D. Kumar et al. / European Journal of Medicinal Chemistry 89 (2015) 490e502
499
8.33 (brs, 1H), 9.16 (s, 1H); 13C NMR (100 MHz, DMSO-d6):
d
42.77,
C
22H20BrClN6: 482.0621, found: 483.1493 (MþH)þ, 485.1466
54.97, 93.97, 97.55, 98.70, 117.40, 123.82, 124.10, 127.54, 133.40,
142.14, 149.02, 150.10, 151.96, 160.48, 160.70, 162.0; ESI-HRMS (m/z)
calculated for C23H23ClN6O2: 450.1571, found: 451.1548 (MþH)þ,
453.1848 (M þ 2)þ; Anal. calcd. for C23H23ClN6O2: C, 61.26; H, 5.14;
Cl, 7.86; N, 18.64; O, 7.10, found: C, 61.32; H, 5.23; Cl, 7.80; N, 18.59;
O, 7.15.
(M þ 2)þ; Anal. calcd. for C22H20BrClN6: C, 54.62; H, 4.17; Br, 16.52;
Cl, 7.33; N, 17.37, found: C, 54.67; H, 4.29; Br, 16.47; Cl, 7.20; N, 17.31.
4.4.12. N2-(3-(7-Chloroquinolin-4-ylamino)propyl)-N4-p-
tolylpyrimidine-2,4-diamine (8e)
Yield 70%; mp 193e195 ꢀC; IR (KBr, cmꢂ1): 3432, 3245, 2924,
2861, 1578, 1527, 1510, 1425, 1334, 1238, 1136, 1084, 976, 907, 877,
4.4.8. N2-(3-(7-Chloroquinolin-4-ylamino)propyl)-N4-
phenylpyrimidine-2,4-diamine (8a)
795; 1H NMR (400 MHz, DMSO-d6):
d 1.89e1.93 (m, 2H), 2.18 (s, 3H,
CH3), 3.31e3.34 (m, 4H), 5.94 (d, J ¼ 5.8 Hz, 1H), 6.45 (d, J ¼ 5.1 Hz,
1H), 6.81 (brs, 1H), 7.10 (brs, 2H), 7.34 (t, J ¼ 5.1 Hz, 1H), 7.42 (dd,
J ¼ 2.2, 8.7 Hz, 1H), 7.57 (d, J ¼ 8.0 Hz, 2H), 7.76 (d, J ¼ 2.2 Hz, 1H),
7.80 (d, J ¼ 5.8 Hz, 1H), 8.24 (d, J ¼ 8.7 Hz, 1H), 8.34 (d, J ¼ 5.8 Hz,
Yield 70%; mp 190e193 ꢀC; IR (KBr, cmꢂ1): 3436, 3232, 3038,
2924, 2885, 1580, 1525, 1495, 1436, 1379, 1356, 1332, 1256, 1131,
1079, 975, 904, 879, 853, 792; 1H NMR (400 MHz, DMSO-d6):
d
1.90e1.93 (m, 2H), 3.31e3.33 (m, 2H), 3.38e3.40 (m, 2H), 5.98 (d,
1H), 9.02 (s, 1H); 13C NMR (100 MHz, DMSO-d6):
d 21.24, 28.78,
J ¼ 5.8 Hz, 1H), 6.45 (d, J ¼ 5.1 Hz, 1H), 6.85 (brs, 1H), 6.90 (t,
J ¼ 7.3 Hz, 1H), 7.23 (t, J ¼ 8.0 Hz, 2H), 7.34 (t, J ¼ 5.1 Hz, 1H), 7.42
(dd, J ¼ 2.2, 9.5 Hz, 1H), 7.72 (d, J ¼ 8.0 Hz, 2H), 7.76 (d, J ¼ 2.2 Hz,
1H), 7.84 (d, J ¼ 5.1 Hz, 1H), 8.23 (d, J ¼ 8.7 Hz, 1H), 8.34 (d,
41.01, 41.18, 99.53, 118.40, 120.30, 124.94, 128.39, 129.87, 131.18,
134.32, 138.93, 149.96, 150.99, 152.76, 156.87, 161.52, 162.98; ESI-
HRMS (m/z) calculated for C23H23ClN6: 418.1673, found: 419.2275
(MþH)þ, 421.2478 (M þ 2)þ; Anal. calcd. for C23H23ClN6: C, 65.94;
H, 5.53; Cl, 8.46; N, 20.06, found: C, 65.88; H, 5.62; Cl, 8.40; N, 20.12.
J ¼ 5.1 Hz, 1H), 9.13 (s, 1H); 13C NMR (100 MHz, DMSO-d6):
d 28.76,
39.50, 41.18, 99.55, 118.41, 120.19, 122.34, 124.95, 128.41, 129.48,
134.33, 141.55, 150.0, 150.98, 152,80, 157.0, 161.54, 162.97; Anal.
calcd. for C22H21ClN6: C, 65.26; H, 5.23; Cl, 8.76; N, 20.76, found: C,
65.26; H, 5.23; Cl, 8.76; N, 20.76.
4.4.13. N2-(3-(7-Chloroquinolin-4-ylamino)propyl)-N4-(4-
methoxyphenyl)pyrimidine-2,4-diamine (8f)
Yield 75%; mp 186e188 ꢀC; IR (KBr, cmꢂ1): 3436, 3234, 3042,
2930, 2836, 1581, 1526, 1510, 1466, 1442, 1419, 1379, 1333, 1285,
1249, 1131, 1037, 975, 903, 878, 851; 1H NMR (400 MHz, DMSO-d6):
4.4.9. N2-(3-(7-Chloroquinolin-4-ylamino)propyl)-N4-(4-
fluorophenyl)pyrimidine-2,4-diamine (8b)
d
1.88e1.92 (m, 2H), 3.29e3.33 (m, 4H), 3.66 (s, 3H, OCH3), 5.89 (d,
Yield 65%; mp 192e195 ꢀC; IR (KBr, cmꢂ1): 3437, 3232, 3042,
2925, 1579, 1525, 1507, 1468, 1445, 1416, 1378, 1235, 1219, 1131, 976,
J ¼ 5.8 Hz, 1H), 6.44 (d, J ¼ 5.8 Hz, 1H), 6.76 (brs, 1H), 6.81 (d,
J ¼ 8.7 Hz, 2H), 7.32 (brs, 1H), 7.41 (dd, J ¼ 2.2, 8.7 Hz, 1H), 7.57 (d,
J ¼ 9.5 Hz, 2H), 7.75 (d, J ¼ 2.2 Hz, 1H), 7.78 (d, J ¼ 5.8 Hz, 1H), 8.23
(d, J ¼ 8.7 Hz, 1H), 8.33 (d, J ¼ 5.8 Hz, 1H), 8.93 (s, 1H); 13C NMR
907, 854, 794; 1H NMR (400 MHz, DMSO-d6):
d 1.84e1.89 (m, 2H),
3.27e3.32 (m, 4H), 5.91 (d, J ¼ 5.8 Hz, 1H), 6.41 (d, J ¼ 5.1 Hz, 1H),
6.83 (brs, 1H), 7.02 (t, J ¼ 8.7 Hz, 2H), 7.30 (brs, 1H), 7.37e7.40 (m,
1H), 7.67e7.70 (m, 2H), 7.73 (d, J ¼ 2.2 Hz, 1H), 7.80 (d, J ¼ 5.8 Hz,
(100 MHz, DMSO-d6):
d 28.82, 39.50, 41.23, 56.08, 99.62, 114.76,
118.46, 122.15, 125.01, 128.47, 134.35, 134.61, 150.05, 151.03, 152.86,
155.25, 161.61, 163.06; ESI-HRMS (m/z) calculated for C23H23ClN6O:
434.1622, found: 435.1425 (MþH)þ, 437.1761 (M þ 2)þ; Anal. calcd.
for C23H23ClN6O: C, 63.52; H, 5.33; Cl, 8.15; N, 19.32; O, 3.68, found:
C, 63.61; H, 5.28; Cl, 8.22; N, 19.37; O, 3.80.
1H), 8.20 (d, J ¼ 8.7 Hz, 1H), 8.30 (d, J ¼ 5.8 Hz, 1H), 9.14 (s, 1H); 13
C
NMR (100 MHz, DMSO-d6):
d 28.76, 39.50, 41.17, 99.57, 115.86,
116.08, 118.42, 121.78, 121.85, 124.94, 124.98, 128.41, 134.37, 137.92,
149.99, 151.02, 152.78, 156.85, 159.22, 161.42, 162.95; ESI-HRMS (m/
z) calculated for C22H20ClFN6: 422.1422, found: 423.1856 (MþH)þ,
425.2231 (M þ 2)þ; Anal. calcd. for C22H20ClFN6: C, 62.48; H, 4.77;
Cl, 8.38; F, 4.49; N, 19.87, found: C, 62.41; H, 4.85; Cl, 8.30; F, 4.53; N,
20.04.
4.4.14. N2-(3-(7-Chloroquinolin-4-ylamino)propyl)-N4-(3,5-
dimethoxyphenyl)pyrimidine-2,4-diamine (8g)
Yield 70%; mp 191e192 ꢀC; IR (KBr, cmꢂ1): 3396, 3239, 3129,
3031, 2998, 2963, 1580, 1544, 1480, 1449, 1420, 1374, 1329, 1220,
1207, 1152, 1061, 982, 869; 1H NMR (400 MHz, DMSO-d6):
4.4.10. N4-(4-Chlorophenyl)-N2-(3-(7-chloroquinolin-4-ylamino)
propyl)pyrimidine-2,4-diamine (8c)
d
1.91e1.94 (m, 2H), 3.30e3.40 (m, 4H), 3.68 (s, 6H, 2OCH3), 5.97 (d,
Yield 72%; mp 181e183 ꢀC; IR (KBr, cmꢂ1): 3433, 3248, 3087,
2927, 1609, 1582, 1549, 1490, 1332, 1237, 1139, 1085, 981, 902, 875,
J ¼ 5.8 Hz, 1H), 6.09 (brs, 1H), 6.44 (d, J ¼ 5.1 Hz, 1H), 6.90 (brs, 1H),
7.0 (brs, 2H), 7.31 (brs, 1H), 7.41 (dd, J ¼ 2.2, 8.7 Hz, 1H), 7.76 (d,
J ¼ 2.2 Hz, 1H), 7.84 (d, J ¼ 5.1 Hz, 1H), 8.23 (d, J ¼ 8.7 Hz, 1H), 8.34
(d, J ¼ 5.1 Hz, 1H), 9.11 (s, 1H); 13C NMR (100 MHz, DMSO-d6):
853, 790; 1H NMR (400 MHz, DMSO-d6):
d 1.90e1.93 (m, 2H),
3.31e3.33 (m, 4H), 5.97 (d, J ¼ 5.1 Hz, 1H), 6.44 (d, J ¼ 5.1 Hz, 1H),
6.91 (brs, 1H), 7.24 (d, J ¼ 8.0 Hz, 2H), 7.34 (brs, 1H), 7.41 (d,
J ¼ 8.0 Hz, 1H), 7.76 (brs, 3H), 7.86 (d, J ¼ 5.1 Hz, 1H), 8.23 (d,
J ¼ 8.7 Hz, 1H), 8.34 (d, J ¼ 4.3 Hz, 1H), 9.28 (s, 1H); 13C NMR
d
28.64, 40.99, 41.10, 55.83, 94.51, 98.31, 99.49, 118.34, 124.89,
128.33, 134.23, 143.15, 149.92, 150.93, 152.73, 161.31, 161.48, 162.86;
ESI-HRMS (m/z) calculated for C24H25ClN6O2: 464.1728, found:
(100 MHz, DMSO-d6):
d
28.70, 39.50, 41.13, 99.52, 118.36, 121.42,
465.0541 (MþH)þ, 467.0970 (M
þ
2)þ; Anal. calcd. for
C24H25ClN6O2: C, 62.00; H, 5.42; Cl, 7.63; N, 18.08; O, 6.88, found: C,
124.93, 125.68, 128.36, 129.23, 134.32, 140.53, 149.92, 150.96,
152.70, 161.24, 162.85; Anal. calcd. for C22H20Cl2N6: C, 60.14; H,
4.59; Cl, 16.14; N, 19.13, found: C, 60.26; H, 4.53; Cl, 16.30; N, 19.22.
61.89; H, 5.55; Cl, 7.60; N, 18.17; O, 7.01.
4.4.15. N2-(4-(7-Chloroquinolin-4-ylamino)butyl)-N4-
phenylpyrimidine-2,4-diamine (9a)
4.4.11. N4-(4-Bromophenyl)-N2-(3-(7-chloroquinolin-4-ylamino)
propyl)pyrimidine-2,4-diamine (8d)
Yield 70%; mp 190e192 ꢀC; IR (KBr, cmꢂ1): 3417, 3238, 3001,
2935, 2863, 1585, 1544, 1497, 1428, 1347, 1234, 1131, 975, 902, 852,
Yield 50%; mp 203e242 ꢀC; IR (KBr, cmꢂ1): 3422, 3185, 2927,
1578, 1489, 1394, 1329, 1233, 1136, 1072, 1004, 979, 901, 853, 795;
799; 1H NMR (400 MHz, DMSO-d6):
d 1.66e1.70 (m, 4H), 3.24e3.31
1H NMR (400 MHz, DMSO-d6)
d
d
:
1H NMR (400 MHz, DMSO-d6)
1.90e1.93 (m, 2H), 3.31e3.33 (m,
d:
(m, 4H), 5.96 (d, J ¼ 5.8 Hz, 1H), 6.43 (d, J ¼ 5.1 Hz, 1H), 6.78 (brs,
1H), 6.89 (t, J ¼ 7.3 Hz, 1H), 7.22 (t, J ¼ 5.1 Hz, 2H), 7.29 (t, J ¼ 5.1 Hz,
1H), 7.40 (dd, J ¼ 2.2, 8.7 Hz, 1H), 7.71 (d, J ¼ 8.0 Hz, 2H), 7.75 (d,
J ¼ 1.4 Hz, 1H), 7.81 (d, J ¼ 5.1 Hz, 1H), 8.24 (d, J ¼ 8.7 Hz, 1H), 8.34
(d, J ¼ 5.1 Hz, 1H), 9.10 (s, 1H); 13C NMR (100 MHz, DMSO-d6):
1H NMR (400 MHz, DMSO-d6):
4H), 5.97 (d, J ¼ 5.1 Hz, 1H), 6.44 (d, J ¼ 5.1 Hz, 1H), 6.91 (brs, 1H),
7.24 (d, J ¼ 8.0 Hz, 2H), 7.34 (brs, 1H), 7.41 (d, J ¼ 8.0 Hz, 1H), 7.76
(brs, 3H), 7.86 (d, J ¼ 5.1 Hz, 1H), 8.23 (d, J ¼ 8.7 Hz, 1H), 8.33 (d,
J ¼ 5.8 Hz, 1H), 9.27 (s, 1H); ESI-HRMS (m/z) calculated for
d
25.43, 26.93, 40.46, 42.28, 98.62, 117.46, 119.16, 121.32, 123.94,