D. Carbonnelle et al. / European Journal of Medicinal Chemistry 42 (2007) 686e693
691
(t, 2H, CH2), 3.76 (s, 3H, NeCH3), 7.16 (dd, 1H, H6, J ¼ 8.8,
5.1.9. N-(4,6-Dimethylpyridin-2-yl)-3-[1-(4-chlorobenzyl)-
indol-3-yl]propanamide (22)
1.8 Hz), 7.22 (s, 1H, H2), 7.44 (d, 1H, H7), 7.61 (d, 1H, H4).
Oil, yield: 58%; IR (NaCl, cmꢃ1): n(NH) 3270, n(C]O)
1680; 1H NMR (DMSO-d6, ppm): d 2.28 (s, 3H, g-CH3),
2.37 (s, 3H, a-CH3), 2.77 (t, 2H, CH2eCO, J ¼ 7.3 Hz),
3.04 (t, 2H, CH2), 5.38 (s, 2H, NeCH2), 6.82 (s, 1H, pyr.
H5), 7.09 (m, 4H, H5, H6, Bn. H2, H6), 7.23 (d, 2H, Bn. H3,
H5, J ¼ 8.4 Hz), 7.32 (s, 1H, H2), 7.41 (d, 1H, H7,
J ¼ 7.9 Hz), 7.63 (d, 1H, H4, J ¼ 7.3 Hz), 7.82 (s, 1H, pyr.
H3), 10.39 (s, 1H, NH). Anal. C25H24ClN3O (C, H, N).
5.1.5. Method h: N-(Pyridin-4-yl)-3-(5-chloro-1-
methylindol-3-yl)propanamide (19)
To a solution of 3-(5-chloro-1-methylindol-3-yl)propanoic
acid 14 (0.40 g, 1.68 mmol) in dry CH2Cl2 (50 mL), were added
2-chloro-1-methylpyridinium iodide (0.429 g, 1.68 mmol), trie-
thylamine (0.60 mL, 4.20 mmol)and 4-aminopyridine (0.174 g,
1.85 mmol). The mixture was refluxed for 12 h and after cool-
ing, washed with water, dried over Na2SO4 and concentrated.
The crude was purified by chromatography on silica gel using
dichloromethaneeethanol 95:5 as the eluent. Trituration in dii-
sopropylic ether afforded 19 as awhite powder. Yield: 61%; m.p.
(dec.): 165e166 ꢂC; IR (KBr, cmꢃ1): n(NH) 3246, n(C]O)
5.1.10. N-(4,6-Dimethylpyridin-2-yl)-3-[5-chloro-1-
(4-chlorobenzyl)indol-3-yl]propanamide (23)
White powder, yield: 27%; m.p. (dec.): 90e91 ꢂC; IR (KBr,
cmꢃ1): n(NH) 3207, n(C]O) 1663; 1H NMR (DMSO-d6,
ppm): d 2.28 (s, 3H, g-CH3), 2.37 (s, 3H, a-CH3), 2.74 (t,
2H, CH2eCO, J ¼ 7.3 Hz), 3.02 (t, 2H, CH2), 5.39 (s, 2H,
CH2), 6.82 (s, 1H, pyr. H5), 7.12 (d, 2H, Bn. H2, H6,
J ¼ 8.5 Hz), 7.15 (dd, 1H, H6, J ¼ 8.5, 1.8 Hz), 7.23 (d, 2H,
Bn. H3, H5), 7.41 (s, 1H, H2), 7.45 (d, 1H, H7), 7.71 (d, 1H,
H4), 7.81 (s, 1H, pyr. H3), 10.39 (s, 1H, NH). Anal.
C25H23Cl2N3O (C, H, N).
1
1719; H NMR (DMSO-d6, ppm): d 2.73 (t, 2H, CH2eCO,
J ¼ 7.9 Hz), 3.03 (t, 2H, CH2), 3.76 (s, 3H, NeCH3), 7.16 (dd,
1H, H6, J ¼ 8.8, 2.4 Hz), 7.23 (s, 1H, H2), 7.44 (d, 1H, H7),
7.59 (d, 2H, pyr. H3, H5, J ¼ 5.9 Hz), 7.66 (d, 1H, H4), 8.44
(d, 2H, pyr. H2, H6), 10.32 (s, 1H, NH). Anal. C17H16ClN3O
(C, H, N).
5.1.6. N-(Pyridin-4-yl)-3-(1-benzylindol-3-yl)-
propanamide (17)
5.1.11. N-[(Pyridin-3-yl)methyl]-3-(1-benzylindol-3-yl)-
propanamide (25)
Yield: 69%; m.p. (dec.): 140e141 ꢂC; IR (KBr, cmꢃ1):
n(NH) 3290, n(C]O) 1690; 1H NMR (DMSO-d6, ppm):
d 2.76 (t, 2H, CH2eCO, J ¼ 7.0 Hz), 3.08 (t, 2H, CH2), 5.38
(s, 2H, NeCH2), 7.15 (m, 7H, H5, H6, Bn), 7.31 (s, 1H, H2),
7.43 (d, 1H, H7, J ¼ 7.9 Hz), 7.60 (m, 3H, H4, pyr. H3, H5),
8.44 (d, 2H, pyr. H2, H6, J ¼ 4.9 Hz), 10.33 (s, 1H, NH).
Anal. C23H21N3O (C, H, N).
White powder, yield: 78%; m.p. (dec.): 124e125 ꢂC; IR
(KBr, cmꢃ1): n(NH) 3311, n(C]O) 1642; 1H NMR
(DMSO-d6, ppm): d 2.53 (t, 2H, CH2eCO, J ¼ 7.5 Hz), 3.01
(t, 2H, CH2), 4.31 (d, 2H, NHeCH2, J ¼ 5.8 Hz), 5.37 (s,
2H, NeCH2), 7.02 (dd, 1H, H5, J ¼ 7.9, 7.0 Hz), 7.12 (dd,
1H, H6, J ¼ 7.9, 7.0 Hz), 7.27 (m, 7H, H2, pyr. H5, Bn), 7.42
(d, 1H, H7), 7.55 (m, 2H, H4, pyr. H4), 8.43 (m, 3H, NH,
pyr. H2, pyr. H6). Anal. C24H23N3O (C, H, N).
5.1.7. N-(Pyridin-4-yl)-3-[1-(4-chlorobenzyl)indol-3-yl]-
propanamide (18)
5.1.12. N-[(Pyridin-3-yl)methyl]-3-[1-(4-chlorobenzyl)-
indol-3-yl]propanamide (26)
White powder; Yield: 64%; m.p. (dec): 137e138 ꢂC; IR
(KBr, cmꢃ1): n(NH) 3280, n(C]O) 1695; 1H NMR
(DMSO-d6, ppm): d 2.76 (t, 2H, CH2eCO, J ¼ 7.7 Hz), 3.07
(t, 2H, CH2), 5.38 (s, 2H, NeCH2), 7.05 (dd, 1H, H6,
J ¼ 7.9, 7.6 Hz), 7.13 (dd, 1H, H5, J ¼ 7.6, 7.1 Hz), 7.17 (d,
2H, Bn. H2, H6, J ¼ 8.4 Hz), 7.31 (d, 2H, Bn. H3, H5), 7.32
(s, 1H, H2), 7.42 (d, 1H, H7), 7.60 (d, 2H, pyr. H3, H5,
J ¼ 5.0 Hz), 7.63 (d, 1H, H4), 8.44 (d, 2H, pyr. H2, H6),
10.33 (s, 1H, NH). Anal. C23H20ClN3O (C, H, N).
Yield: 78%; m.p. (dec.): 121e122 ꢂC; IR (KBr, cmꢃ1):
n(NH) 3334, n(C]O) 1643; 1H NMR (DMSO-d6, ppm):
d 2.56 (t, 2H, CH2eCO, J ¼ 7.5 Hz), 3.00 (t, 2H, CH2), 4.31
(d, 2H, NHCH2, J ¼ 5.9 Hz), 5.37 (s, 2H, NCH2), 7.04 (dd,
1H, H5, J ¼ 8.0, 7.6 Hz), 7.13 (dd, 1H, H6, J ¼ 8.0, 7.2 Hz),
7.20 (d, 2H, Bn. H2, H6, J ¼ 8.8 Hz), 7.30 (dd, 1H, pyr. H5,
J ¼ 8.0, 4.8 Hz), 7.38 (d, 2H, Bn. H3, H5), 7.41 (d, 1H, H7),
7.55 (d, 1H, pyr. H4), 7.59 (d, 1H, H4), 8.46 (m, 3H, NH,
pyr. H2, H6). Anal. C24H22ClN3O (C, H, N).
5.1.8. N-(4,6-Dimethylpyridin-2-yl)-3-(1-benzylindol-3-yl)-
propanamide (21)
5.1.13. N-[(Pyridin-3-yl)methyl]-3-(5-chloro-1-methylindol-
3-yl)propanamide (27)
White powder, yield: 52%; m.p. (dec.): 110e111 ꢂC; IR
(KBr, cmꢃ1): n(NH) 3273, n(C]O) 1669. 1H NMR
(DMSO-d6, ppm): d 2.29 (s, 3H, g-CH3), 2.37 (s, 3H, a-
CH3), 2.77 (t, 2H, CH2eCO, J ¼ 7.0 Hz), 3.04 (t, 2H, CH2),
5.37 (s, 2H, NeCH2), 6.82 (s, 1H, pyr. H5), 7.12 (m, 7H,
H5, H6, Bn), 7.32 (s, 1H, H2), 7.42 (d, 1H, H7, J ¼ 7.6 Hz),
7.63 (d, 1H, H4, J ¼ 7.0 Hz), 7.82 (s, 1H, pyr. H3), 10.40 (s,
1H, NH). Anal. C25H25N3O (C, H, N).
White powder, Yield: 82%; m.p. (dec.): 106e107 ꢂC; IR
(KBr, cmꢃ1): n(NH) 3334, n(C]O) 1643; 1H NMR
(DMSO-d6, ppm): d 2.51 (t, 2H, CH2eCO, J ¼ 7.2 Hz), 2.96
(t, 2H, CH2), 3.75 (s, 3H, NCH3), 4.31 (d, 2H, NHeCH2,
J ¼ 6.0 Hz), 7.14 (dd, 1H, H6, J ¼ 8.4, 2.0 Hz), 7.16 (s, 1H,
H2), 7.32 (dd, 1H, pyr. H5, J ¼ 7.6, 4.8 Hz), 7.44 (d, 1H,
H7), 7.52 (d, 1H, pyr. H4), 7.63 (d, 1H, H4), 8.45 (m, 3H,
NH, pyr. H2, H6). Anal. C18H18ClN3O (C, H, N).