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D. Merk et al. / Bioorg. Med. Chem. 22 (2014) 2447–2460
acetate 1:1 + 2% acetic acid) = 0.43. 1H NMR (500 MHz, DMSO) d
12.70 (s, 1H), 8.98 (s, 1H), 8.68 (dd, J = 8.3, 0.8 Hz, 1H), 8.55 (d,
J = 0.9 Hz, 1H), 8.12 (d, J = 8.3 Hz, 2H), 8.03 (t, J = 6.0 Hz, 1H), 7.99
(dd, J = 8.6, 1.8 Hz, 1H), 7.86 (dd, J = 7.9, 1.2 Hz, 1H), 7.70–7.56
(m, 4H), 7.25–7.20 (m, 1H), 3.29–3.23 (m, 2H), 2.32 (t, J = 7.3 Hz,
2H), 1.80 (p, J = 7.1 Hz, 2H). 13C NMR (126 MHz, DMSO) d 174.80,
169.15, 164.96, 139.87, 134.90, 132.73, 132.66, 132.43, 129.63,
129.19, 128.73, 128.62, 128.31, 128.19, 127.57, 123.71, 123.37,
120.99, 120.86, 39.30, 31.76, 24.69. C22H20N2O4. MS (ESIꢀ): m/z
375.21 ((MꢀH)ꢀ, 100). Combustion analysis: measured (calcu-
lated): C 69.95 (70.20); H 5.44 (5.36); N 7.12 (7.44).
2H), 1.78 (p, J = 7.2 Hz, 2H). 13C NMR (126 MHz, DMSO) d 174.72,
168.74, 164.11, 134.97, 132.22, 131.64, 130.43, 129.41, 128.64,
128.58, 123.24, 123.04, 122.95, 70.26, 68.35, 31.57, 31.17, 24.73.
C20H20N2O4. MS (MALDI): m/z 352.9 ((M+1), 100). Combustion
analysis: measured (calculated): C 67.90 (68.17); H 5.88 (5.72); N
8.14 (7.95).
5.1.1.15. 4-(2-(3-Phenylpropanamido)benzamido)butanoic acid
(15o).
Preparation according to general procedure b using 6a
and 3-phenylpropanoyl chloride (8o). Yield 71.2%. Rf (pentane/
ethyl acetate 1:1 + 2% acetic acid) = 0.41. 1H NMR (500 MHz,
DMSO) d 12.06 (s, 1H), 11.25 (s, 1H), 8.73 (t, J = 5.4 Hz, 1H), 8.36
(d, J = 8.2 Hz, 1H), 7.69 (dd, J = 7.9, 1.3 Hz, 1H), 7.48–7.44 (m, 1H),
7.29–7.22 (m, 3H), 7.17 (ddd, J = 8.5, 6.4, 4.0 Hz, 2H), 7.12 (td,
J = 7.8, 1.1 Hz, 1H), 3.27 (dd, J = 12.7, 6.8 Hz, 2H), 2.92 (t,
J = 7.6 Hz, 2H), 2.66 (t, J = 7.7 Hz, 2H), 2.29 (t, J = 7.3 Hz, 2H), 1.75
(p, J = 7.2 Hz, 2H). 13C NMR (126 MHz, DMSO) d 174.71, 170.61,
168.71, 141.23, 139.18, 135.58, 132.19, 130.90, 128.78, 128.72,
126.47, 122.99, 46.07, 39.07, 33.17, 31.60, 31.08, 24.71.
5.1.1.11.
(15k).
4-(2-(1-Naphthamido)benzamido)butanoic
Preparation according to general procedure b using
acid
6a and 1-naphthoyl chloride (8k). Yield 58.7%. Rf (pentane/ethyl
acetate 1:1 + 2% acetic acid) = 0.43. 1H NMR (500 MHz, DMSO) d
12.09 (s, 1H), 8.85 (t, J = 5.5 Hz, 1H), 8.66 (d, J = 8.2 Hz, 1H), 8.38–
8.34 (m, 1H), 8.12 (d, J = 8.3 Hz, 1H), 8.06–8.02 (m, 1H), 7.85 (dd,
J = 7.1, 1.1 Hz, 1H), 7.82 (dd, J = 7.9, 1.4 Hz, 1H), 7.66–7.59 (m,
4H), 7.24 (td, J = 7.7, 1.2 Hz, 1H), 3.23 (dd, J = 12.6, 6.9 Hz, 2H),
2.26 (t, J = 7.3 Hz, 2H), 1.73 (p, J = 7.2 Hz, 2H). 13C NMR
C
20H22N2O4. MS (ESIꢀ): m/z 353.4 ((MꢀH)ꢀ, 100). Combustion
analysis: measured (calculated): C 68.12 (67.78); H 6.33 (6.26); N
7.50 (7.90).
(125 MHz, DMSO)
d 173.77, 167.83, 166.18, 138.37, 133.57,
132.67, 131.32, 130.23, 128.87, 127.71, 127.48, 126.46, 125.81,
124.55, 124.45, 124.37, 122.40, 120.44, 119.83, 29.77, 29.37,
22.78. C22H20N2O4. MS (ESIꢀ): m/z 375.20 ((MꢀH)ꢀ, 100). Combus-
tion analysis: measured (calculated): C 70.11 (70.20); H 5.59
(5.36); N 7.09 (7.44).
5.1.1.16. 4-(2-(2-(Naphthalen-2-yl)acetamido)benzamido)buta-
noic acid (15p).
Preparation according to general procedure b
using 6a and 2-(naphthalen-2-yl)acetyl chloride (8p). Yield 65.0%.
Rf (pentane/ethyl acetate 1:1 + 2% acetic acid) = 0.48. 1H NMR
(500 MHz, DMSO) d 11.30 (s, 1H), 8.71 (s, 1H), 8.34 (d, J = 8.3 Hz,
1H), 7.94–7.83 (m, 4H), 7.66 (d, J = 7.6 Hz, 1H), 7.55–7.42 (m,
4H), 7.12 (t, J = 7.5 Hz, 1H), 3.86 (s, 2H), 3.20 (q, J = 6.3 Hz, 2H),
2.25 (t, J = 7.2 Hz, 2H), 1.70 (p, J = 6.9 Hz, 2H). 13C NMR (126 MHz,
DMSO) d 174.74, 169.58, 168.56, 139.01, 133.55, 133.37, 132.43,
132.10, 128.45, 128.42, 128.32, 128.14, 127.97, 126.63, 126.19,
123.21, 122.09, 120.96, 45.03, 39.06, 31.61, 24.67. C23H22N2O4.
MS (ESIꢀ): m/z 389.21 ((MꢀH)ꢀ, 100). Combustion analysis: mea-
sured (calculated): C 70.51 (70.75); H 5.63 (5.68); N 6.92 (7.17).
5.1.1.12. 4-(2-(2,2-Diphenylacetamido)benzamido)butanoic acid
(15l).
Preparation according to general procedure b using 6a
and 2,2-diphenylacetyl chloride (8 l). Yield 64.8%. Rf (pentane/ethyl
acetate 1:1 + 2% acetic acid) = 0.42. 1H NMR (500 MHz, DMSO) d
12.69 (s, 1H), 11.39 (s, 1H), 8.70 (s, 1H), 8.36 (d, J = 8.0 Hz, 1H),
7.66 (dd, J = 7.9, 1.4 Hz, 1H), 7.50–7.45 (m, 1H), 7.40–7.31 (m, 8H),
7.28–7.23 (m, 2H), 7.14 (t, J = 7.5 Hz, 1H), 5.19 (s, 1H), 3.20 (dd,
J = 12.6, 6.8 Hz, 2H), 2.37–2.30 (m, 2H), 1.72 (p, J = 7.2 Hz, 2H). 13C
NMR (125 MHz, DMSO) d 172.65, 169.58, 167.56, 138.89, 137.71,
130.95, 127.93, 127.71, 127.26, 126.19, 122.19, 121.05, 119.97,
50.07, 37.14, 29.40, 29.36, 22.75. C25H24N2O4. MS (ESIꢀ): m/z
415.26 ((MꢀH)ꢀ, 100). Combustion analysis: measured (calcu-
lated): C 71.97 (72.10); H 6.08 (5.81); N 6.92 (6.73).
5.1.1.17. Methyl 4-(2-(2-naphthamido)benzamido)butanoate
(16).
Preparation according to general procedure b using 6b
and 2-naphthoyl chloride (8j). Yield 74.0%. Rf (pentane/ethyl ace-
tate 1:1 + 2% acetic acid) = 0.62. 1H NMR (500 MHz, DMSO) d
12.66 (s, 1H), 8.93 (t, J = 5.4 Hz, 1H), 8.67 (d, J = 7.7 Hz, 1H), 8.55
(s, 1H), 8.12 (t, J = 8.4 Hz, 2H), 8.04 (d, J = 7.8 Hz, 1H), 7.99 (dd,
J = 8.6, 1.6 Hz, 1H), 7.88–7.83 (m, 1H), 7.66 (qd, J = 6.9, 3.4 Hz,
2H), 7.63–7.58 (m, 1H), 7.27–7.20 (m, 1H), 3.55 (s, 3H), 3.39–
3.35 (t, J = 7.0 Hz, 2H), 2.42 (t, J = 7.3 Hz, 2H), 1.84 (p, J = 7.1 Hz,
2H). 13C NMR (126 MHz, DMSO) d 173.60, 169.17, 164.97, 139.82,
134.90, 132.74, 132.69, 132.43, 129.60, 129.17, 128.71, 128.61,
128.31, 128.19, 127.57, 123.70, 123.39, 121.07, 120.96, 51.71,
39.06, 31.22, 24.62. C23H22N2O4. MS (ESI+): m/z 391.24 ((M+H)+,
5.1.1.13. 4-(2-(3,3-Diphenylpropanamido)benzamido)butanoic
acid (15m).
Preparation according to general procedure b
using 6a and 3,3-diphenylpropanoyl chloride (8m). Yield 68.3%.
Rf (pentane/ethyl acetate 1:1 + 2% acetic acid) = 0.44. 1H NMR
(500 MHz, DMSO) d 12.13 (s, 1H), 11.28 (s, 1H), 8.71 (t, J = 5.4 Hz,
1H), 8.24 (d, J = 8.3 Hz, 1H), 7.66 (d, J = 7.9 Hz, 1H), 7.44–7.38 (m,
1H), 7.35 (d, J = 7.4 Hz, 4H), 7.26 (dd, J = 10.5, 4.9 Hz, 4H), 7.18–
7.12 (m, 2H), 7.09 (td, J = 7.7, 1.1 Hz, 1H), 4.53 (t, J = 7.9 Hz, 1H),
3.32–3.28 (m, 2H), 3.15 (d, J = 8.0 Hz, 2H), 2.31 (t, J = 7.2 Hz, 2H),
1.78 (p, J = 7.0 Hz, 2H). 13C NMR (125 MHz, DMSO) d 173.81,
168.57, 167.70, 143.40, 137.88, 130.92, 127.68, 127.24, 126.81,
125.48, 121.77, 120.35, 119.68, 45.65, 41.78, 37.32, 29.77, 22.91.
100). Combustion analysis: measured (calculated):
(70.75); H 5.68 (5.68); N 7.08 (7.17).
C
70.51
5.1.1.18.
5-(2-(2-Naphthamido)benzamido)pentanoic
acid
C
26H26N2O4. MS (ESIꢀ): m/z 429.26 ((MꢀH)ꢀ, 100). Combustion
(17). Preparation according to general procedure b using 6c
analysis: measured (calculated): C 72.72 (72.54); H 5.98 (6.09); N
6.22 (6.51).
and 2-naphthoyl chloride (8j). Yield 58.2%. Rf (pentane/ethyl ace-
tate 1:1 + 2% acetic acid) = 0.46. 1H NMR (500 MHz, DMSO) d
12.72 (s, 1H), 8.92 (t, J = 5.5 Hz, 1H), 8.69 (dd, J = 8.4, 1.0 Hz, 1H),
8.55 (d, J = 1.1 Hz, 1H), 8.13 (d, J = 8.2 Hz, 2H), 8.04 (d, J = 7.7 Hz,
1H), 7.99 (dd, J = 8.6, 1.8 Hz, 1H), 7.86 (dd, J = 8.0, 1.3 Hz, 1H),
7.70–7.62 (m, 2H), 7.62–7.58 (m, 1H), 7.23 (td, J = 7.9, 1.2 Hz,
1H), 3.32 (d, J = 3.6 Hz, 2H), 2.26 (t, J = 6.9 Hz, 2H), 1.58 (dt,
J = 6.9, 3.6 Hz, 4H). 13C NMR (125 MHz, DMSO) d 173.95, 168.06,
163.97, 138.74, 133.73, 131.55, 131.48, 131.25, 128.42, 128.00,
127.47, 127.41, 127.10, 126.98, 126.36, 122.45, 122.13, 119.73,
119.62, 37.63, 31.95, 26.97, 20.60. C23H22N2O4. MS (ESIꢀ): m/z
5.1.1.14.
(15n).
4-(2-Cinnamamidobenzamido)butanoic
Preparation according to general procedure b using
acid
6a and cinnamoyl chloride (8n). Yield 50.2%. Rf (pentane/ethyl ace-
tate 1:1 + 2% acetic acid) = 0.42. 1H NMR (500 MHz, DMSO) d 12.10
(s, 1H), 11.51 (s, 1H), 8.79 (t, J = 5.6 Hz, 1H), 8.59 (d, J = 7.5 Hz, 2H),
8.50 (t, J = 8.8 Hz, 1H), 8.01 (dd, J = 7.9, 1.6 Hz, 2H), 7.57–7.50 (m,
2H), 7.20–7.15 (m, 1H), 7.13 (t, J = 7.4 Hz, 1H), 6.86 (d, J = 1.7 Hz,
1H), 6.82 (d, J = 1.6 Hz, 1H), 3.28–3.24 (m, 2H), 2.30 (t, J = 7.3 Hz,