E. Lager et al. / Bioorg. Med. Chem. 16 (2008) 6936–6948
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5.58. Ethyl (2E)-3-[(4-benzylphenyl)amino]-2-(cyclopentylace-
tyl) acrylate (55)
The reaction yielded 59 (46%), a yellow oil. 1H NMR (CDCl3) d 0.94
(3H, t, J = 7.6), 1.34 (3H, t, J = 7.1), 1.38 (2H, m), 1.62 (2H, quint,
J = 7.5), 2.96 (2H, t, J = 7.5), 3.96 (2H, s), 4.25 (2H, q, J = 7.1), 7.15
(6H, m), 8.49 (3H, m), 12.80 (1H, d, J = 13.0); 13C NMR (CDCl3) d
14.0, 14.4, 25.6, 27.0, 40.5, 42.0, 59.9, 102.4, 117.6, 118.0, 118.0,
124.1, 124.1, 130.4, 130.4, 136.1, 137.9, 149.7, 149.7, 151.9,
166.8, 203.0. HRMS (ESI): for C22H27N2O3 calcd: 367.2022 [MH]+;
found: 367.2015.
The title compound was prepared and purified according to the
procedure described for 41, starting from 27g as reacting b-keto es-
ter and using 4-benzylaniline instead of 4-ethylaniline. The reac-
tion yielded 55 (72%), a yellow oil. 1H NMR (CDCl3) d 1.22 (2H,
m), 1.34 (3H, t, J = 7.1), 1.55 (2H, m), 1.63 (2H, m), 1.84 (2H, m),
2.33 (1H, m), 3.01 (2H, d, J = 7.1), 3.97 (2H, s), 4.26 (2H, q,
J = 7.1), 7.11 (2H, d, J = 8.4), 7.18 (3H, m), 7.22 (2H, d, J = 7.5),
7.30 (2H, t, J = 7.5), 8.48 (1H, d, J = 13.1), 12.83 (1H, d, J = 13.1);
13C NMR (CDCl3) d 14.4, 24.9, 24.9, 32.6, 32.6, 36.2, 41.1, 48.2,
59.7, 102.3, 117.7, 117.7, 126.2, 128.5, 128.5, 128.7, 128.7, 130.1,
130.1, 137.3, 138.5, 140.5, 151.9, 166.8, 202.5. HRMS (ESI): for
5.63. Ethyl (2E)-2-pentanoyl-3-{[4-(pyridin-3-ylmethyl)phenyl]-
amino} acrylate (60)
The title compound was prepared and purified according to the
procedure described for 41, but using 39 instead of 4-ethylaniline.
The reaction yielded 60 (48%), a yellow oil. 1H NMR (CDCl3) d 0.90
(3H, t, J = 7.3), 1.30 (3H, t, J = 7.1), 1.35 (2H, m), 1.59 (2H, quint,
J = 7.5), 2.93 (2H, t, J = 7.5), 3.93 (2H, s), 4.22 (2H, q, J = 7.1), 7.09
(2H, d, J = 8.5), 7.18 (3H, m), 7.43 (1H, m), 8.44 (3H, m), 12.77
(1H, d, J = 13.2); 13C NMR (CDCl3) d 13.9, 14.3, 22.5, 26.9, 38.2,
41.9, 59.8, 102.3, 117.8, 117.8, 123.4, 130.1, 130.1, 135.9, 136.1,
137.0, 137.6, 147.6, 149.9, 151.8, 166.7, 202.8. HRMS (ESI): for
C
25H30NO3 calcd: 392.2226 [MH]+; found: 392.2222.
5.59. Ethyl (2E)-2-pentanoyl-3-{[4-(2-phenylethyl)phenyl]-
amino}acrylate (56)
The title compound was prepared and purified according to the
procedure described for 41, but using 35 instead of 4-ethylaniline.
The reaction yielded 56 (46%), a yellow oil. 1H NMR (CDCl3) d 0.99
(3H, t, J = 7.3), 1.39 (3H, t, J = 7.1), 1.43 (2H, m), 1.67 (2H, quint,
J = 7.5), 2.96 (4H, s), 3.01 (2H, t, J = 7.5), 4.30 (2H, q, J = 7.1), 7.13
(2H, d, J = 8.5), 7.22 (5H, m), 7.32 (2H, d, J = 7.1), 8.53 (1H, d,
J = 13.2), 12.84 (1H, d, J = 13.2); 13C NMR (CDCl3) d 14.0, 14.4,
22.6, 27.0, 37.1, 37.7, 42.0, 59.8, 102.0, 117.6, 117.6, 125.9, 128.3,
128.3, 128.4, 128.4, 129.8, 129.8, 137.1, 139.1, 141.1, 152.0,
166.9, 202.8. HRMS (ESI): for C24H30NO3 calcd: 380.2226 [MH]+;
found: 380.2222.
C
22H27N2O3 calcd: 367.2022 [MH]+; found: 367.2017.
5.64. Ethyl (2E)-2-pentanoyl-3-{[4-(pyridin-2-ylmethyl)-
phenyl]amino} acrylate (61)
The title compound was prepared and purified according to the
procedure described for 41, but using 4022 instead of 4-ethylani-
line. The reaction yielded 61 (51%), a yellow oil. 1H NMR (CDCl3)
d 0.88 (3H, t, J = 7.3), 1.27 (3H, t, J = 7.1), 1.33 (2H, m), 1.57 (2H,
quint, J = 7.5), 2.90 (2H, t, J = 7.5), 4.07 (2H, s), 4.19 (2H, q,
J = 7.1), 7.05 (4H, m), 7.22 (2H, d, J = 8.3), 7.52 (1H, dt, J = 7.7,
1.5), 8.42 (1H, d, J = 13.1), 8.48 (1H, m), 12.74 (1H, d, J = 13.1);
13C NMR (CDCl3) d 13.8, 14.3, 22.4, 26.8, 41.8, 43.7, 59.6, 102.0,
117.7, 117.7, 121.2, 122.8, 130.2, 130.2, 136.4, 136.7, 137.3,
149.2, 151.8, 160.2, 166.6, 202.6. HRMS (ESI): for C22H27N2O3
calcd: 367.2022 [MH]+; found: 367.2015.
5.60. Ethyl (2E)-2-pentanoyl-3-{[4-(3-phenylpropyl)phenyl]-
amino} acrylate (57)
The title compound was prepared and purified according to the
procedure described for 41, but using 36 instead of 4-ethylaniline.
The reaction yielded 57 (60%), a yellow oil. 1H NMR (CDCl3) d 0.96
(3H, t, J = 7.3), 1.35 (3H, t, J = 7.1), 1.40 (2H, m), 1.64 (2H, m), 1.95
(2H, m), 2.65 (4H, m), 2.98 (2H, t, J = 7.5), 4.27 (2H, q, J = 7.1), 7.11
(2H, d, J = 8.5), 7.20 (5H, m), 7.30 (2H, m), 8.50 (1H, d, J = 13.2),
12.83 (1H, d, J = 13.2); 13C NMR (CDCl3) d 14.0, 14.5, 22.6, 27.1,
32.8, 34.7, 35.3, 42.0, 59.8, 102.0, 117.7, 117.7, 125.8, 128.3, 128.3,
128.3, 128.3, 129.7, 129.7, 137.0, 139.8, 141.9, 152.1, 166.9, 202.8.
HRMS (ESI): for C25H32NO3 calcd: 394.2382 [MH]+; found: 394.2384.
5.65. Ethyl (2E)-2-(cyclopentylacetyl)-3-{[4-(pyridin-3-ylmethyl)
phenyl]amino}acrylate (62)
The title compound was prepared and purified according to the
procedure described for 41, starting from 27g as reacting b-keto es-
ter and using 39 instead of 4-ethylaniline. The reaction yielded 62
(38%), a yellow oil. 1H NMR (CDCl3) d 1.14 (2H, m), 1.29 (3H, t,
J = 7.1), 1.53 (4H, m), 1.78 (2H, m), 2.26 (1H, m), 2.95 (2H, d,
J = 7.1), 3.92 (2H, s), 4.20 (2H, q, J = 7.1), 7.08 (2H. d. J = 8.5), 7.16
(3H, m), 7.41 (1H, d, J = 7.8), 8.43 (3H, m), 12.8 (1H, d, J = 13.2);
13C NMR (CDCl3) d 14.3, 24.8, 24.8, 32.5, 32.5, 36.1, 38.2, 48.1,
59.7, 102.4, 117.8, 117.8, 123.3, 130.0, 130.0, 135.9, 136.1, 136.9,
137.6, 147.6, 149.8, 151.7, 166.7, 202.5. HRMS (ESI): for
5.61. Ethyl (2E)-3-{[4-(2-naphthylmethyl)phenyl]amino}-2-
pentanoylacrylate (58)
The title compound was prepared and purified according to the
procedure described for 41, but using 37 instead of 4-ethylaniline.
The reaction yielded 58 (68%), a yellow oil. 1H NMR (CDCl3) d 0.99
(3H, t, J = 7.3), 1.36 (3H, t, J = 7.1), 1.43 (2H, m), 1.67 (2H, quint,
J = 7.5), 3.01 (2H, t, J = 7.5), 4.13 (2H, s), 4.28 (2H, q, J = 7.1),
7.12 (2H, d, J = 8.4), 7.25 (2H, d, J = 8.4), 7.31 (1H, dd, J = 8.4,
1.6), 7.47 (2H, m), 7.63 (1H, br s), 7.81 (3H, m), 8.51 (1H, d,
J = 13.2), 12.85 (1H, d, J = 13.2); 13C NMR (CDCl3) d 14.0, 14.4,
22.5, 27.0, 41.3, 42.0, 59.8, 102.1, 117.7, 117.7, 125.4, 126.0,
127.0, 127.3, 127.4, 127.5, 128.1, 130.2, 130.2, 132.0, 133.5,
137.3, 138.0, 138.4, 151.9, 166.8, 202.8. HRMS (ESI): for
C
24H29N2O3 calcd: 393.2178 [MH]+; found: 393.2166.
5.66. Ethyl (2E)-3-amino-2-pentanoylacrylate (63)
The acyl-ethoxy acrylate-intermediate was prepared as de-
scribed in the synthesis of 41. This crude intermediate was stirred
at rt in 5 ml of 2.0 M NH3 solution in EtOH for 5 h. Solvent was
evaporated under reduced pressure and the crude product was
purified by chromatography (petroleum ether/ethyl acetate, 6:1)
yielding 63 (42%), a yellow oil. 1H NMR (CDCl3) d 0.93 (3H, t,
J = 7.3), 1.30 (3H, t, J = 7.1), 1.37 (2H, m), 1.59 (2H, quint, J = 7.6),
2.89 (2H, t, J = 7.6), 4.20 (2H, q, J = 7.1), 5.91 (1H, br s), 8.11 (1H,
dd, J = 15.1, 8.7), 10.31 (1H, br s); 13C NMR (CDCl3) d 14.0, 14.4,
22.6, 27.1, 42.2, 59.6, 101.8, 158.1, 167.2, 203.2. HRMS (ESI): for
C
27H30NO3 calcd: 416.2226 [MH]+; found: 416.2225.
5.62. Ethyl (2E)-2-pentanoyl-3-{[4-(pyridin-4-ylmethyl)
phenyl]amino}acrylate (59)
The title compound was prepared and purified according to the
procedure described for 41, but using 38 instead of 4-ethylaniline.
C
10H18NO3 calcd: 200.1287 [MH]+; found: 200.1289.