J.L. Falcó et al. / European Journal of Medicinal Chemistry 41 (2006) 985–990
989
5.1.2. General procedure for preparation of 1H-indole
derivatives (6)
(DMSO, ppm) δ 7.43–6.49 (m, Ar, 9H), 4.99 (s, CH2, 2H),
3.56–3.40 (m, morpholine, 8H), 2.41 (s, Me, 3H). H NMR
1
10m: (DMSO, ppm) δ 7.81–6.81 (m, Ar, 9H), 5.00 (s, CH2,
To 1 eq of the hydrazine (4) is added 1 eq of the phenone
(5), and the resulting mixture is stirred at 100 °C for 30 min.
The water is removed in vacuo, and a solution of 5 eq of ZnCl2
in DMA is added. The mixture is stirred at 170 °C for 12 h.
After this period, the crude is allowed to cool and is extracted
with DCM/water. The organic layer is dried over MgSO4, fil-
tered off and the solvent is removed in vacuo, to obtain the
desired 1H-indole (6).
2H), 3.70 (m, thiomorpholine, 4H), 2.50 (m, thiomorpholine,
1
4H), 2.40 (s, Me, 3H). H NMR 10n: (DMSO, ppm) δ 7.76–
6.44 (m, Ar, 8H), 4.90 (s, CH2, 2H), 3.33 (m, CH2, 4H), 2.40
1
(s, Me, 3H), 2.34 (s, Me, 3H), 1.04 (m, Me, 6H). H NMR
10p: (DMSO, ppm) δ 7.43–6.43 (m, Ar, 8H), 4.92 (s, CH2,
2H), 3.24 (m, CH2, 4H), 2.39 (s, Me, 3H), 2.34 (s, Me, 3H),
1
1.47 (m, CH2, 4H), 0.81 (m, Me, 6H). H NMR 10q: (DMSO,
ppm) δ 7.43–6.42 (m, Ar, 8H), 4.90 (s, CH2, 2H), 3.25
(m, CH2, 4H), 2.39 (s, Me, 3H), 2.34 (s, Me, 3H), 1.42 (m,
CH2, 4H), 1.22 (m, CH2, 4H), 0.85 (m, Me, 6H). H NMR
5.1.3. General procedure for preparation of 1H-benzimidazole
derivatives (13)
1
10r: (DMSO, ppm) δ 7.43–6.44 (m, Ar, 8H), 4.97 (s, CH2,
2H), 3.57 (m, morpholine, 8H), 2.40 (s, Me, 3H), 2.35 (s,
Me, 3H).
To a solution of 1 eq of the aldehyde (12) in DMF are
added 1 eq of the amine (11) and 4 eq of Na2S2O5, and the
resulting mixture is stirred at 120 °C for 12 h. After this period,
the crude is allowed to cool and is solved in ethyl acetate. To
the resulting solution is added water, and the solid thus ob-
tained is filtered off and washed with water, to obtain the de-
sired 1H-benzimidazole (13).
5.1.5. General procedure for preparation of N,N-disubstituted-
benzoimidazol-1-yl-acetamide derivatives (14)
To a suspension of 2.2 eq of potassium carbonate in aceto-
nitrile are added 1.2 eq of chloroacetamide (9) and 1 eq of
benzimidazole (13). The mixture is stirred at reflux for 12 h.
The crude is allowed to cool and it is filtered off. The solvent is
removed in vacuo, to obtain the desired product (14).
5.1.4. General procedure for preparation of N,N-disubstituted-
indol-1-yl-acetamide derivatives (10)
1.2 eq of NaH are added to DMF under argon. To this mix-
ture, 1 eq of the indole (6) is added and the mixture is stirred
under argon at room temperature for 2 h. The crude is cooled
to 0 °C and 3 eq of chloroacetamide (9) are added very slowly.
The mixture is stirred at room temperature for 12 h. After this
period, methanol is added to the crude and the solvent is re-
moved in vacuo. The residue is extracted with DCM/water.
The organic layer is dried over MgSO4, filtered off and the
solvent is removed in vacuo, to obtain the desired product (10).
1H NMR 10a: (CDCl3, ppm) δ 7.63–6.59 (m, Ar, 10H),
1H NMR 14a: (DMSO, ppm) δ 7.90–7.27 (m, Ar, 7H), 5.29
1
(s, CH2, 2H), 3.24 (m, CH2, 4H), 0.92 (m, Me, 6H). H NMR
14b: (DMSO, ppm) δ 7.96–7.27 (m, Ar, 7H), 5.35 (s, CH2,
1
2H), 3.62–3.44 (m, morpholine, 8H). H NMR 14c: (DMSO,
ppm) δ 7.51–7.02 (m, Ar, 7H), 5.09 (s, CH2, 2H), 3.32 (m,
CH2, 4H), 2.41 (s, Me, 3H), 2.36 (s, Me, 3H), 1.02 (m, Me,
1
6H). H NMR 14d: (CDCl3, ppm) δ 7.69–7.01 (m, Ar, 7H),
4.89 (s, CH2, 2H), 3.03 (m, Me, 6H), 2.49 (s, Me, 3H), 2.42
(s, Me, 3H). 1H NMR 14e: (DMSO, ppm) δ 7.72–6.84 (m, Ar,
7H), 5.18 (s, CH2, 2H), 3.79 (s, MeO, 3H), 3.20 (m, CH2, 4H),
1
4.85 (s, CH2, 2H), 2.99 (s, Me, 3H), 2.93 (s, Me, 3H). H
1
NMR 10b: (DMSO, ppm) δ 7.91–6.47 (m, Ar, 8H), 4.95 (s,
1.56 (m, CH2, 4H), 1.40 (m, CH2, 4H), 0.80 (m, Me, 6H). H
CH2, 2H), 3.29 (m CH2, 4H), 2.47 (s, Me, 3H), 1.04 (m, Me,
NMR 14f: (DMSO, ppm) δ 7.73–6.83 (m, Ar, 7H), 5.08 (s,
CH2, 2H), 3.79 (s, MeO, 3H), 3.53 (m, pyrrol, 4H), 1.84 (m,
pyrrol, 4H).
1
6H). H NMR 10c: (DMSO, ppm) δ 7.49–6.54 (m, Ar, 8H),
4.95 (s, CH2, 2H), 3.22 (m, CH2, 4H), 2.38 (s, Me, 3H), 1.44
(m, CH2, 4H), 0.77 (m, Me, 6H). 1H NMR 10d: (DMSO, ppm)
δ 7.50–6.46 (m, Ar, 8H), 4.95 (s, CH2, 2H), 3.22 (m, CH2,
4H), 2.07 (s, Me, 3H), 1.40 (m, CH2, 4H), 1.21 (m, CH2,
References
1
4H), 0.85 (m, Me, 6H). H NMR 10e: (DMSO, ppm) δ 7.55–
[1] E.N. Peterson, Benzodiazepine receptor pharmacology: new vistas,
6.47 (m, Ar, 8H), 4.88 (s, CH2, 2H), 3.47 (m, CH2, 2H), 3.29
(m, CH2, 2H), 2.07 (s, Me, 3H), 1.89 (m, CH2, 2H), 1.57 (m,
CH2, 2H). H NMR 10f: (CDCl3, ppm) δ 7.52–6.63 (m, Ar,
Drugs Future 12 (1987) 1043–1053.
1
[2] E.A. Barnard, P. Skolnick, R.W. Olsen, H. Mohler, W. Sieghart, G. Big-
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Pharmacology. XV. Subtypes of γ-aminobutyric acidA receptors: classi-
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8H), 4.86 (s, CH2, 2H), 3.70–3.42 (m, morpholine, 8H), 2.61
1
(s, Me, 3H). H NMR 10g: (CDCl3, ppm) δ 7.52–6.65 (m, Ar,
8H), 5.01 (s, CH2, 2H), 3.80–3.50 (m, thiomorpholine, 8H),
1
2.53 (s, Me, 3H). H NMR 10 h: (DMSO, ppm) δ 7.83–6.48
[3] F. McGillion, Aspects of the current status of benzodiazepine therapy,
Drugs Today 25 (1987) 27–31.
(m, Ar, 9H), 4.92 (s, CH2, 2H), 3.29 (m, CH2, 4H), 2.39
1
[4] H.C. Rosenberg, E.I. Tietz, T.H. Chiu, Tolerance to anticonvulsant ef-
fects of diazepam, clonazepam, and clobazam in amygdala-kindled rats,
Epylepsia 30 (1989) 276–285.
(s, Me, 3H), 1.02 (m, Me, 6H). H NMR 10i: (DMSO, ppm)
δ 7.44–6.48 (m, Ar, 9H), 4.94 (s, CH2, 2H), 3.24 (m, CH2,
4H), 2.39 (s, Me, 3H), 1.47 (m, CH2, 4H), 0.80 (m, Me, 6H).
1H NMR 10j: (DMSO, ppm) δ 7.45–6.47 (m, Ar, 9H), 4.96
(s, CH2, 2H), 3.25 (m, CH2, 4H), 2.40 (s, Me, 3H), 1.40 (m,
CH2, 4H), 1.20 (m, 4H, CH2), 0.84 (m, Me, 6H). 1H NMR 10l:
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A. Imidazopyridines: towards novel hypnotic and anxiolytic drugs. Il
Farmaco 1991, 46, 277–288. (b) Browne, L.J.; Shaw, K.J. New anxioly-
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