H. Kakuta et al.
MED
(d, J=9.0 Hz, 1H), 4.21 (t, J=6.5 Hz, 2H), 1.79 (sex, J=7.0 Hz, 2H),
0.96 ppm (t, J=7.0 Hz, 3H).
N-(3-Chlorophenyl)-2-ethoxy-5-nitrobenzamide (13s): According
to general procedure GP-A, 13s was obtained as a white solid
(56%): 1H NMR (300 MHz, CDCl3): d=9.84 (s, 1H), 9.18 (d, J=
3.0 Hz, 1H), 8.37 (dd, J=9.0, 3.0 Hz, 1H), 7.78 (t, J=2.0 Hz, 1H),
7.48 (ddd, J=8.0, 2.0, 1.0 Hz, 1H), 7.30 (t, J=8.0 Hz, 1H), 7.14 (ddd,
J=8.0, 2.0, 1.0 Hz, 1H), 7.13 (d, J=9.0 Hz), 1H, 4.43 (q, J=7.0 Hz,
2H), 1.72 ppm (t, J=7.0 Hz, 3H).
2-Isopropoxy-5-nitro-N-(4-trifluoromethylphenyl)benzamide
(13j): According to general procedure GP-A, 13j was obtained as a
1
white solid (62%): H NMR (300 MHz, [D6]DMSO): d=10.58 (s, 1H),
8.43 (d, J=3.0 Hz, 1H), 8.37 (dd, J=9.0, 3.0 Hz, 1H), 7.92 (d, J=
8.5 Hz, 2H), 7.74 (d, J=8.5 Hz, 2H), 7.44 (d, J=9.0 Hz, 1H), 4.92
(sep, J=6.0 Hz, 1H), 1.37 ppm (d, J=6.0 Hz, 6H).
N-(2-Chlorophenyl)-2-ethoxy-5-nitrobenzamide (13t): According
to general procedure GP-A, 13t was obtained as a white solid
(53%): 1H NMR (300 MHz, CDCl3): d=10.12 (s, 1H), 9.21 (d, J=
3.0 Hz, 1H), 8.61 (dd, J=8.5, 1.5 Hz, 1H), 8.38 (dd, J=9.0, 3.0 Hz,
1H), 7.43 (dd, J=8.0, 1.5 Hz, 1H), 7.35 (td, J=8.0, 1.5 Hz, 1H), 7.16
(d, J=9.0 Hz, 1H), 7.11 (td, J=8.0, 1.5 Hz, 1H), 4.47 (q, J=7.0 Hz,
2H), 1.65 ppm (t, J=7.0 Hz, 3H).
2-Isopropoxy-5-nitro-N-(3-trifluoromethylphenyl)benzamide
(13k): According to general procedure GP-A, 13k was obtained as
a white solid (58%): 1H NMR (300 MHz, [D6]DMSO): d=10.55 (s,
1H), 8.43 (d, J=3.0 Hz, 1H), 8.36 (dd, J=9.0, 3.0 Hz, 1H), 8.22 (s,
1H), 7.86 (d, J=8.5 Hz, 1H), 7.61 (t, J=8.5 Hz, 1H), 7.46 (d, J=
8.5 Hz, 1H), 7.43 (d, J=9.0 Hz, 1H), 4.94 (sep, J=6.0 Hz, 1H),
1.37 ppm (d, J=6.0 Hz, 6H).
2-Ethoxy-N-(3-hydroxyphenyl)-5-nitrobenzamide (13u): Accord-
ing to general procedure GP-A, 13u was obtained as a pale yellow
solid (86%): 1H NMR (500 MHz, CDCl3): d=10.13(s, 1H), 9.46 (s,
1H), 8.42 (d, J=3.0 Hz, 1H), 8.36 (dd, J=9.0, 3.0 Hz, 1H), 7.38 (d,
J=9.0 Hz, 1H), 7.31 (t, J=2.0 Hz, 1H), 7.12 (t, J=8.0 Hz, 1H), 7.05
(td, J=8.0, 1,0 Hz, 1H), 6.52–6.50 (m, 1H), 4.30 (q, J=7.0 Hz, 2H),
1.42 ppm (t, J=7.0 Hz, 3H).
N-(4-Chlorophenyl)-2-ethoxy-5-nitrobenzamide (13l): According
to general procedure GP-A, 13l was obtained as a white solid
(91%): 1H NMR (300 MHz, CDCl3): d=10.39 (s, 1H), 8.42 (d, J=
3.0 Hz, 1H), 8.38 (dd, J=9.0, 3.0 Hz, 1H), 7.75 (d, J=8.5 Hz, 2H),
7.41 (d, J=8.5 Hz, 2H), 7.39 (d, J=9.0 Hz, 1H), 4.30 (q, J=7.0 Hz,
1H), 1.41 ppm (t, J=7.0 Hz, 3H).
2-Ethoxy-5-nitro-N-phenylbenzamide (13m): According to gener-
al procedure GP-A, 13m was obtained as a white solid (54%):
1H NMR (300 MHz, [D6]DMSO): d=10.25 (s, 1H), 8.44 (d, J=3.0 Hz,
1H), 8.37 (dd, J=9.0, 3.0 Hz, 1H), 7.71 (dd, J=7.5, 1.0 Hz, 2H), 7.39
(d, J=9.0 Hz, 1H), 7.37 (t, J=7.5 Hz, 2H), 7.12 (tt, J=7.5, 1.0 Hz,
1H), 4.31 (q, J=7.09 Hz, 2H), 1.43 ppm (t, J=7.0 Hz, 3H).
2-Ethoxy-N-(2-methoxyphenyl)-5-nitrobenzamide (13v): Accord-
ing to general procedure GP-A, 13v was obtained as a white solid
(16%): 1H NMR (500 MHz, CDCl3): d=10.19 (s, 1H), 9.21 (d, J=
3.0 Hz, 1H), 8.64 (d, J=9.0 Hz, 1H), 8.33 (dd, J=9.0, 3.0 Hz, 1H),
7.11 (t, J=7.5 Hz, 1H), 7.10 (d, J=7.5 Hz, 1H), 7.04 (t, J=7.5 Hz,
1H), 6.94 (d, J=7.5 Hz, 1H), 4.41 (q, J=7.0 Hz, 2H), 3.93 (s, 3H),
1.68 ppm (t, J=7.0 Hz, 3H).
2-Ethoxy-N-(4-methylphenyl)-5-nitrobenzamide (13n): According
to general procedure GP-A, 13n was obtained as a white solid
2-Ethoxy-N-(3-methoxyphenyl)-5-nitrobenzamide (14u): K2CO3
(1.09 mmol) and methyl iodide (2.16 mmol) were added to a solu-
tion of compound 13u (0.72 mmol) in DMF (10 mL). The reaction
mixture was stirred overnight at 608C, then acidified with 2n HCl
(100 mL) and extracted with EtOAc (50 mLꢂ3). The organic layer
was washed with H2O (50 mL) and brine (50 mL), dried over
MgSO4, and evaporated under reduced pressure. The residue was
purified by flash column chromatography to yield 14u as a yellow
1
(49%): H NMR (300 MHz, [D6]DMSO): d=10.18 (s, 1H), 8.43 (d, J=
3.0 Hz, 1H), 8.37 (dd, J=9.0, 3.0 Hz, 1H), 7.60 (d, J=8.5 Hz, 2H),
7.39 (d, J=9.0 Hz, 1H), 7.17 (d, J=8.5 Hz, 2H), 4.31 (q, J=7.0 Hz,
2H), 2.29 (s, 3H), 1.42 ppm (t, J=7.0 Hz, 3H).
2-Ethoxy-N-(4-ethylphenyl)-5-nitrobenzamide (13o): According
to general procedure GP-A, 13o was obtained as a white solid
1
(76%): H NMR (300 MHz, [D6]DMSO): d=10.18 (s, 1H), 8.44 (d, J=
1
2.5 Hz, 1H), 8.37 (dd, J=9.0, 2.5 Hz, 1H), 7.62 (d, J=8.5 Hz, 2H),
7.39 (d, J=9.0 Hz, 1H), 7.20 (d, J=8.5 Hz, 2H), 4.31 (q, J=7.0 Hz,
2H), 3.32 (q, J=8.0 Hz, 2H), 1.42 (t, J=7.0 Hz, 3H), 1.18 ppm (t, J=
8.0 Hz, 3H).
solid (85%): H NMR (500 MHz, CDCl3): d=9.81 (s, 1H), 9.19 (d, J=
3.0 Hz, 1H), 8.35 (d, J=9.0, 3.0 Hz, 1H), 7.51 (s, 1H), 7.26 (t, J=
8.0 Hz, 1H), 7.26 (t, J=8.0 Hz, 1H), 7.12 (t, J=9.0 Hz, 1H), 7.05 (d,
J=8.0 Hz, 1H), 6.72 (dd, J=8.0, 2.5 Hz, 1H), 4.41 (q, J=7.0 Hz, 2H),
3.85 (s, 3H), 1.71 ppm (t, J=7.0 Hz, 3H).
2-Ethoxy-5-nitro-N-(4-isopropylphenyl)benzamide (13p): Accord-
ing to general procedure GP-A, 13p was obtained as a white solid
4-Amino-2-methoxy-N-(4-trifluoromethylphenyl)benzamide (9c):
According to general procedure GP-C, 9c was obtained yield as
pale yellow needles after recrystallization from EtOAc/n-hexane
(90%): mp: 172.4–173.08C; 1H NMR (300 MHz, [D6]DMSO): d=
10.03 (s, 1H), 7.94 (d, J=8.5 Hz, 2H), 7.66 (d, J=8.5 Hz, 2H), 7.63
(d, J=8.5 Hz, 1H), 6.29 (d, J=2.0 Hz, 1H), 6.25 (dd, J=8.5, 2.0 Hz,
1H), 5.94 (brs, 2H), 3.92 ppm (s, 3H); IR (KBr): n=3506, 3364, 3231
(NH, NH2), 1673 cmÀ1 (CO); FAB m/z [M+H]+: 311; Anal. calcd for
C15H13F3N2O2: C 58.07, H 4.22 O 9.03, found: C 57.78, H 4.30, O
9.06.
1
(96%): H NMR (300 MHz, [D6]DMSO): d=10.19 (s, 1H), 8.43 (d, J=
3.0 Hz, 1H), 8.37 (dd, J=9.0, 3.0 Hz, 1H), 7.62 (d, J=8.5 Hz, 2H),
7.39 (d, J=9.0 Hz, 1H), 7.24 (d, J=8.5 Hz, 2H), 4.31 (q, J=7.0 Hz,
2H), 2.87 (sep, J=7.0 Hz, 1H), 1.42 (t, J=7.0 Hz, 3H), 1.20 ppm (d,
J=7.0 Hz, 6H).
2-Ethoxy-N-(4-hydroxyphenyl)-5-nitrobenzamide (13q): Accord-
ing to general procedure GP-A, 13q was obtained as a pale yellow
1
solid (27%): H NMR (300 MHz, [D6]DMSO): d=10.02 (s, 1H), 9.30
(s, 1H),8.43 (d, J=3.0 Hz, 1H), 8.36 (dd, J=9.0, 3.0 Hz, 1H), 7.50 (d,
J=8.5 Hz, 2H), 7.38 (d, J=9.5 Hz, 1H), 6.75 (d, J=9.5 Hz, 1H), 4.30
(q, J=7.0 Hz, 2H), 1.57 ppm (t, J=7.0 Hz, 3H).
5-Amino-2-methoxy-N-(4-trifluoromethylphenyl)benzamide (9d):
According to general procedure GP-B-1, 9d was obtained as color-
less needles after recrystallization from EtOAc/n-hexane (39%): mp:
146.0–148.08C; 1H NMR (300 MHz, [D6]DMSO): d=10.41 (s, 1H),
7.94 (d, J=8.5 Hz, 2H), 7.69 (d, J=8.5 Hz, 2H), 6.94 (d, J=3.0 Hz,
1H), 6.92 (d, J=9.0 Hz, 1H), 6.73 (dd, J=9.0, 3.0 Hz, 1H), 4.91 (brs,
2H), 3.79 ppm (s, 3H); IR (KBr): n=3428, 3338, 3243 (NH, NH2),
1668 cmÀ1 (CO); FAB m/z [M+H]+: 311; Anal. calcd for
2-Ethoxy-N-(4-methoxyphenyl)-5-nitrobenzamide (13r): Accord-
ing to general procedure GP-A, 13r was obtained as a yellow solid
1
(15%): H NMR (300 MHz, [D6]DMSO): d=10.13 (s, 1H), 8.44 (d, J=
3.0 Hz, 1H), 8.37 (dd, J=9.0, 3.0 Hz, 1H), 7.63 (d, J=9.0 Hz, 2H),
7.39 (d, J=9.0 Hz, 1H), 6.94 (d, J=9.0 Hz, 2H), 4.31 (q, J=7.0 Hz,
2H), 3.75 (s, 3H), 1.42 ppm (t, J=7.0 Hz, 3H).
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ChemMedChem 2011, 6, 550 – 560