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H), 3.57 (s, 2H), 6.88 (d, 1 H, J ) 16.3 Hz), 7.01 – 7.11 (m,
1H), 7.18–7.22 (m, 1 H), 7.29 (d, 1 H, J ) 8.5 Hz), 7.46 (d, 1
H, J ) 8.1 Hz), 7.65–7.71 (m, 3 H), 8.11 (d, 1 H, J ) 1.8 Hz),
10.30 (s, 1 H), 11.63 (s, 1 H); 13C NMR 21.2 (prim C), 31.7
(sec C), 111.4, 118.1, 119.2, 122.4, 122.6, 126.9, 128.1, 129.7,
142.5 (tert C), 107.6, 122.9, 126.5, 126.8, 131.9, 137.0, 137.5,
171.3, 198.0 (quat C); (C20H16N2O2) HRMS (EI) (m/z) calcd for
[M+], 316.12119; found, 316.12039.
General Procedure C for the Preparation of 2-[(1E)-3-Aryl-
3-oxo-1-propenyl]-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-
ones 12 by Heck-Type Reaction with Ketone Mannich Bases.
A mixture of a 9-substituted 2-iodo-7,12-dihydroindolo[3,2-
d][1]benzazepin-6(5H)-one (0.50 mmol; 7a, b, or e), a ketone
Mannich base hydrochloride (0.55 mmol), palladium(II)acetate
(11 mg, 0.050 mmol), triphenylphosphine (13 mg, 0.050 mmol),
triethylamine (2 mL), and DMF (10 mL) is stirred at 150 °C
under nitrogen. After filtration, silica gel (1.5 g) is added to the
filtrate and the solvent is evaporated. The remaining silica gel/
reaction product mixture is added onto a silica gel pad in a glass
frit and is then eluted with ethyl acetate (200 mL). After
evaporation of the solvent the remaining solid is purified by
crystallization from ethanol. For the synthesis of the derivatives
12a-c and 12g-m, the procedure was adapted to the use of a
parallel synthesis reactor. In this case, the reaction was carried
out without addition of triphenylphosphine in 20 mL vials with
2 mL DMF as solvent. The vessel reactor block temperature
was set to 140 °C. The work-up procedure was carried out as
described above.
2-[(1E)-3-Oxo-3-phenyl-1-propenyl]-7,12-dihydroindolo[3,2-
d][1]benzazepin-6(5H)-one (12a). Preparation following general
procedure C from 2-iodo-7,12-dihydroindolo[3,2-d][1]benzazepin-
6(5H)-one (7a)8 and N,N-dimethyl-3-oxo-3-phenyl-1-propan-
aminium chloride37 yielded 40% of a yellow solid, mp 256 °C
1
(dec); IR 3309 (NH), 3222 (NH), 1652 (CdO); H NMR 3.59
(s, 2 H), 7.10 (ddd, 1 H, J ) 9.0/7.97 Hz), 7.21 (ddd, 1 H, J )
8.0/1.1 Hz), 7.33 (d, 2 H, J ) 8.5 Hz), 7.49 (d, 2 H, J ) 8.1
Hz), 7.59 – 7.63 (m, 2 H), 7.68 – 7.72 (m, 2 H), 7.81 (d, 2 H,
J ) 15.6 Hz), 7.91 (dd, 1 H, J ) 8.6/2.0 Hz), 7.98 (d, 1 H),
8.16 – 8.18 (m, 2 H), 8.25 (d, 1H, J ) 1.9 Hz,), 10.34 (s, 1 H),
11.63 (s, 1 H); 13C NMR 31.6 (sec C), 111.4, 118.0, 119.1, 121.4,
122.3, 122.4, 127.6, 128.3, 128.4 (2 C), 128.8 (2 C), 133.0, 143.3
(tert C), 107.5, 122.8, 126.4, 129.8, 131.8, 137.1, 137.4, 137.5,
171.2, 189.0 (quat C); (C25H18N2O2) HRMS (EI; m/z, M+) calcd,
378.13681; found, 378.13611.
(16) Kunick, C.; Schultz, C.; Lemcke, T.; Zaharevitz, D. W.; Gussio, R.;
Jalluri, R. K.; Sausville, E. A.; Leost, M.; Meijer, L. 2-Substituted
paullones: CDK1/cyclin B-inhibiting property and in vitro antiprolif-
erative activity. Bioorg. Med. Chem. Lett. 2000, 10, 567–569.
¨
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Ber. Dtsch. Chem. Ges. 1922, 55, 3510–3526.
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carbonyl group. Zh. Obshch. Khim. 1958, 28, 680–682.
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Acknowledgment. Funding of the project by the European
Commission (Contract No LSHB-CT-2004-503467) is gratefully
acknowledged.
(20) Barabanov, I. I.; Fedenok, L.; Polyakov, N. E.; Shvartzberg, M. S.
Transformations of 1-amino-2-(3-hydroxyalkyl-1-ynyl)-9,10-anthaquino-
nes in the presence of amines. Russ. Chem. Bull., Int. Ed. 2001, 9,
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Supporting Information Available: Details for the synthesis
of compounds 7c–e, 10b-f, 12b-m, 14, and 15, spectroscopic data,
HPLC purity data, and data of elemental analyses. This material is
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