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a solution of NaHCO3. The formed solid was then filtered, and puri-
fied by column chromatography with EtOAc as eluent.
for C21H13BrN6O5: C 49.53, H 2.57, N 16.50, found: C 49.61, H 2.52, O
16.73.
4-Amino-N-(4-((3-bromophenyl)amino)quinazolin-6-yl)benza-
mide (11a): Compound 11 a was synthesized from its nitro deriva-
tive 11 d by the same procedure as used for compound 3. Yield
30% (84 mg, yellow solid); mp: 288–2898C; 1H NMR (500 MHz,
[D6]DMSO): d=5.81 (s, 2H), 6.64 (d, J=8.7 Hz, 2H), 7.28 (ddd, J=
8.0, 1.7, 0.9 Hz, 1H), 7.34 (t, J=8.0 Hz, 1H), 7.80 (t, J=8.5 Hz, 3H),
7.87–7.92 (m, 1H), 8.02 (dd, J=9.0, 2.2 Hz, 1H), 8.21 (t, J=1.9 Hz,
1H), 8.59 (s, 1H), 8.86 (d, J=2.0 Hz, 1H), 9.87 (s, 1H), 10.12 ppm (s,
1H); 13C NMR (126 MHz, [D6]DMSO): d=112.63, 112.96, 115.36,
120.45, 120.66, 121.11, 124.12, 125.71, 128.04, 128.36, 129.42,
130.28, 137.55, 141.26, 146.49, 152.40, 152.86, 157.21, 165.31 ppm;
MS (+ESI): m/z=433.99 [M+H]+; Anal. calcd for C21H16BrN5O: C
58.08, H 3.71, N 16.13, found: C 58.21, H 3.79, O 16.26.
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)-4-methoxybenza-
mide (11 f): Yield 62% (180 mg, yellow solid); purity 95.12%; mp:
331–3338C; H NMR (500 MHz, [D]TFA): d=4.15 (s, 3H), 7.31 (d, J=
1
8.9 Hz, 2H), 7.58 (t, J=8.1 Hz, 1H), 7.70 (d, J=9.0 Hz, 1H), 7.81 (d,
J=8.1 Hz, 1H), 7.95 (s, 1H), 8.15 (d, J=8.9 Hz, 2H), 8.23 (d, J=
9.0 Hz, 1H), 8.33 (dd, J=9.1, 1.7 Hz, 1H), 9.11 (s, 1H), 9.81 ppm (d,
J=1.4 Hz, 1H); 13C NMR (126 MHz, [D]TFA): d=57.61, 116.27,
116.59, 117.24, 123.63, 125.85, 126.43, 126.92, 131.06, 132.36,
133.57, 134.05, 135.38, 136.73, 137.23, 142.34, 151.54, 162.02,
166.22, 172.54 ppm; MS (+ESI): m/z=449.08 [M+H]+; Anal. calcd
for C22H17BrN4O2: C 58.81, H 3.81, N 12.47, found: C 58.89, H 3.88, O
12.55.
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)-3,4-dimethoxyben-
zamide (11g): Yield 46% (143, yellow solid); purity 95.54%; mp:
257–2588C; 1H NMR (500 MHz, [D]TFA): d=4.22 (s, 3H), 4.23 (s,
3H), 7.33 (d, J=8.6 Hz, 1H), 7.62 (t, J=8.1 Hz, 1H), 7.74 (ddd, J=
8.0, 2.0, 0.8 Hz, 1H), 7.80 (d, J=2.1 Hz, 1H), 7.85 (ddd, J=8.1, 1.8,
0.9 Hz, 1H), 7.91 (dd, J=8.5, 2.1 Hz, 1H), 8.00 (t, J=1.9 Hz, 1H),
8.20 (d, J=9.0 Hz, 1H), 8.31 (dd, J=9.0, 2.1 Hz, 1H), 9.08 (s, 1H),
9.83 ppm (d, J=2.0 Hz, 1H); 13C NMR (126 MHz, [D]TFA): d=55.76,
56.02, 111.73, 114.29, 114.60, 116.52, 121.46, 122.88, 123.79, 124.41,
125.16, 129.06, 131.52, 131.86, 133.26, 134.96, 135.50, 140.12,
149.24, 149.84, 154.06, 160.60, 170.37 ppm; MS (+ESI): m/z=
479.09 [M+H]+; Anal. calcd for C23H19BrN4O3: C 57.63, H 4.00, N
11.69, found: C 57.76, H 4.03, O 11.85.
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)-4-cyanobenzamide
(11b): Yield 27% (77 mg, white solid); mp: 347–3498C; 1H NMR
(500 MHz, [D6]DMSO): d=7.46 (t, J=8.0 Hz, 1H), 7.52 (ddd, J=8.0,
1.9, 1.0 Hz, 1H), 7.75 (ddd, J=8.0, 1.9, 1.0 Hz, 1H), 8.02 (t, J=
1.9 Hz, 1H), 8.05–8.09 (m, 3H), 8.24–8.27 (m, 2H), 8.29 (dd, J=9.1,
2.1 Hz, 1H), 8.94 (s, 1H), 9.24 (d, J=2.0 Hz, 1H), 11.25 (s, 1H),
11.61 ppm (s, 1H); 13C NMR (126 MHz, [D6]DMSO): d=114.01,
114.35, 114.64, 118.20, 120.89, 121.13, 123.62, 127.22, 128.71,
129.05, 130.62, 130.76, 132.60, 136.12, 137.89, 138.52, 138.60,
149.96, 159.62, 164.41 ppm; MS (+ESI): m/z=444.08 [M+H]+;
Anal. calcd for C22H14BrN5O: C 59.47, H 3.18, N 15.76, found: C
59.61, H 3.14, O 15.82.
4-Acetamido-N-(4-((3-bromophenyl)amino)quinazolin-6-yl)benza-
mide (11c): Yield 25% (76 mg, pale-yellow solid); mp: 338–3408C;
1H NMR (500 MHz, [D6]DMSO): d=2.10 (s, 3H), 7.29 (d, J=8.6 Hz,
1H), 7.35 (t, J=8.0 Hz, 1H), 7.76 (d, J=8.7 Hz, 2H), 7.83 (d, J=
8.9 Hz, 1H), 7.90 (d, J=8.1 Hz, 1H), 7.99–8.07 (m, 3H), 8.21 (s, 1H),
8.61 (s, 1H), 8.90 (d, J=1.8 Hz, 1H), 9.93 (s, 1H), 10.24 (s, 1H),
10.49 ppm (s, 1H); 13C NMR (126 MHz, [D6]DMSO): d=24.12, 113.52,
115.33, 117.54, 118.21, 120.71, 121.12, 124.17, 125.78, 128.21,
128.42, 128.64, 130.29, 136.98, 141.20, 142.52, 146.80, 153.14,
157.28, 164.96, 168.79 ppm; MS (+ESI): m/z=476.1 [M+H]+; Anal.
calcd for C23H18BrN5O2: C 58.00, H 3.81, N 14.70, found: C 58.13, H
3.79, O 14.84.
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)morpholine-4-car-
boxamide (11h): Yield 24% (65 mg, pale-brown solid); purity
95.33%; mp: 281–2838C; 1H NMR (500 MHz, [D6]DMSO): d=3.46–
3.54 (m, 4H), 3.61–3.69 (m, 4H), 7.27 (ddd, J=7.9, 1.8, 0.9 Hz, 1H),
7.33 (t, J=8.0 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 7.84 (dd, J=9.0,
2.2 Hz, 1H), 7.88 (d, J=7.9 Hz, 1H), 8.19 (s, 1H), 8.50 (d, J=2.0 Hz,
1H), 8.56 (s, 1H), 8.91 (s, 1H), 9.81 ppm (s, 1H); 13C NMR (126 MHz,
[D6]DMSO): d=44.14, 66.01, 112.12, 115.37, 120.60, 121.11, 124.05,
125.67, 127.78, 128.16, 130.27, 138.45, 141.27, 145.71, 152.43,
155.09, 157.05 ppm; MS (+ESI): m/z=428.05 [M+H]+; Anal. calcd
for C19H18BrN5O2: C 53.28, H 4.24, N 16.35, found: C 53.37, H 4.22, O
16.52.
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)-4-nitrobenzamide
(11d): Yield 62% (188 mg, orange solid); purity 95.77%; mp: 310–
3128C; 1H NMR (500 MHz, [D6]DMSO): d=7.36–7.47 (m, 2H), 7.79
(dt, J=7.0, 2.0 Hz, 1H), 7.96 (d, J=9.0 Hz, 1H), 8.08 (d, J=1.8 Hz,
1H), 8.19 (dd, J=9.0, 2.1 Hz, 1H), 8.27–8.34 (m, 2H), 8.36–8.45 (m,
2H), 8.81 (s, 1H), 9.10 (d, J=2.0 Hz, 1H), 10.94 (s, 1H), 11.18 ppm
(s, 1H); 13C NMR (126 MHz, [D6]DMSO): d=114.39, 114.51, 121.14,
122.55, 123.67, 126.10, 127.87, 129.35, 129.84, 130.51, 137.64,
139.57, 139.69, 146.99, 149.41, 151.30, 158.70, 160.05, 164.10 ppm;
MS (+ESI): m/z=464.08 [M+H]+; Anal. calcd for C21H14BrN5O3: C
54.33, H 3.04, N 15.08, found: C 54.36, H 3.10, O 15.21.
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)furan-2-carboxa-
mide (11i): Yield 43% (115 mg, white solid); mp: 334–3368C;
1H NMR (500 MHz, [D6]DMSO): d=6.76 (dd, J=3.5, 1.7 Hz, 1H), 7.46
(t, J=8.0 Hz, 1H), 7.52 (ddd, J=8.0, 1.9, 1.0 Hz, 1H), 7.59 (dd, J=
3.5, 0.7 Hz, 1H), 7.74 (ddd, J=8.0, 1.9, 1.0 Hz, 1H), 7.99–8.03 (m,
2H), 8.05 (d, J=9.0 Hz, 1H), 8.31 (dd, J=9.1, 2.1 Hz, 1H), 8.93 (s,
1H), 9.18 (d, J=2.0 Hz, 1H), 10.93 (s, 1H), 11.61 ppm (s, 1H);
13C NMR (126 MHz, [D6]DMSO): d=112.32, 113.99, 114.37, 115.78,
120.62, 121.13, 123.64, 127.24, 129.08, 130.63, 130.66, 135.62,
138.43, 138.57, 146.42, 146.85, 149.71, 156.43, 159.62 ppm; MS (+
ESI): m/z=408.99 [M+H]+; Anal. calcd for C19H13BrN4O2: C 55.76, H
3.20, N 13.69, found: C 55.80, H 3.24, O 13.78.
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)-3,5-dinitrobenza-
mide (11e): Yield 51% (167 mg, yellow solid); mp: 351–3528C;
1H NMR (500 MHz, [D6]DMSO): d=7.43 (t, J=8.0 Hz, 1H), 7.48 (ddd,
J=8.0, 1.8, 1.1 Hz, 1H), 7.78 (ddd, J=7.9, 1.9, 1.1 Hz, 1H), 8.02–8.10
(m, 2H), 8.33 (dd, J=9.0, 2.1 Hz, 1H), 8.91 (s, 1H), 9.02 (t, J=2.1 Hz,
1H), 9.18 (d, J=2.0 Hz, 1H), 9.27 (d, J=2.1 Hz, 2H), 11.54 (s, 1H),
11.68 ppm (s, 1H); 13C NMR (126 MHz, [D6]DMSO): d=114.12,
115.15, 121.11, 121.43, 121.62, 123.33, 126.87, 128.19, 128.70,
130.52, 136.59, 137.81, 138.83, 139.55, 148.13, 149.55, 150.41,
159.34, 161.72 ppm; MS (+ESI): m/z=509.05 [M+H]+; Anal. calcd
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)nicotinamide (11j):
Yield 50% (135 mg, pale-brown solid); purity 96.52%; mp: 280–
2818C; 1H NMR (500 MHz, [D6]DMSO): d=7.29 (ddd, J=8.0, 1.8,
1.0 Hz, 1H), 7.35 (t, J=8.0 Hz, 1H), 7.62 (ddd, J=8.0, 4.8, 0.8 Hz,
1H), 7.85 (d, J=8.9 Hz, 1H), 7.90 (ddd, J=8.2, 1.9, 1.0 Hz, 1H), 8.02
(dd, J=9.0, 2.2 Hz, 1H), 8.20 (t, J=1.9 Hz, 1H), 8.34–8.42 (m, 1H),
8.62 (s, 1H), 8.81 (dd, J=4.8, 1.6 Hz, 1H), 8.92 (d, J=2.1 Hz, 1H),
9.21 (dd, J=2.3, 0.7 Hz, 1H), 9.95 (s, 1H), 10.80 ppm (s, 1H);
13C NMR (126 MHz, [D6]DMSO): d=113.75, 115.31, 120.80, 121.12,
123.62, 124.26, 125.88, 128.33, 128.42, 130.07, 130.30, 135.44,
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ChemMedChem 0000, 00, 1 – 11
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