V. Andrianov et al. / European Journal of Medicinal Chemistry 44 (2009) 1067e1085
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1
1.01e1.78 (m, 6H), 2.25 (t, J ¼ 7.2 Hz, 2H), 3.16 (q,
J ¼ 6.0 Hz, 2H), 3.57 (s, 3H), 6.75 (d, J ¼ 16.0 Hz, 1H),
7.46 (d, J ¼ 16.0 Hz, 1H), 7.46 (dd, J ¼ 4.8, 8.0 Hz, 1H),
7.98 (dt, J ¼ 1.8, 8.0 Hz, 1H), 8.14 (t, J ¼ 5.3 Hz, 1H), 8.56
(dd, J ¼ 1.8, 4.8 Hz, 1H), 8.76 (d, J ¼ 1.8 Hz, 1H).
61%. H NMR (DMSO-d6, HMDSO) d: 1.12e1.67 (m, 6H),
2.31 (t, J ¼ 7.3 Hz, 2H), 3.19 (q, J ¼ 6.4 Hz, 2H), 3.58 (s,
3H), 6.83 (d, J ¼ 15.8 Hz, 1H), 7.54 (dd, J ¼ 4.2, 8.3 Hz,
1H), 7.62 (d, J ¼ 15.8 Hz, 1H), 7.81 (dd, J ¼ 1.4, 8.6 Hz,
1H), 8.00 (d, J ¼ 8.6 Hz, 1H), 8.15 (s, 1H), 8.19 (t,
J ¼ 5.8 Hz, 1H), 8.36 (dd, J ¼ 1.5, 8.3 Hz, 1H), 8.92 (dd,
J ¼ 1.5, 4.2 Hz, 1H).
4.1.21.2.
(E )-N-[6-(Hydroxyamino)-6-oxohexyl]-3-(3-pyri-
dinyl)-2-propenamide oxalate (25). A solution of sodium
methylate (6 mmol) in methanol (5 ml) was added to a solution
of hydroxylamine hydrochloride (0.28 g, 4 mmol) in methanol
(8 ml). The mixture was stirred for 10 min and NaCl was fil-
tered off. Methyl 6-{[(E )-3-(3-pyridinyl)-2-propenoyl]ami-
no}hexanoate (13j) (0.28 g, 1 mmol) was added to the
filtrate and the resultant mixture was stirred for 4 h at ambient
temperature. The solvent was removed under reduced pres-
sure, the product was dissolved in ethanol (10 ml) and then ox-
alic acid (0.36 g, 4 mmol) was added to the solution. The
precipitate was filtered and crystallized from water. (E )-N-
[6-(hydroxyamino)-6-oxohexyl]-3-(3-pyridinyl)-2-propena-
mide oxalate (25) (0.22 g, 68%) was obtained as a white solid.
4.1.23.2. (E )-N-[6-(Hydroxyamino)-6-oxohexyl]-3-(7-quino-
linyl)-2-propenamide (27). Compound 27 from methyl 6-
{[(E )-3-(7-quinolinyl)-2-propenoyl]amino}hexanoate
by a similar protocol to 16 was prepared, yield 58%. M.p.
(13l)
1
163e165 ꢁC. H NMR (DMSO-d6, HMDSO) d: 1.19e1.38
(m, 2H), 1.38e1.61 (m, 4H), 1.95 (t, J ¼ 7.2 Hz, 2H), 3.18
(q, J ¼ 6.6 Hz, 2H), 6.83 (d, J ¼ 15.8 Hz, 1H), 7.54 (dd,
J ¼ 4.3, 8.3 Hz, 1H), 7.62 (d, J ¼ 15.8 Hz, 1H), 7.81 (dd,
J ¼ 1.4, 8.5 Hz, 1H), 8.01 (d, J ¼ 8.5 Hz, 1H), 8.14 (s, 1H),
8.18 (t, J ¼ 5.8 Hz, 1H), 8.36 (dd, J ¼ 1.6, 8.3 Hz, 1H), 8.68
(br s, 1H), 8.92 (dd, J ¼ 1.6, 4.3 Hz, 1H), 10.35 (br s, 1H).
Anal. Calcd for C18H21N3O3$H2O: C 62.59, H 6.71, N
12.17. Found: C 62.44, H 6.69, N 11.83.
1
M.p. 157e159 ꢁC. H NMR (DMSO-d6, HMDSO) d: 1.03e
1.72 (m, 6H), 1.96 (t, J ¼ 7.2 Hz, 2H), 3.18 (q, J ¼ 6.0 Hz,
2H), 6.74 (d, J ¼ 15.8 Hz, 1H), 7.44 (d, J ¼ 15.8 Hz, 1H),
7.44 (dd, J ¼ 5.0, 8.0 Hz, 1H), 7.99 (dt, J ¼ 1.8, 8.0 Hz, 1H),
8.18 (t, J ¼ 5.2 Hz, 1H), 8.56 (dd, J ¼ 1.6, 5.0 Hz, 1H), 8.74
(d, J ¼ 2.0 Hz, 1H), 10.34 (br s, 1H). Anal. Calcd for
C14H19N3O3/0.5(COOH)2/2H2O: C 50.27, H 6.75, N
11.73. Found: C 50.28, H 6.71, N 11.60.
4.1.24. Preparation of 28
4.1.24.1. Methyl 6-{[(E )-3-(8-quinolinyl)-2-propenoyl]amino}-
hexanoate (13m). Compound 13m from (E )-3-(8-quino-
linyl)-2-propenoic acid [31] (12m) and methyl 6-
aminohexanoate hydrochloride by a similar protocol to 13a
1
was obtained, yield 46%. H NMR (DMSO-d6, HMDSO) d:
4.1.22. Preparation of 26
1.10e1.68 (m, 6H), 2.24 (t, J ¼ 7.1 Hz, 2H), 2.97 (q,
J ¼ 6.0 Hz, 2H), 3.61 (s, 3H), 6.97 (d, J ¼ 15.8 Hz, 1H),
7.53e7.78 (m, 2H), 7.95e8.13 (m, 2H), 8.26 (t, J ¼ 5.2 Hz,
1H), 8.44 (dd, J ¼ 1.6, 8.0 Hz, 1H), 8.60 (d, J ¼ 15.8 Hz,
1H), 9.00e9.17 (m, 1H).
4.1.22.1. Methyl 6-{[(E )-3-(2-naphthyl)-2-propenoyl]amino}-
hexanoate (13k). Compound 13k from (E )-3-(2-naphthyl)-2-
propenoic acid (12k) and methyl 6-aminohexanoate hydro-
chloride by a similar protocol to 13a was obtained, yield
94%. M.p. 74e76 ꢁC. 1H NMR (DMSO-d6, HMDSO) d:
1.10e1.78 (m, 6H), 2.25 (t, J ¼ 6.5 Hz, 2H), 3.21 (q,
J ¼ 5.6 Hz, 2H), 3.58 (s, 3H), 6.78 (d, J ¼ 15.5 Hz, 1H),
7.46e8.23 (m, 9H).
4.1.24.2. (E )-N-[6-(Hydroxyamino)-6-oxohexyl]-3-(8-quino-
linyl)-2-propenamide (28). Compound 28 from methyl 6-
{[(E )-3-(8-quinolinyl)-2-propenoyl]amino}hexanoate (12m)
by a similar protocol to 16 was prepared, yield 52%. M.p.
1
120e122 ꢁC. H NMR (DMSO-d6, HMDSO) d: 1.19e1.39
4.1.22.2.
(E )-N-[6-(Hydroxyamino)-6-oxohexyl]-3-(2-naph-
(m, 2H), 1.39e1.66 (m, 4H), 1.97 (t, J ¼ 7.2 Hz, 2H), 3.20
(q, J ¼ 6.6 Hz, 2H), 6.93 (d, J ¼ 16.0 Hz, 1H), 7.62 (dd,
J ¼ 4.2, 8.3 Hz, 1H), 7.67 (t, J ¼ 8.0 Hz, 1H), 8.02 (d,
J w 8.0 Hz, 1H), 8.05 (d, J w 8.0 Hz, 1H), 8.21 (t,
J ¼ 5.6 Hz, 1H), 8.42 (dd, J ¼ 1.6, 8.3 Hz, 1H), 8.63 (d,
J ¼ 16.0 Hz, 1H), 8.70 (br s, 1H), 9.00 (dd, J ¼ 1.6,
4.2 Hz, 1H), 10.37 (br s, 1H). Anal. Calcd for
C18H21N3O3/H2O: C 62.59, H 6.71, N 12.17. Found: C
62.36, H 6.52, N 11.97.
thyl)-2-propenamide (26). Compound 26 from methyl 6-
{[(E )-3-(2-naphthyl)-2-propenoyl]amino}hexanoate (13k) by
a similar protocol to 16 was prepared, yield 74%. M.p.
161e163 ꢁC. H NMR (DMSO-d6, HMDSO) d: 1.07e1.74
(6H, m, CH2), 1.81e2.14 (unresolved t, 2H), 3.03e3.41 (m,
2H), 6.74 (d, J ¼ 16.0 Hz, 1H), 7.43e8.21 (m, 9H), 8.63 (br
s, 1H), 10.32 (br s, 1H). Anal. Calcd for C19H22N2O5/
H2O: C 66.26, H 7.02, N 8.13. Found: C 66.51, H 7.11, N
8.01.
1
4.1.25. Preparation of 29
4.1.23. Preparation of 27
4.1.25.1. Methyl 6-[(6-quinolinylcarbonyl)amino]hexanoate
(13n). Compound 13n from quinoline-6-carboxylic acid
(12n) and methyl 6-aminohexanoate hydrochloride by a similar
protocol to 13a was obtained, yield 48%. 1H NMR (DMSO-d6,
HMDSO) d: 1.15e1.70 (m, 6H), 2.21 (t, J ¼ 7.1 Hz, 2H), 2.88
4.1.23.1. Methyl 6-{[(E )-3-(7-quinolinyl)-2-propenoyl]amino}-
hexanoate (13l). Compound 13l from (E )-3-(7-quinolinyl)-2-
propenoic acid [30] (12l) and methyl 6-aminohexanoate
hydrochloride by a similar protocol to 13a was obtained, yield