 (M+, 20%), 91
(M+ - 417, 100%).
5-(2-Hydroxyethyl)-2,3,5,6-tetrahydroazepino[4,5-b]indol-4(1H)-
◦
one (25). White solid M.p. 210 C, yield 93%. IR (KBr cm-1)
1
3394, 3333, 3214, 3098, 2950, 2889, 1646, 1459, 1426; H-NMR
(300 MHz, DMSO-d6) d/ppm: 2.05–2.26 (m, 2H), 2.78–2.82 (m,
2H), 3.4–3.7 (m, 4H), 4.18–4.164 (m, 1H), 4.64 (t, J = 5.5 Hz,
1H, OH), 6.95 (dt, J = 7.8 Hz, J = 0.9 Hz, 1H), 7.03 (dt, J =
8.1 Hz, J = 1.2 Hz, 1H), 7.29–7.35 (m, 2H), 7.73 (brt, J = 6.3 Hz,
Experimental procedure for the preparation of
azepino[4,5-b]indolone derivatives
1H, NHC O), 10.6 (s, 1H, NH); 13C-NMR (75 MHz, DMSO-d6)
To a solution of the corresponding C-2 alkylated tryptamine
derivatives 5, 14–20 (1.0 mmol) in dry CH2Cl2 (10 mL) trifluo-
roacetic acid (3.0 mL, 39 mmol) was added. The solution was
stirred at room temperature for 1 h. After the consumption of
the starting material, as shown by TLC, the solvent and the
remaining TFA were removed under reduced pressure and the
crude residue was dissolved in dry methanol (10 mL) and K2CO3
(1.2 g, 9.0 mmol) was added. The suspension was stirred at room
temperature. After the consumption of the starting material, as
shown by TLC, the solvent was removed under reduced pressure
and the crude residue was dissolved in EtOAc and washed with
H2O and brine. The organic layer was dried with anhydrous
Na2SO4 then concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel (EtOAc:hexane 80:20
to EtOAc), to furnish the desired azepinoindolones 1, 23–26, 28
and 29.
=
d/ppm: 173.6, 134.9, 130.6, 128.3, 120.7, 118.5, 117.3, 110.9,
108.0, 59.2, 39.8, 38.6, 32.7, 25.8; MS (EI) m/z 244 (M+, 100%).
C14H16N2O2 (244.12) calc. C(68.83), H(6.60), N(11.47) found
C(68.44), H(6.59), N(11.12).
5-(2-Hydroxypropyl)-2,3,5,6-tetrahydroazepino[4,5-b]indol-4(1H)-
one (26, mixture of diastereomers). White solid M.p. 90 ◦C,
yield 50%. IR (KBr cm-1) 3357, 3304, 3059, 2965, 2924, 1651,
1459; 1H-NMR (300 MHz, DMSO-d6) d/ppm: 1.15–1.20 (m,
CH3-CH(OH)), 1.86–2.20 (m, CH2-CH(OH)CH3), 2.80–2.81 (m,
=
C1-H2), 3.40–3.60 (m, CH2-NH-C O and C5-H), 4.29–4.33 (m,
CH(OH)CH3), 4.60 (d, J = 5.1 Hz, OH), 4.66 (d, J = 5.1 Hz,
OH), 6.92–7.06 (m, Ar-H), 7.28–7.35 (m, Ar-H), 7.70–7.75 (m,
NHC O), 10.54 (s, NH), 10.59 (s, NH); 13C-NMR (75 MHz,
=
DMSO-d6) d/ppm: 174.1+ 173.6, 135.0 + 134.9, 130.8 + 130.7,
128.4 + 128.3, 120.8 + 120.6, 118.5, 117.4 + 117.2, 110.9 + 110.8,
108.1 + 107.7, 64.2, 41.3, 38.8, 38.5, 38.1, 25.9 + 25.8, 24.5 +
23.5; MS (EI) m/z 258 (M+, 100%). C15H18N2O2 (258.14) calc.
C(69.74), H(7.02), N(10.84) found. C(68.02), H(7.28), N(9.73).
2,3,5,6-Tetrahydroazepino[4,5-b]indol-4(1H)-one (1). Brown
◦
solid M.p. 225 C (dec.) (lit.8 >230 ◦C (dec.)), yield 75%. IR
(KBr cm-1) 3293, 3241, 3078, 2971, 2938, 2886, 1732, 1655, 1465;
1H-NMR (300 MHz, DMSO-d6) d/ppm: 2.74–2.77 (m, 2H), 3.50–
3.56 (m, 2H), 3.77 (s, 2H), 6.94 (dt, J = 8.1 Hz, J = 1.2 Hz, 1H),
7.02 (dt, J = 8.0 Hz, J = 1.2 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.34
(d, J = 7.8 Hz, 1H), 7.75 (brt, J = 6.7 Hz, 1H, NHC= 0), 10.77 (s,
1H, NH); 13C-NMR (75 MHz, DMSO-d6) d/ppm: 172.3, 134.7,
128.3, 126.9, 120.7, 118.4, 117.3, 110.5, 108.0, 39.2, 35.0, 25.6;
MS (EI) m/z 200 (M+, 30%). C12H12N2O (200.09) calc. C(71.98),
H(6.04), N(13.99) found. C(71.43), H(6.21), N(13.21).
Methyl
5-methyl-4-oxo-1,2,3,4,5,6-hexahydroazepino[4,5-b]-
indole-5-carboxylate (28a). White solid M.p. 280 ◦C (dec.),
yield 35%. IR (KBr cm-1) 3349, 2963, 2899, 1731, 1650, 1457;
1H-NMR (300 MHz, DMSO-d6) d/ppm: 1.80 (s, 3H), 2.71–2.90
(m, 2H), 3.18–3.36 (m, 2H, plus large overlapping H2O peak),
3.65 (s, 3H), 6.98 (dt, J = 7.8 Hz, J = 1.2 Hz, 1H), 7.09 (dt, J =
7.2 Hz, J = 1.2 Hz, 1H), 7.33–7.40 (m, 2H), 8.04 (brt, J = 6.3 Hz,
1H, NHC O), 10.73 (brs, 1H); 13C-NMR (75 MHz, DMSO-d6)
=
5-Methyl-2,3,5,6-tetrahydroazepino[4,5-b]indol-4(1H)-one (23).
d/ppm: 173.1, 170.3, 135.2, 128.9, 127.8, 121.6, 118.6, 117.9,
111.1, 110.1, 53.2, 52.9, 38.3, 25.8, 21.4; MS (EI) m/z 272 (M+,
100%). C15H16N2O3 (272.12) calc. C(66.16), H(5.92), N(10.29)
found. C(65.57), H(5.93), N(10.59).
◦
White solid M.p. 219 C, yield 80%. IR (KBr cm-1) 3293, 3078,
2971, 2938, 2886, 1732, 1655, 1456; 1H-NMR (300 MHz, DMSO-
d6) d/ppm: 1.48 (d, J = 6.9 Hz, 3H), 2.71–2.86 (m, 2H), 3.34–3.40
(m, plus large overlapping H2O peak), 3.68–3.79 (m, 1H), 4.23–
4.29 (m, 1H), 6.95 (t, J = 7.5 Hz, 1H), 7.04 (t, J = 7.5 Hz, 1H), 7.33
Ethyl
5-methyl-4-oxo-1,2,3,4,5,6-hexahydroazepino[4,5-b]-
◦
=
(dd, J = 8.1 Hz, J = 3 Hz, 2H), 7.75 (brt, J = 6.6 Hz, 1H, NHC O),
indole-5-carboxylate (28b). White solid M.p 232 C, yield 10%
10.59 (s, 1H, NH); 13C-NMR (75 MHz, DMSO-d6) d/ppm: 174.4,
(55% yield when EtOH was used as the solvent). IR (KBr cm-1)
1
134.8, 131.2, 128.4, 120.6, 118.5, 117.3, 110.9, 107.8, 38.6, 36.2,
3418, 3220, 3100, 2958, 2922, 2853, 1709, 1673, 1456; H-NMR
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The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 1388–1396 | 1393
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