Organic & Biomolecular Chemistry
Paper
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180–182 °C; EI-MS (m/z) 522[M]+; H NMR (400 MHz, DMSO- bonyl]pyridin-3-yl}benzoic acid (6d) and 1.35 g 1-[3-(trifluoro-
d6) δ 9.06 (s, 1H), 8.98 (d, J = 1.5 Hz, 1H), 8.74 (d, J = 3.8 Hz, methyl)benzoyl]piperazine (7I). Elution with petroleum ether/
1H), 8.45 (d, J = 2.0 Hz, 1H), 7.90 (d, J = 8.2 Hz, 2H), 7.86 (d, J = ethyl acetate (1/5, v/v) gave a solid (0.49 g, 26%). Mp
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7.6 Hz, 1H), 7.80 (s, 1H), 7.74 (dd, J = 15.9, 7.1 Hz, 1H), 7.59 (d, 125–127 °C; EI-MS (m/z) 538[M]+; H NMR (400 MHz, DMSO-
J = 8.1 Hz, 2H), 3.84–3.38 (m, 8H), 2.90 (dd, J = 7.3, 3.4 Hz, d6) δ 9.01 (s, 1H), 8.59 (s, 1H), 8.13 (s, 1H), 7.90 (d, J = 7.7 Hz,
1H), 0.80–0.72 (m, 2H), 0.66–0.58 (m, 2H); 13C NMR (101 MHz, 2H), 7.86 (d, J = 7.8 Hz, 1H), 7.80 (s, 1H), 7.75 (s, 1H), 7.72 (d, J
DMSO-d6) δ 169.31, 168.19, 166.24, 150.20, 148.22, 138.10, = 7.8 Hz, 1H), 7.57 (d, J = 7.1 Hz, 2H), 3.42–3.71 (m, 8H), 3.49
137.20, 135.98, 134.70, 133.19, 131.49, 130.33, 130.18, 128.41, (d, J = 4.0 Hz, 2H), 3.24 (d, J = 8.0 Hz, 2H), 1.15 (d, J = 47.4 Hz,
127.61, 126.82, 126.79, 125.69, 124.30, 124.26, 122.98, 47.43, 6H); 13C NMR (101 MHz, DMSO-d6) δ 169.30, 168.18, 167.84,
42.19, 23.53, 6.23.
148.50, 146.44, 137.95, 137.20, 135.97, 134.83, 133.70, 132.26,
N-Cyclopropyl-5-(4-{[4-(3,4-difluorobenzoyl)piperazin-1-yl] 131.49, 130.18, 128.41, 127.62, 126.82, 126.78, 125.69, 124.30,
carbonyl}phenyl)nicotinamide (10i). The procedure described 124.26, 122.98, 47.64, 43.49, 42.13, 14.53, 13.29.
above was used with 0.99 g 4-{5-[(cyclopropylamino)carbonyl]-
5-[4-({4-[4-Chloro-3-(trifluoromethyl)benzoyl]piperazin-1-yl}
pyridin-3-yl}benzoic acid (6c) and 1.18 1-(3,4-difluoro- carbonyl)phenyl]-N,N-diethylnicotinamide (10m). The pro-
g
benzoyl)piperazine (7III). Elution with petroleum ether/ethyl cedure described above was used with 1.04 g 4-{5-[(diethyl-
acetate (1/5, v/v) gave a solid (0.41 g, 24%). Mp 221–222 °C; amino)carbonyl]pyridin-3-yl}benzoic acid (6d) and 1.50 g 1-[4-
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EI-MS (m/z) 490[M]+; H NMR (400 MHz, DMSO-d6) δ 8.98 (s, chloro-3-(trifluoromethyl)benzoyl]piperazine (7II). Elution with
1H), 8.75 (d, J = 3.1 Hz, 1H), 8.45 (s, 1H), 7.90 (d, J = 7.7 Hz, petroleum ether/ethyl acetate (1/5, v/v) gave a solid (0.46 g,
2H), 7.59 (d, J = 7.6 Hz, 4H), 7.39–7.28 (m, 1H), 3.44–3.66 (m, 23%). Mp 149–151 °C; EI-MS (m/z) 572[M]+; 1H NMR
8H), 1.21 (s, 1H), 0.75 (d, J = 6.3 Hz, 2H), 0.61 (d, J = 4.0 Hz, (400 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.59 (d, J = 1.8 Hz, 1H),
2H); 13C NMR (101 MHz, DMSO-d6) δ 169.29, 167.52, 166.24, 8.13 (d, J = 1.6 Hz, 1H), 7.91 (s, 2H), 7.89 (s, 1H), 7.81 (dd, J =
150.20, 148.22, 138.11, 135.96, 134.69, 133.20, 130.33, 128.41, 25.5, 7.8 Hz, 2H), 7.57 (d, J = 7.9 Hz, 2H), 3.43–3.68 (m, 8H),
127.61, 124.87, 118.39, 118.22, 117.36, 117.18, 47.63, 42.35, 3.49 (d, J = 6.5 Hz, 2H), 3.24 (d, J = 6.5 Hz, 2H), 1.19 (s, 3H),
23.53, 6.23.
N-Cyclopropyl-5-[4-({4-[3-(dimethylamino)benzoyl]piperazin- 167.27, 148.50, 146.44, 137.96, 135.96, 135.67, 134.82, 133.70,
1-yl}carbonyl)phenyl]nicotinamide (10j). The procedure 133.16, 132.36, 132.26, 128.40, 127.62, 127.22, 126.90, 124.37,
1.09 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 169.30, 167.84,
described above was used with 0.99 g 4-{5-[(cyclopropylamino)- 121.69, 118.94, 47.41, 43.48, 42.13, 41.70, 14.52, 13.27; HRMS
carbonyl]pyridin-3-yl}benzoic acid (6c) and 1.22 g dimethyl- (ESI): calcd for [M + Na]+ C29H28ClF3N4O3Na: 595.1700, found
[3-(piperazin-1-ylcarbonyl)phenyl]amine (7VI). Elution with pet- 595.1690.
roleum ether/ethyl acetate (1/7, v/v) gave a solid (0.36 g, 21%).
5-[4-({4-[4-(Dimethylamino)benzoyl]piperazin-1-yl}carbonyl)
(10n). The procedure
Mp 184–186 °C; EI-MS (m/z) 497[M]+; 1H NMR (400 MHz, phenyl]-N,N-diethylnicotinamide
DMSO-d6) δ 9.06 (s, 1H), 8.98 (s, 1H), 8.74 (d, J = 3.8 Hz, 1H), described above was used with 1.04 g 4-{5-[(diethylamino)car-
8.45 (s, 1H), 7.90 (d, J = 7.6 Hz, 2H), 7.59 (d, J = 8.0 Hz, 2H), bonyl]pyridin-3-yl}benzoic acid (6d) and 1.22 g dimethyl-
7.24 (t, J = 7.8 Hz, 1H), 6.79 (d, J = 7.4 Hz, 1H), 6.69 (s, 1H), [3-(piperazin-1-ylcarbonyl)phenyl]amine (7VI). Elution with pet-
6.66 (d, J = 7.3 Hz, 1H), 3.46–3.66 (m, 8H), 2.92 (s, 6H); 13C roleum ether/ethyl acetate (1/7, v/v) gave a solid (0.39 g, 22%).
NMR (101 MHz, DMSO-d6) δ 170.39, 169.28, 166.25, 150.65, Mp 157–158 °C; EI-MS (m/z) 513[M]+; 1H NMR (400 MHz,
150.20, 148.21, 138.05, 136.82, 136.03, 134.71, 133.18, 130.33, DMSO-d6) δ 9.01 (s, 1H), 8.59 (d, J = 1.4 Hz, 1H), 8.13 (s, 1H),
129.43, 128.42, 127.60, 114.59, 113.70, 110.83, 47.56, 42.19, 7.89 (d, J = 7.7 Hz, 2H), 7.57 (d, J = 7.9 Hz, 2H), 7.24 (t, J =
40.45, 23.54, 6.24.
7.5 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 6.69 (s, 1H), 6.66 (d, J =
N-Cyclopropyl-5-(4-{[4-(2,4-dichlorobenzoyl)piperazin-1-yl] 7.3 Hz, 1H), 3.36–3.66 (m, 8H), 3.49 (d, J = 5.9 Hz, 2H), 3.24 (d,
carbonyl}phenyl)nicotinamide (10k). The procedure described J = 5.9 Hz, 2H), 2.92 (s, 6H), 1.19 (t, J = 4.0 Hz, 3H), 1.09 (s,
above was used with 0.99 g 4-{5-[(cyclopropylamino)carbonyl]- 3H); 13C NMR (101 MHz, DMSO-d6) δ 170.38, 169.27, 167.85,
pyridin-3-yl}benzoic acid (6c) and 1.36 g 1-(2,4-dichloroben- 150.65, 148.50, 146.44, 137.92, 136.84, 136.03, 134.84, 133.70,
zoyl)piperazine (7VII). Elution with petroleum ether/ethyl 132.27, 129.42, 128.43, 127.60, 114.61, 113.69, 110.85, 47.52,
acetate (1/5, v/v) gave a solid (0.44 g, 24%). Mp 183–185 °C; 43.50, 42.26, 40.44, 14.54, 13.29.
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EI-MS (m/z) 522[M]+; H NMR (400 MHz, DMSO-d6) δ 8.98 (s,
N-Isopropyl-5-[4-({4-[3-(trifluoromethyl)benzoyl]piperazin-1-
1H), 8.74 (d, J = 3.5 Hz, 1H), 8.45 (s, 1H), 7.89 (d, J = 6.3 Hz, yl} carbonyl)phenyl]nicotinamide (10o). The procedure
2H), 7.75 (s, 1H), 7.60 (d, J = 7.5 Hz, 2H), 7.58–7.51 (m, 1H), described above was used with 1.00 g 4-{5-[(isopropylamino)-
7.47 (d, J = 8.0 Hz, 1H), 3.26–3.73 (m, 8H), 2.96–2.85 (m, 1H), carbonyl]pyridin-3-yl}benzoic acid (6e) and 1.35 g 1-[3-(trifluor-
0.75 (q, J = 6.6 Hz, 2H), 0.62 (d, J = 2.4 Hz, 2H); 13C NMR omethyl)benzoyl]piperazine (7I). Elution with petroleum ether/
(101 MHz, DMSO-d6) δ 169.31, 166.24, 165.42, 150.20, 148.23, ethyl acetate (1/5, v/v) gave a solid (0.49 g, 27%). Mp
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138.11, 135.91, 134.86, 134.69, 133.19, 130.86, 130.32, 129.89, 225–227 °C; EI-MS (m/z) 524[M]+; H NMR (400 MHz, DMSO-
129.58, 128.44, 127.59, 46.65, 41.74, 23.54, 6.24.
d6) δ 9.06 (s, 1H), 9.01 (d, J = 1.6 Hz, 1H), 8.54 (d, J = 7.6 Hz,
N,N-Diethyl-5-[4-({4-[3-(trifluoromethyl)benzoyl]piperazin-1- 1H), 8.48 (d, J = 2.0 Hz, 1H), 7.91 (d, J = 8.1 Hz, 2H), 7.86 (d, J =
yl} carbonyl)phenyl]nicotinamide (10l). The procedure 7.0 Hz, 1H), 7.80 (s, 1H), 7.74 (dd, J = 16.3, 7.3 Hz, 2H), 7.60 (d,
described above was used with 1.04 g 4-{5-[(diethylamino)car- J = 7.9 Hz, 2H), 4.15 (dd, J = 13.7, 6.8 Hz, 1H), 3.84–3.39 (m,
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Org. Biomol. Chem., 2015, 13, 7050–7066 | 7063