The Journal of Organic Chemistry
Note
135.0, 135.7, 137.2, 140.4, 167.6. MS (EI) m/z: (%) 345 (28, [M+]),
299 (37), 229 (77), 230 (100),215 (38). HRMS (EI) m/z: Calcd for
C17H1635ClN3O3 [M+] 345.0880; Found 345.0880.
N-(5-Methoxy-2-nitrophenyl)-N-[2-(morpholin-4-ylcarbonyl)-
phenyl]amine (3j). Yellow crystals, mp 186−188 °C (toluene/
hexane), 990 mg, 96% yield. 1H NMR (500 MHz, CDCl3) δ 3.41 (br
s, 2H), 3.53 (br s, 2H), 3.62−3.75 (m, 4H), 3.76 (s, 3H), 6.38 (dd, J
= 9.5, 2.6 Hz, 1H), 6.59 (d, J = 2.6 Hz, 1H), 7.26 (td, J = 7.3, 1.5 Hz,
1H), 7.38 (dd, J = 7.6, 1.0 Hz, 1H), 7.41−7.48 (m, 2H), 8.18 (d, J =
9.5, 1H), 9.90 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 42.2,
47.6, 55.8, 66.7, 98.2, 106.9, 124.4, 125.6, 128.1, 128.5, 129.1, 130.4,
131.0, 135.8, 144.3, 165.5, 167.9. MS (EI) m/z: (%) 357 (43, [M+]),
311 (45), 225 (100), 224 (77), 211 (45), 196 (55). HRMS (EI) m/z:
Calcd for C18H19N3O5 [M+] 357.1325; Found 357.1326.
N-(5-Chloro-2-nitrophenyl)-N-[2-(morpholin-4-ylcarbonyl)-
phenyl]amine (3k). Orange crystals, mp 153−154 °C (EtOAc/
MeOH), 846 mg, 78% yield. 1H NMR (500 MHz, CDCl3) δ 3.41 (br
s, 2H), 3.51−3.85 (m, 6H), 6.79 (dd, J = 9.0, 2.1 Hz, 1H), 7.24 (d, J =
2.1, Hz, 1H), 7.26−7.31 (m, 1H), 7.36−7.39 (m, 1H), 7.45−7.49 (m,
2H), 8.16 (d, J = 9.0 Hz, 1H), 9.87 (s, 1H). 13C{1H} NMR (125
MHz, CDCl3) δ 42.3, 47.8, 66.8, 115.5, 118.7, 124.1, 125.6, 128.2,
128.4, 130.4, 130.6, 132.6, 136.0, 142.2, 142,5, 167.7. MS (EI) m/z:
(%) 363 (16), 361 (41, [M+]), 317 (19), 315 (44), 231 (52), 229
(100). HRMS (EI) m/z: Calcd for C17H1635ClN3O4 [M+] 361.0829;
Found 361.0829.
N-(5-Chloro-2-nitrophenyl)-N-{2-[(4-methylpiperazin-1-yl)-
carbonyl]phenyl}amine (3l). Orange crystals, mp 120−124 °C
(EtOAc/hexane), 1120 mg, 99% yield. 1H NMR (500 MHz,
CDCl3) δ 2.27 (s, 3H), 2.24−3.34 (m, 2H), 2.41 (br s, 2H), 3.39
(br s, 2H), 3.37 (br s, 2H), 6.76 (dd J = 9.0, 2.1 Hz, 1H), 7.22 (d, J =
2.1 Hz, 1H), 7.25−7.29 (m, 1H), 7.35−7.38 (m, 1H), 7.43−7.65 (m,
2H), 8.15 (d, J = 9.0 Hz, 1H), 9.82 (s, 1H). 13C{1H} NMR (125
MHz, CDCl3) δ 41.8, 46.0, 47.2, 54.6, 55.1, 115.6, 118.6, 124.3, 125.7,
128.1, 128.3, 130.4, 131.0, 132.5, 135.8, 142.2, 142.7, 167.5. MS (EI)
m/z: (%) 376 (16), 374 (41, [M+]), 231 (22), 229 (45), 99 (51), 70
(100). HRMS (EI) m/z: Calcd for C18H1935ClN4O3 [M+] 374.1146;
Found 374.1149.
N-{2-[(4-Methylpiperazin-1-yl)carbonyl]phenyl}-N-[2-nitro-4-
(trifluoromethyl)phenyl]amine (3d). Eluent: EtOAc. Orange precip-
itate, mp 103−105 °C, 1.03 g, 86% yield. 1H NMR (500 MHz,
CD2Cl2) δ 2.22−2.29 (m, 5H), 2.39 (br s, 2H), 3.39 (br s, 2H), 3.72
(br s, 2H), 7.31−7.35 (m, 1H), 7.36−7.42 (m, 2H), 7.48−7.51 (m,
2H), 7.61 (dd, J = 9.0, 1.9 Hz, 1H), 8.51 (d, J = 1.2 Hz, 1H), 10.06
(br s, 1H). 13C{1H} NMR (125 MHz, CD2Cl2) δ 41.7, 45.6, 47.3,
54.5, 55.1, 117.1, 119.5 (q, JFC = 34 Hz), 123.5 (q, JFC = 271 Hz),
124.5, 124.6 (q, JFC = 4.2 Hz), 125.8, 128.2, 130.3, 131.2, 131.5 (q,
J
FC = 3.3 Hz), 132.9, 135.7, 144.2, 167.2. MS (EI) m/z: (%) 408 (50,
[M+]), 263 (53), 99 (45), 70 (100). HRMS (EI) m/z: Calcd for
C19H19F3N4O3 [M+] 408.1409; Found 408.1407.
N-[2-(Morpholin-4-ylcarbonyl)phenyl]-N-[2-nitro-4-
(trifluoromethyl)phenyl]amine (3e). Eluent: hexane/EtOAc from 9:1
1
to 2:1. Orange precipitate, mp 108−111 °C, 789 mg, 67% yield. H
NMR (600 MHz, CD2Cl2) δ 3.35−3.75 (m, 8H), 7.31−7.34 (m, 1H),
7.37−7.41 (m, 2H), 7.47−7.52 (m, 2H), 7.60 (dd, J = 8.8, 2.1 Hz,
1H), 8.50 (d, J = 1.2 Hz, 1H), 10.09 (br s, 1H). 13C{1H} NMR (150
MHz, CD2Cl2) δ 42.6, 48.3, 67.1, 117.5, 120.1 (q, JFC = 34 Hz), 123.9
(q, JFC = 271 Hz), 124.8, 125.0 (q, JFC = 4 Hz), 126.2, 128.7, 130.9,
131.0, 131.9 (q, JFC = 3 Hz), 133.4, 136.2, 144.4, 167.8. MS (EI) m/z:
(%) 395 (36, [M+]), 376 (10), 349 (30), 263 (100), 262 (72). HRMS
(EI) m/z: Calcd for C18H16F3N3O4 [M+] 395.1093; Found 395.1096.
N-[2-(Morpholin-4-ylcarbonyl)phenyl]-N-(2-nitrophenyl)amine
1
(3f). Orange precipitate, mp 111−112 °C, 930 mg, 95% yield. H
NMR (500 MHz, CDCl3) δ 3.31−3.93 (m, 8H), 6.84 (ddd, J = 8.5,
7.0, 1.2 Hz, 1H), 7.23 (td, J = 7.5, 1.2 Hz, 1H), 7.28 (dd, J = 8.7, 1.0
Hz, 1H), 7.36 (dd, J = 7.5, 1.2 Hz, 1H), 7.38−7.44 (m, 2H), 7.47 (d, J
= 8.0 Hz, 1H), 8.20 (dd, J = 8.7, 1.5 Hz, 1H), 9.73 (s, 1H). 13C{1H}
NMR (125 MHz, CDCl3) δ 42.3, 47.7, 66.8, 116.4, 118.5, 123.7,
125.0, 126.7, 128.3, 130.2, 130.4, 134.3, 135.5, 136.5, 141.6, 168.0.
MS (EI) m/z: (%) 327 (44, [M+]), 281 (30), 195 (100). HRMS (EI)
m/z: Calcd for C17H17N3O4 [M+] 327.1219; Found 327.1224.
N-{2-[(4-Methylpiperazin-1-yl)carbonyl]phenyl}-N-(2-
nitrophenyl)amine (3g). Red crystals, mp 114−115 °C (EtOAc/
hexane), 878 mg, 86% yield. 1H NMR (500 MHz, CDCl3) δ 2.32 (s,
3H), 2.30−2.55 (m, 4H), 3.44 (br s, 2H), 3.81 (br s, 2H), 6.83 (ddd,
J = 8.3, 6.9, 1.0 Hz, 1H), 7.23 (td, J = 7.6, 1.2 Hz, 1H), 7.28 (td, J =
8.7, 1.0 Hz, 1H), 7.36 (dd, J = 7.6, 1.5 Hz, 1H), 7.37−7.44 (m, 2H),
7.46 (d, J = 7.7 Hz, 1H), 8.19 (dd, J = 8.3, 1.5 Hz, 1H), 9.69 (s, 1H).
13C{1H} NMR (125 MHz, CDCl3) δ 41.4, 45.7, 46.8, 54.4, 54.9,
N-(5-Chloro-2-nitrophenyl)-N-[2-(pyrrolidin-1-ylcarbonyl)-
phenyl]amine (3m). Brown crystals, mp 141−142 °C (EtOAc/
1
hexane), 1059 mg, 97% yield. H NMR (500 MHz, CDCl3) δ 1.85−
2.00 (m, 4H), 3.35−3.65 (m, 4H), 6.77 (dd, J = 9.0, 2.1 Hz, 1H), 7.23
(td, J = 7.3, 1.0 Hz, 1H), 7.33 (d, J = 2.1 Hz, 1H), 7.41−7.50 (m,
3H), 8.15 (d, J = 9.0 Hz, 1H), 10.13 (s, 1H). 13C{1H} NMR (125
MHz, CDCl3) δ 24.4, 26.1, 45.9, 49.1, 115.9, 118.5, 123.1, 124.9,
128.1, 128.3, 130.4, 131.3, 132.9, 136.1, 142.0, 142.3, 167.3. MS (EI)
m/z: (%) 347 (15), 345 (42, [M+]), 299 (61), 229 (100), 215 (59),
200 (57). HRMS (EI) m/z: Calcd for C17H1635ClN3O3 [M+]
345.0880; Found 345.0883.
116.5, 118.4, 123.9, 125.1, 126.7, 128.3, 130.3, 130.5, 134.3, 135.5,
136.4, 141.8, 167.8. MS (EI) m/z: (%) 340 (61, [M+]), 194 (66), 99
(52), 70 (100). HRMS (EI) m/z: Calcd for C18H20N4O3 [M+]
340.1535; Found 340.1551.
N-(2-Nitrophenyl)-N-[2-(pyrrolidin-1-ylcarbonyl)phenyl]amine
(3h). Red crystals, mp 117−120 °C (EtOAc/hexane), 805 mg, 86%
yield. 1H NMR (500 MHz, CDCl3) δ 1.91 (br s, 4H), 3.22−3.71 (m,
4H), 6.82 (ddd, J = 8.4, 6.4, 1.7 Hz, 1H), 7.18 (t, J = 7.4 Hz, 1H),
7.35−7.44 (m, 4H), 7.46 (d, J = 8.0 Hz, 1H), 8.18 (d, J = 8.4 Hz,
1H), 9.96 (br s, 1H). 13C{1H} NMR (125 MHz, CDCl3) δ 24.6, 26.0,
46.0, 49.0, 116.8, 118.3, 122.8, 124.3, 126.6, 128.1, 130.1, 131.2,
134.6, 135.3, 136.6, 141.4, 167.7. MS (EI) m/z: (%) 311 (50, [M+]),
265 (51), 195 (100). HRMS (EI) m/z: Calcd for C17H17N3O3 [M+]
311.1270; Found 311.1266.
2-[(5-Chloro-2-nitrophenyl)amino]-N,N-dimethylbenzamide
(3n). Yellow solid, mp 96−98 °C, 423 mg, 88% yield. 1H NMR (600
MHz, DMSO-d6) δ 2.91 (s, 3H), 2.93 (s, 3H), 6.94 (dd, J = 9.1, 2.2
Hz, 1H), 7.18 (d, J = 2.2 Hz, 1H), 7.31 (td, J = 7.6, 1.2 Hz, 1H), 7.45
(dd, J = 7.6, 1.2 Hz, 1H), 7.49−7.56 (m, 2H), 8.15 (d, J = 9.1 Hz,
1H), 9.83 (s, 1H). 13C{1H} NMR (150 MHz, DMSO-d6) δ 34.8,
39.1, 116.3, 118.9, 124.5, 125.6, 128.70, 128.73, 130.8, 131.2, 132.9,
136.3, 141.2, 142.5, 168.4. MS (EI) m/z: (%) 321 (23), 319 (57,
[M+]), 273 (63), 229 (95), 228 (100), 200 (58). HRMS (EI) m/z:
Calcd for C15H1435ClN3O3 [M+] 319.0724; Found 319.0718.
N-Butyl-2-[(5-chloro-2-nitrophenyl)amino]benzamide (3o). Yel-
1
low powder, mp 129−130 °C, 499 mg, 96% yield. H NMR (600
MHz, DMSO-d6) δ 0.86 (t, J = 7.4 Hz, 3H), 1.29 (sext, J = 7.4 Hz,
2H), 1.45 (quin, J = 7.3 Hz, 2H), 3.22 (q, J = 7.0 Hz, 2H), 6.98 (dd, J
= 9.1, 2.2 Hz, 1H), 7.24 (td, J = 7.7, 1.2 Hz, 1H), 7.30 (d, J = 2.0 Hz,
1H), 7.52 (td, J = 7.2, 1.5 Hz, 1H), 7.56 (dd, J = 8.1, 1.0 Hz, 1H),
7.67 (dd, J = 7.9, 1.2 Hz, 1H), 8.16 (d, J = 9.1 Hz, 1H), 8.60−8.64
(m, 1H) (the amide proton difficult to be observed). 13C{1H} NMR
(150 MHz, DMSO-d6) δ 14.1, 20.0, 31.4, 39.1, 116.6, 119.2, 122.3,
124.4, 127.8, 128.8, 129.4, 131.8, 134.0, 138.3, 141.0, 141.6, 167.7.
MS (EI) m/z: (%) 349 (22), 347 (57, [M+]), 303 (45), 301 (88), 228
(100), 200 (58). HRMS (EI) m/z: Calcd for C17H1835ClN3O3 [M+]
347.1037; Found 347.1046.
N-(5-Methoxy-2-nitrophenyl)-N-{2-[(4-methylpiperazin-1-yl)-
carbonyl]phenyl}amine (3i). Yellow crystals, mp 98−101 °C
1
(EtOAc/hexane), 765 mg, 85% yield. H NMR (500 MHz, CDCl3)
δ 2.23−2.31 (m, 5H), 2.37 (br s, 2H), 3.35 (br s, 2H), 3.72 (br s,
2H), 3.77 (s, 3H), 6.37 (dd, J = 9.4, 2.7 Hz, 1H), 6.59 (d, J = 2.7 Hz,
1H), J = 7.27 (td, J = 7.4, 1.7 Hz, 1H), 7.39 (dd, J = 7.4, 0.9 Hz, 1H),
7.42−7.48 (m, 2H), 8.17 (d, J = 9.4 Hz, 1H), 9.90 (br s, 1H).
13C{1H} NMR (125 MHz, CDCl3) δ 41.7, 46.0, 47.1, 54.5, 55.0, 55.8,
98.1, 106.9, 124.5, 125.6, 128.1, 128.5, 128.9, 130.2, 131.5, 135.7,
144.4, 165.4, 167.7. MS (EI) m/z: (%) 370 (34, [M+]), 335 (17), 225
(77), 70 (100). HRMS (EI) m/z: Calcd for C19H22N4O4 [M+]
370.1641; Found 370.1642.
N-{4-Chloro-2-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-N-(5-
chloro-2-nitrophenyl)amine (3p). Yellow crystals, mp 149−151 °C
E
J. Org. Chem. XXXX, XXX, XXX−XXX