Medicinal Chemistry Research
2
2
(ArCH, JC-F = 22 Hz), 119.29 (ArC, JC(Cl)-F = 18 Hz),
6.84 Hz, Jm = 2.60 Hz, ArH, meta to fluoro), 8.50 (s, 1H,
-N = CH-N) and 9.51 ppm (s, 1H, -NH-). 13C NMR
(DMSO-d6): δ 23.98 (CH2, pyrrolidine), 26.17 (CH2, pyr-
rolidine), 45.58 (NCH2, pyrrolidine), 46.17 (NCH2, pyrro-
3
121.67 (ArCH, JC-F = 6 Hz), 123.41 (ArCH), 136.18
(ArC, JC-F = 3 Hz), 147.01 (ArC), 147.16 (ArC), 152.78
(ArC), 153.38 (ArC, JC-F = 243 Hz), 154.32 (N = CH-N),
4
1
156.16 (ArC) and 165.10 ppm (C=O). ESI-MS m/z: 460.40
[M + H]+, 462.41 [MH + 2]+, 482.41 [M + Na]+. Anal.
calcd for C22H23ClFN5O3: C, 57.46; H, 5.04; N, 15.23%.
Found: C, 57.74; H, 5.22; N, 15.41%.
lidine), 56.41 (OCH3), 67.83 (OCH2), 103.77 (ArCH),
2
107.91 (ArCH), 109.04 (ArC), 117.04 (ArCH, JC-F
=
2
3
22 Hz), 119.29 (ArC, JC(Cl)-F = 18 Hz), 122.93 (ArCH,
4
JC-F = 7 Hz), 124.04 (ArCH), 137.16 (ArC, JC-F = 3 Hz),
147.67 (ArC), 148.08 (ArC), 153.30 (N = CH-N), 153.76
4-(3-Chloro-4-fluorophenylamino)-7-methoxy-6-[2-{4-
(4-fluorophenyl)piperazin-1-yl}-2-oxo]-ethoxyquinazoline
(13): Yield (0.11 g, 53.40%), m.p. 198–200 °C. FT-IR νmax
(KBr): 3357.77 (N–H), 2932.45 (asymmetric aliphatic
C–H), 2832.48 (symmetric aliphatic C–H), 1645.08 (amide
C=O), 1580.29 (C=N), 1505.93, 1430.81, 1282.60,
1220.57 (asymmetric C–O–C), 1145.62 (C–F), 1062.01 (C-
1
(ArC, JC-F = 256 Hz), 154.89 (ArC), 156.56 (ArC) and
165.51 ppm (C=O). ESI-MS m/z: 429.40 [M-H]+, 431.10
[M + H]+, 453.20 [M + Na]+. Anal. calcd for
C21H20ClFN4O3: C, 58.54; H, 4.68; N, 13.00%. Found: C,
58.80; H, 4.32; N, 12.82%.
4-(3-Chloro-4-fluorophenylamino)-7-methoxy-6-[2-(4-
phenylpiperazin-1-yl)-2-oxo]ethoxy-quinazoline (15): Yield
(0.13 g, 65.32%), m.p. 225–227 °C. FT-IR νmax (KBr):
3348.45 (N–H), 2927.12 (asymmetric aliphatic C–H),
2818.80 (symmetric aliphatic C–H), 1644.60 (amide C=O),
1579.02 (C=N), 1502.24, 1428.01, 1282.39, 1222.22
(asymmetric C–O–C), 1141.85 (C–F), 1057.88 (C-Cl),
1
Cl), 1024.38 (symmetric C–O–C), 817.83 cm−1. H NMR
(DMSO-d6): δ 3.11 (br s, 2H, -NCH2-, piperazine), 3.20 (br
s, 2H, -NCH2-, piperazine), 3.74 (br s, 4H, -N(CH2)2-,
piperazine), 3.97 (s, 3H, -OCH3), 4.99 (s, 2H, -OCH2-),
6.93-7.02 (m, 4H, ArH, 4-fluorophenyl), 7.19 (s, 1H, ArH,
quinazoline), 7.25 (t, 1H, Jo = 8.96 Hz, ArH, ortho to
fluoro), 7.76–7.80 (m, 1H, ArH, ortho to chloro), 7.83 (s,
1H, ArH, quinazoline), 8.10 (dd, 1H, Jo = 6.78 Hz, Jm =
2.58 Hz, ArH, meta to fluoro), 8.50 (s, 1H, -N = CH-N) and
9.42 ppm (s, 1H, -NH-). 13C NMR (DMSO-d6): δ 41.36
(NCH2, piperazine), 44.60 (NCH2, piperazine), 49.35
(NCH2, piperazine), 49.70 (NCH2, piperazine), 55.86
(OCH3), 67.35 (OCH2), 103.75 (ArCH), 107.38 (ArCH),
1020.71 (symmetric C–O–C), 848.07 cm−1
.
1H NMR
(CDCl3): δ 3.00 (t, 2H, J = 5.04 Hz, -NCH2-, piperazine),
3.12 (t, 2H, J = 4.86 Hz, -NCH2-, piperazine), 3.67 (t, 2H, J
= 5.04 Hz, -NCH2-, piperazine), 3.72 (t, 2H, J = 4.90 Hz,
-NCH2-, piperazine), 3.81 (s, 3H, -OCH3), 4.91 (s, 2H,
-OCH2-), 6.79–6.86 (m, 3H, ArH, phenylpiperazine), 6.99
(t, 1H, Jo = 8.80 Hz, ortho to fluoro), 7.01 (s, 1H, ArH,
quinazoline), 7.19 (t, 2H, Jo = 7.48 Hz, ArH, phenylpiper-
azine), 7.46–7.50 (m, 1H, ArH, ortho to chloro), 7.55 (s,
1H, ArH, quinazoline), 7.67 (dd, 1H, Jo = 6.60 Hz, Jm =
2.60 Hz, ArH, meta to fluoro), 8.35 (s, 1H, -NH-, D2O
exchangeable) and 8.49 ppm (s, 1H, -N = CH-N). 13C NMR
(CDCl3): δ 45.49 (NCH2, piperazine), 49.22 (NCH2,
piperazine), 49.87 (NCH2, piperazine), 50.61 (NCH2,
2
108.69 (ArC), 115.26 (2 × ArCH, JC-F = 22 Hz), 116.27
2
3
(ArCH, JC-F = 21 Hz), 117.84 (2 × ArCH, JC-F = 7 Hz),
2
3
119.03 (ArC, JC(Cl)-F = 18 Hz), 121.87 (ArCH, JC-F
=
7 Hz), 123.24 (ArCH), 136.62 (ArC), 147.29 (ArC), 147.56
(ArC), 147.58 (ArC), 152.82 (N = CH-N), 153.25 (ArC,
1JC-F = 249 Hz), 155.27 (ArC), 156.09 (ArC), 157.63 (ArC)
and 165.13 ppm (C=O). ESI-MS m/z: 538.60 [M-H]+,
540.26 [M + H]+. Anal. calcd for C27H24ClF2N5O3: C,
60.06; H, 4.48; N, 12.97 %. Found: C, 59.74; H, 4.22; N,
13.19%.
piperazine), 56.06 (OCH3), 68.13 (OCH2), 103.92 (ArCH),
2
108.04 (ArCH), 108.93 (ArC), 116.23 (ArCH, JC-F
=
=
2
22 Hz), 116.74 (2 × ArCH), 120.46 (ArC, JC(Cl)-F
3
4-(3-Chloro-4-fluorophenylamino)-7-methoxy-6-[2-(pyr-
18 Hz), 120.92 (ArCH), 121.83 (ArCH, JC-F = 7 Hz),
4
rolidin-1-yl)-2-oxo]ethoxyquinazoline
(14)
(0.11 g,
123.94 (ArCH), 129.33 (2 × ArCH), 135.70 (ArC, JC-F =
50.23%), m.p. 238–239 °C. FT-IR νmax (KBr): 3340.15
(N–H), 2976.09 (asymmetric aliphatic C–H), 2887.27
(symmetric aliphatic C–H), 1637.95 (amide C=O), 1582.27
(C=N), 1504.66, 1432.38, 1286.74, 1224.26 (asymmetric
C–O–C), 1148.59 (C–F), 1083.69 (C-Cl), 1057.80 (sym-
metric C–O–C), 845.90 cm−1. 1H NMR (DMSO-d6): δ 1.80
(p, 2H, J = 6.71 Hz, -CH2-, pyrrolidine), 1.93 (p, 2H, J =
6.70 Hz, -CH2-, pyrrolidine), 3.37 (t, 2H, J = 6.80 Hz,
-NCH2- pyrrolidine), 3.55 (t, 2H, J = 6.70 Hz, -NCH2-
pyrrolidine), 3.95 (s, 3H, -OCH3), 4.88 (s, 2H, -OCH2-),
7.22 (s, 1H, ArH, quinazoline), 7.45 (t, 1H, Jo = 9.10 Hz,
ArH, ortho to fluoro), 7.73–7.76 (m, 1H, ArH, ortho to
chloro), 7.77 (s, 1H, ArH, quinazoline), 8.11 (dd, 1H, Jo =
3 Hz), 146.92 (ArC), 147.93 (ArC), 150.58 (ArC), 153.90
(N = CH-N), 154.46 (ArC, JC-F = 245 Hz), 154.63 (ArC),
156.56 (ArC) and 166.89 ppm (C=O). ESI-MS m/z: 520.50
[M-H]+, 522.10 [M + H]+. Anal. calcd for C27H25ClFN5O3:
C, 62.13; H, 4.83; N, 13.42%. Found: C, 62.41; H, 4.52; N,
13.76%.
1
4-(3-Chloro-4-fluorophenylamino)-7-methoxy-6-[2-{4-
(4-nitrophenyl)piperazin-1-yl}-2-oxo]
ethoxyquinazoline
(16): Yield (0.105 g, 41.82%), m.p. 240–242 °C. FT-IR νmax
(KBr): 3362.71 (N–H), 2922.86 (asymmetric aliphatic
C–H), 2848.27 (symmetric aliphatic C–H), 1638.52 (amide
C=O), 1595.22 (C=N), 1502.27, 1430.92, 1321.95,
1229.41 (asymmetric C–O–C), 1110.65 (C–F), 1069.40