CHEMMEDCHEM
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N-(4-Nitrophenyl)quinolin-4-amine (26): Compound 26 was syn-
thesized according to the procedure described for 6, using 4-nitro-
aniline (4.13 g, 29.90 mmol) and 4-chloroquinoline (4.89 g,
29.90 mmol). The reaction mixture was filtered, and the resulting
solid was rinsed with Et2O and dried in vacuo to afford compound
HRMS (ESI): m/z [M+H]+ calcd for C27H24N7O: 462.2037, found:
462.2034.
N-[4-(Quinolin-4-ylamino)phenyl]-4-(pyridin-4-ylamino)benza-
mide (31): Compound 31 was synthesized according to the proce-
dure described for 10, using amine 29 (55 mg, 0.16 mmol) and 4-
chloropyridine hydrochloride (47 mg, 0.31 mmol). Purification by
preparative HPLC (H2O/CH3CN, 90:10!0:100) gave compound 31
26 as
a
pale brown solid (3.73 g, 47%): 1H NMR (500 MHz,
[D6]DMSO): d=7.26 (d, J=6.8 Hz, 1H), 7.80 (d, J=8.9 Hz, 2H), 7.87
(td, J=7.1, 1.3 Hz, 1H), 8.08 (td, J=7.1, 1.3 Hz, 1H), 8.15 (d, J=
8.5 Hz, 1H), 8.40 (d, J=9.1 Hz, 2H), 8.70 (d, J=6.8 Hz, 1H), 8.84 (d,
J=8.2 Hz, 1H), 11.23 (s, 1H), 15.03 ppm (s, 1H); 13C NMR (126 MHz,
[D6]DMSO): d=102.2, 118.6, 121.0, 124.4, 125.8, 128.0, 134.6, 139.0,
144.0, 144.6, 145.2, 154.3 ppm; HRMS (ESI): m/z [M+H]+ calcd for
C24H24N7O: 266.0924, found: 266.0928.
1
as a yellow solid (25 mg, 38%): H NMR (500 MHz, [D6]DMSO): d=
6.84 (d, J=5.5 Hz, 1H), 7.05 (d, J=6.4 Hz, 2H), 7.31 (d, J=8.8 Hz,
2H), 7.35 (d, J=7.0 Hz, 2H), 7.52 (td, J=7.0, 1.2 Hz, 1H), 7.69 (td,
J=6.9, 1.2 Hz, 1H), 7.84 (d, J=8.9 Hz, 2H), 7.86 (d, J=8.4 Hz, 1H),
7.97 (d, J=8.7 Hz, 2H), 8.28 (d, J=6.3 Hz, 2H), 8.39 (d, J=8.5 Hz,
1H), 8.43 (d, J=5.4 Hz, 1H), 8.93 (s, 1H), 9.18 (s, 1H), 10.17 ppm (s,
1H); 13C NMR (126 MHz, [D6]DMSO): d=100.8, 110.2, 117.6, 119.4,
121.2, 121.9, 123.3, 124.4, 127.6, 129.0, 129.1, 129.1, 135.5, 135.6,
143.8, 148.1, 148.8, 148.8, 150.2, 157.6, 164.6 ppm; HRMS (ESI): m/z
[M+H]+ calcd for C27H22N5O: 432.1824, found: 432.1815.
N-(Quinolin-4-yl)benzene-1,4-diamine (27): Compound 27 was
synthesized according to the procedure described for 7, using 26
(3.73 g, 14.07 mmol). The filtrate was concentrated in vacuo and
purified by flash chromatography (CH2Cl2/MeOH, 100:0!70:30) to
1
give amine 27 as a brown solid (2.93 g, 89%): H NMR (500 MHz,
N-[4-(Quinolin-4-ylamino)phenyl]-4-(2,6-diaminopyrimidin-4-yl-
amino)benzamide (32): Compound 32 was synthesized according
to the procedure described for 10, using amine 29 (80 mg,
[D6]DMSO): d=5.33 (br s, 2H), 6.56 (d, J=6.7 Hz, 1H), 6.69 (d, J=
8.6 Hz, 2H), 7.06 (d, J=8.6 Hz, 2H), 7.63–7.70 (m, 1H), 7.86–7.91
(m, 1H), 7.94 (d, J=8.3 Hz, 1H), 8.39 (d, J=6.6 Hz, 1H), 8.59 (d, J=
8.5 Hz, 1H), 10.11 ppm (br s, 1H); 13C NMR (126 MHz, [D6]DMSO):
d=99.5, 114.5, 117.4, 122.6, 122.9, 125.5, 126.1, 126.7, 132.5, 141.2,
144.6, 148.1, 154.1 ppm; MS (ESI): m/z=236 [M+H]+.
0.24 mmol)
and
2,6-diamino-4-chloropyrimidine
(32 mg,
0.24 mmol). Purification by preparative HPLC (H2O/CH3CN, 90:10!
1
0:100) gave compound 32 as a white solid (39 mg, 38%): H NMR
(500 MHz, [D6]DMSO): d=5.26 (s, 1H), 5.76 (br s, 2H), 5.92 (br s,
2H), 6.82 (d, J=5.3 Hz, 1H), 6.84 (d, J=5.3 Hz, 1H), 7.22 (d, J=
5.1 Hz, 1H), 7.34 (d, J=8.8 Hz, 1H), 7.52 (td, J=6.9, 1.4 Hz, 1H),
7.69 (td, J=6.9, 1.3 Hz, 1H), 7.79 (d, J=8.9 Hz, 1H), 7.88–7.82 (m,
5H), 8.39 (br d, J=8.6 Hz, 1H), 8.43 (d, J=5.3 Hz, 1H), 8.92 (br s,
2H), 10.06 ppm (br s, 1H); 13C NMR (126 MHz, [D6]DMSO): d=77.5,
100.9, 117.4, 117.7, 119.5, 121.3, 122.0, 123.5, 124.5, 125.6, 128.4,
129.2, 135.5, 135.9, 145.2, 148.2, 148.9, 150.7, 161.0, 162.9, 164.8,
165.0 ppm; HRMS (ESI): m/z [M+H]+ calcd for C26H23N8O1:
463.1989, found: 463.1987.
N-[4-(Quinolin-4-ylamino)phenyl]-4-nitrobenzamide (28). Com-
pound 28 was synthesized according to the procedure described
for 8, using 4-nitrobenzoyl chloride (1.37 g, 7.40 mmol) and amine
27 (1.74 g, 7.40 mmol). The filtrate was concentrated in vacuo and
purified by flash chromatography (CH2Cl2/MeOH, 100:0!70:30) to
give compound 28 as a yellow solid (2.60 g, 93%): 1H NMR
(500 MHz, [D6]DMSO): d=6.84 (d, J=6.3 Hz, 1H), 7.47 (d, J=8.7 Hz,
2H), 7.69–7.75 (m, 2H), 7.88–7.91 (m, 1H), 7.93–7.98 (m, 3H), 8.23
(d, J=8.8 Hz, 2H), 8.40 (d, J=8.8 Hz, 2H), 8.50 (d, J=6.3 Hz, 1H),
8.60 (d, J=8.5 Hz, 1H), 8.60 (d, J=8.5 Hz, 1H), 10.76 ppm (s, 1H);
MS (ESI): m/z=385 [M+H]+.
N-[4-(Quinolin-4-ylamino)phenyl]-4-(2-phenylquinolin-4-yl-
amino)benzamide (33): Compound 33 was synthesized according
to the procedure described for 10, using amine 29 (80 mg,
0.24 mmol) and 4-chloro-2-phenylquinoline (81 mg, 0.34 mmol).
Purification by preparative HPLC (H2O/CH3CN, 90:10!0:100) gave
N-[4-(Quinolin-4-ylamino)phenyl]-4-aminobenzamide (29): Com-
pound 29 was synthesized according to the procedure described
for 7, using 28 (1.40 g, 3.64 mmol). The filtrate was concentrated in
vacuo and purified by flash chromatography (CH2Cl2/MeOH,
100:0!80:20) to give amine 29 as a yellow solid (326 mg, 25%):
1H NMR (500 MHz, [D6]DMSO): d=5.77 (s, 1H), 6.61 (d, J=8.7 Hz,
2H), 6.78 (d, J=6.1 Hz, 1H), 7.36 (d, J=8.8 Hz, 2H), 7.65 (t, J=
8.9 Hz, 1H), 7.73 (d, J=8.7 Hz, 2H), 7.84–7.81 (m, 1H), 7.88 (d, J=
8.8 Hz, 1H), 7.91 (br d, J=8.3 Hz, 1H), 8.46 (d, J=6.1 Hz, 1H), 8.63
(br d, J=7.9 Hz, 1H), 9.89 ppm (br s, 1H); MS (ESI): m/z=355
[M+H]+.
1
compound 33 as a white solid (116 mg, 92%): H NMR (500 MHz,
[D6]DMSO): d=6.85 (d, J=5.2 Hz, 1H), 7.36 (d, J=8.8 Hz, 2H),
7.54–7.46 (m, 4H), 7.62–7.56 (m, 3H), 7.69 (td, J=6.9, 1.3 Hz, 1H),
7.37 (s, 1H), 7.77 (td, J=6.9, 1.3 Hz, 1H), 7.85–7.88 (m, 3H), 8.01
(dd, J=8.5, 0.9 Hz, 1H), 8.06 (d, J=8.7 Hz, 2H), 8.09–8.11 (m, 2H),
8.40 (br d, J=8.5 Hz, 2H), 8.44 (d, J=5.2 Hz, 1H), 8.94 (br s, 1H),
9.34 (br s, 1H), 10.15 ppm (br s, 1H); 13C NMR (126 MHz,
[D6]DMSO): d=101.4, 120.0, 120.1, 121.7, 122.5, 122.7, 123.9, 124.9,
125.5, 125.6, 127.5, 128.9, 129.2, 129.6, 129.7, 129.8, 130.0, 136.1,
136.2, 139.6, 139.9, 144.9, 147.7, 148.6, 149.3, 149.5, 151.1, 157.1,
165.2 ppm; HRMS (ESI): m/z [M+H]+ calcd for C37H28N5O:
558.2288, found: 558.2292.
N-[4-(Quinolin-4-ylamino)phenyl]-4-(2-amino-6-methylpyrimidin-
4-ylamino)benzamide (30): Compound 30 was synthesized ac-
cording to the procedure described for 10, using amine 29 (70 mg,
0.20 mmol) and 2-amino-4-chloro-6-methylpyrimidine (43 mg,
0.30 mmol). Purification by preparative HPLC (H2O/CH3CN, 90:10!
N-(4-Nitrophenyl)-4-nitrobenzamide (34): Compound 34 was syn-
thesized according to the procedure described for 8, using 4-nitro-
benzoyl chloride (6.72 mg, 3.62 mmol) and 4-nitroaniline (5.0 g,
3.62 mmol). Filtration of the precipitate and drying in vacuo gave
1
0:100) gave compound 30 as a white solid (58 mg, 64%): H NMR
(500 MHz, [D6]DMSO): d=5.95 (s, 1H), 6.27 (br s, 2H), 6.83 (d, J=
5.3 Hz, 1H), 7.34 (d, J=8.8 Hz, 1H), 7.52 (td, J=6.9, 1.2 Hz, 1H),
7.69 (td, J=6.8, 1.3 Hz, 1H), 7.83 (d, J=8.9 Hz, 2H), 7.86 (dd, J=
8.6, 1.0 Hz, 1H), 7.94–7.88 (m, 4H), 8.39 (br d, J=8.0 Hz, 1H), 8.43
(d, J=5.3 Hz, 1H), 8.92 (br s, 1H), 9.34 (br s, 1H), 10.12 ppm (br s,
1H); 13C NMR (126 MHz, [D6]DMSO): d=23.6, 95.5, 100.9, 117.9,
119.5, 121.3, 122.0, 123.5, 124.5, 126.7, 128.5, 129.2, 129.2, 135.6,
135.8, 144.2, 148.2, 148.9, 150.7, 161.1, 162.9, 164.9, 165.6 ppm;
compound 34 as
a
yellow solid (10.29 mg, 99%): 1H NMR
(500 MHz, [D6]DMSO): d=8.09 (d, J=8.3 Hz, 2H), 8.24 (d, J=8.9 Hz,
2H), 8.29 (d, J=9.2 Hz, 2H), 8.39 (d, J=8.8 Hz, 2H), 11.20 ppm (br
s, 1H); 13C NMR (126 MHz, [D6]DMSO): d=120.1, 123.6, 124.8, 129.6,
139.8, 142.8, 145.0, 149.4, 164.7 ppm.
N-(4-Aminophenyl)-4-aminobenzamide (35): Compound 35 was
synthesized according to the procedure described for 7, using
ꢁ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemMedChem 2014, 9, 590 – 601 599