B. Insuasty et al. / European Journal of Medicinal Chemistry 60 (2013) 1e9
5
(400 MHz, DMSO-d6)
d
(ppm): 2.13 (s, 3H, NCH3), 2.23 (s, 3H, CH3),
4.41 (s, 1H, 5-CH), 6.54e6.57 (m, 4H, AreH), 7.01 (s, 1H, ]CH), 8.41
(s, 1H, NH), 11.96 (br s, 1H, NH); 13C NMR (100 MHz, DMSO-d6)
2.31 (s, 3H, CH3), 2.53 (s, 3H, SCH3), 2.71 (d, J ¼ 16.2 Hz, 1H, CH2),
2.96 (d, J ¼ 16.2 Hz, 1H, CH2), 3.18 (d, J ¼ 13.4 Hz, 1H, CH2), 3.42 (d,
J ¼ 13.4 Hz, 1H, CH2), 4.38 (s, 1H, 5-CH), 7.03 (s, 1H, ]CH), 7.05 (d,
J ¼ 7.9 Hz, 2H, AreH), 7.12 (d, J ¼ 7.9 Hz, 2H, AreH), 7.16 (d,
J ¼ 8.3 Hz, 2H, AreH), 7.20 (d, J ¼ 8.3 Hz, 2H, AreH), 8.43 (s, 1H, NH),
d
(ppm): 13.3 (SCH3), 41.9 (C-5), 45.6 (NCH3), 54.4 (2CH2), 56.5
(2OCH3), 56.6 (2OCH3), 60.3 (OCH3), 60.4 (OCH3), 107.6 (2CH), 109.0
(C), 115.4 (2CH), 123.8 (C), 125.2 (]CH), 127.1 (C), 128.6 (C), 130.5
(C), 134.7 (C), 138.7 (C), 141.0 (C), 152.8 (2C), 155.0 (2C), 156.1 (C),
157.2 (C), 162.2 (C); MS (EI): m/z 478 (100), 441 (2, [etriOCH3C6H2]),
399 (11), 311 (45), 170 (21), 74 (35). Anal. Calcd. For C31H36N4O7S
(608.2): C, 61.17; H, 5.96; N, 9.20; S, 5.27. Found: C, 61.23; H, 6.05; N,
9.27; S, 5.31.
11.91 (br s, 1H, NH); 13C NMR (100 MHz, DMSO-d6)
d (ppm): 13.1
(SCH3), 21.1 (CH3), 21.3 (CH3), 41.0 (C-5), 45.2 (NCH3), 54.7 (CH2),
56.6 (CH2), 93.9 (C), 114.2 (C), 121.8 (]CH), 127.5 (C), 127.9 (2CH),
128.5 (C), 129.2 (2CH), 129.4 (2CH), 129.5 (2CH), 134.2 (C), 135.7 (C),
136.5 (C), 143.4 (C), 154.1 (C), 159.8 (C), 162.1 (C); MS (EI): m/z 394
(16), 380 (18), 365 (0.4, [eCH3C6H4]), 261 (4), 247 (5), 94 (33), 79
(23), 47 (100), 28 (71). Anal. Calcd. For C27H28N4OS (456.2): C, 71.02;
H, 6.18; N, 12.27; S, 7.02. Found: C, 71.10; H, 6.22; N, 12.35; S, 7.09.
4.2.8. (E)-9-(4-Chlorobenzylidene)-5-(4-chlorophenyl)-7-ethyl-2-
(methylthio)-5,6,7,8,9,10-hexahydropyrimido[4,5-b][1,6]
naphthyridin-4(3H)-one (5a)
It was obtained from 2a in 86% yield; mp 247e249 ꢀC; FTIR (KBr)
4.2.5. (E)-9-(4-Methoxybenzylidene)-5-(4-methoxyphenyl)-7-
methyl-2-(methylthio)-6,7,8,9-tetrahydropyrimido[4,5-b][1,6]
naphthyridin-4(3H,5H,10H)-one (4e)
y
¼ 3410 (NH), 2933, 1635 (C]O), 1509, 1238, 1091 cmꢁ1; 1H NMR
(400 MHz, DMSO-d6)
d
(ppm): 0.84 (t, J ¼ 7.0 Hz, 3H, NCH2CH3),
2.21e2.37 (m, 2H, NCH2CH3), 2.53 (s, 3H, SCH3), 2.70 (d, J ¼ 16.4 Hz,
1H, CH2), 3.08 (d, J ¼ 16.4 Hz, 1H, CH2), 3.19 (d, J ¼ 13.6 Hz, 1H, CH2),
3.48 (d, J ¼ 13.6 Hz, 1H, CH2), 4.46 (s, 1H, 5-CH), 7.05 (s, 1H, ]CH),
7.23e7.27 (m, 2H, AreH), 7.27e7.35 (m, 4H, AreH), 7.44 (d,
J ¼ 7.8 Hz, 2H, AreH), 8.50 (s, 1H, NH), 12.03 (br s, 1H, NH); 13C NMR
It was obtained from 1e in 55% yield; mp 203e205 ꢀC; FTIR (KBr)
y
¼ 3410 (NH), 2936, 1633 (C]O), 1507, 1255, 1033 cmꢁ1; 1H NMR
(400 MHz, DMSO-d6) d (ppm): 2.58 (s, 3H, NCH3), 2.75 (s, 3H, SCH3),
3.15 (d, J ¼ 16.2 Hz, 1H, CH2), 3.44 (d, J ¼ 16.2 Hz, 1H, CH2), 3.70 (d,
J ¼ 12.7 Hz, 1H, CH2), 3.83 (s, 6H, 2OCH3), 3.93 (d, J ¼ 12.7 Hz, 1H,
CH2), 4.41 (s, 1H, 5-CH), 7.01 (d, J ¼ 8.5 Hz, 2H, AreH), 7.07 (d,
J ¼ 8.8 Hz, 2H, AreH), 7.10e7.14 (m, 3H, AreH and ]CH), 7.48 (d,
J ¼ 8.5 Hz, 2H, AreH), 8.27 (s, 1H, NH), 12.48 (br s, 1H, NH); 13C NMR
(100 MHz, DMSO-d6)
d (ppm): 12.5 (NCH2CH3), 13.1 (SCH3), 41.0
(C-5), 50.8 (NCH2CH3), 52.2 (CH2), 54.1 (CH2), 93.4 (C), 114.2 (C),
121.0 (]CH), 128.0 (C), 128.6 (2CH), 128.8 (2CH), 129.7 (C), 129.8
(2CH), 131.3 (2CH),131.3 (C), 131.8 (C), 136.0 (C), 145.1 (C), 154.0 (C]
O), 160.1 (C), 162.0 (C); MS (EI): m/z 514/512/510 (16/32/53, [M]þ),
513/511/509 (18/74/100, [M ꢁ H]þ), 401/399 (12/32, [eClC6H4]),
385 (19), 369 (13), 124 (15), 111 (14), 57 (27), 44 (59), 43 (52).
Anal. Calcd. For C26H24Cl2N4OS (510.1): C, 61.06; H, 4.73; N, 10.95; S,
6.27. Found: C, 61.12; H, 4.85; N, 11.05; S, 6.30.
(100 MHz, DMSO-d6) d (ppm): 12.8 (SCH3), 42.2 (C-5), 45.5 (NCH3),
52.5 (CH2), 54.2 (CH2), 55.0 (OCH3), 55.3 (OCH3), 99.4 (C), 113.6
(2CH), 114.3 (2CH), 116.8 (C), 120.7 (]CH), 125.6 (C), 128.8 (2CH),
129.8 (C), 130.6 (C), 131.8 (2CH), 138.4 (C), 151.2 (C), 151.8 (C), 158.8
(C), 160.0 (C), 162.0 (C); MS (EI): m/z 381 (1, [eOCH3C6H4]), 358
(100), 339 (8), 251 (17), 170 (40), 74 (33), 43 (15). Anal. Calcd. For
C
27H28N4O3S (488.2): C, 66.37; H, 5.78; N, 11.47; S, 6.56. Found: C,
4.2.9. (E)-9-(4-Bromobenzylidene)-5-(4-bromophenyl)-7-ethyl-2-
(methylthio)-6,7,8,9-tetrahydropyrimido[4,5-b][1,6]naphthyridin-
4(3H,5H,10H)-one (5b)
66.45; H, 5.83; N, 11.52; S, 6.61.
4.2.6. (E)-5-(Benzo[d][1,3]dioxol-5-yl)-9-(benzo[d][1,3]dioxol-5-
ylmethylene)-7-methyl-2-(methylthio)-6,7,8,9-tetrahydropyrimido
[4,5-b][1,6]naphthyridin-4(3H,5H,10H)-one (4f)
It was obtained from 2b in 85% yield; mp 251e253 ꢀC; FTIR
(KBr)
y
¼ 3396 (NH), 2931, 1634 (C]O), 1507, 1237, 1096 cmꢁ1; 1H
NMR (400 MHz, DMSO-d6)
d
(ppm): 0.85 (t, J ¼ 7.0 Hz, 3H,
It was obtained from 1f in 63% yield; mp 187e190 ꢀC; FTIR (KBr)
NCH2CH3), 2.22e2.37 (m, 2H, NCH2CH3), 2.53 (s, 3H, SCH3), 2.70 (d,
J ¼ 16.4 Hz, 1H, CH2), 3.08 (d, J ¼ 16.4 Hz, 1H, CH2), 3.19 (d,
J ¼ 13.8 Hz, 1H, CH2), 3.49 (d, J ¼ 13.8 Hz, 1H, CH2), 4.45 (s, 1H, 5-
CH), 7.03 (s, 1H, ]CH), 7.20 (d, J ¼ 8.5 Hz, 2H, AreH), 7.24 (d,
J ¼ 8.5 Hz, 2H, AreH), 7.46 (d, J ¼ 8.5 Hz, 2H, AreH), 7.58 (d,
J ¼ 8.5 Hz, 2H, AreH), 8.49 (s, 1H, NH), 11.99 (br s, 1H, NH); 13C NMR
y
¼ 3423 (NH), 2884, 1635 (C]O), 1503, 1234, 1037 cmꢁ1; 1H NMR
(400 MHz, DMSO-d6) d (ppm): 2.16 (s, 3H, NCH3), 2.40 (s, 3H, SCH3),
2.75 (d, J ¼ 15.9 Hz, 1H, CH2), 2.93 (d, J ¼ 15.9 Hz, 1H, CH2), 3.19 (d,
J ¼ 13.6 Hz,1H, CH2), 3.37e3.44 (m,1H, CH2), 4.32 (s,1H, 5-CH), 5.92
(m, 2H, OCH2O), 6.03 (s, 2H, OCH2O), 6.68e6.72 (m, 1H, AreH),
6.73e6.78 (m, 3H, AreH), 6.83 (s, 1H, AreH), 6.90 (s, 1H, ]CH),
6.93 (d, J ¼ 8.0 Hz, 1H, AreH), 7.83 (s, 1H, NH), not observed (1H,
(100 MHz, DMSO-d6) d (ppm): 12.5 (NCH2CH3), 13.1 (SCH3), 41.1 (C-
5), 50.8 (NCH2CH3), 52.2 (CH2), 54.1 (CH2), 93.3 (C), 114.1 (C), 119.8
(C), 120.4 (C), 121.1 (]CH), 128.1 (C), 129.7 (C), 130.2 (2CH), 131.5
(2CH), 131.6 (2CH), 131.7 (2CH), 136.4 (C), 145.6 (C), 154.0 (C), 160.2
(C), 162.3 (C); MS (EI): m/z 603/601/599 (3/20/41, [M þ H]þ), 602/
600/598 (8/19/15, [M]þ), 445/443 (6/11, [eBrC6H4]), 429 (11), 262
(8), 168 (17), 152 (24), 57 (42), 44 (100), 43 (86). Anal. Calcd. For
NH); 13C NMR (100 MHz, DMSO-d6)
d (ppm): 13.3 (SeCH3), 41.6 (C-
5), 45.5 (NeCH3), 54.9 (CH2), 56.8 (CH2), 94.1 (C), 101.0 (OCH2O),
101.5 (OCH2O), 108.1 (CH), 108.6 (CH), 108.7 (CH), 109.6 (CH), 113.5
(C), 120.8 (CH), 121.0 (]CH), 123.5 (CH), 128.0 (C), 128.5 (C), 131.4
(C), 141.5 (C), 145.7 (C), 146.4 (C), 147.3 (C), 147.7 (C), 154.4 (C), 162.4
(C), 167.0 (C); MS (EI): m/z 395 (2, [eOCH2OC6H3]), 386 (100), 353
(12), 170 (33), 74 (40), 43 (18). Anal. Calcd. For C27H24N4O5S (516.2):
C, 62.78; H, 4.68; N, 10.85; S, 6.21. Found: C, 62.86; H, 4.74; N, 10.92;
S, 6.28.
C
26H24Br2N4OS (598.0): C, 52.01; H, 4.03; N, 9.33; S, 5.34. Found: C,
52.09; H, 4.11; N, 9.42; S, 5.40.
4.2.10. (E)-7-Ethyl-2-(methylthio)-9-(4-nitrobenzylidene)-5-(4-
nitrophenyl)-6,7,8,9-tetrahydropyrimido[4,5-b][1,6]naphthyridin-
4(3H,5H,10H)-one (5c)
4.2.7. (E)-7-Methyl-2-(methylthio)-9-(3,4,5-trimethoxybenzylidene)-
5-(3,4,5-trimethoxyphenyl)-6,7,8,9-tetrahydropyrimido[4,5-b][1,6]
naphthyridin-4(3H,5H,10H)-one (4g)
It was obtained from 2c in 71% yield; mp 225e227 ꢀC; FTIR (KBr)
y
¼ 3321 (NH), 2923, 1630 (C]O), 1514, 1343, 1241, 1090 cmꢁ1
;
1H
It was obtained from 1g in 49% yield; mp 183e185 ꢀC; FTIR (KBr)
NMR (400 MHz, DMSO-d6)
d
(ppm): 0.85 (t, J ¼ 7.2 Hz, 3H, NCH2CH3),
y
¼ 3378 (NH), 2938, 1639 (C]O), 1504, 1237, 1125 cmꢁ1; 1H NMR
2.25e2.41(m, 2H,NCH2CH3),2.54(s,3H, SCH3),2.69(d,J¼16.7 Hz,1H,
CH2), 3.17 (d, J ¼ 16.7 Hz, 1H, CH2), 3.26(d, J ¼ 13.8 Hz, 1H, CH2), 3.56 (d,
J ¼ 13.8 Hz, 1H, CH2), 4.68 (s, 1H, 5-CH), 7.23 (s, 1H, ]CH), 7.53 (d,
J ¼ 8.8 Hz, 2H, AreH), 7.56 (d, J ¼ 8.8 Hz, 2H, AreH), 8.17 (d, J ¼ 8.8 Hz,
2H, AreH), 8.25 (d, J ¼ 8.8 Hz, 2H, AreH), 8.62 (s, 1H, NH), 12.10 (br s,
(400 MHz, DMSO-d6) d (ppm): 2.20 (s, 3H, NCH3), 2.54 (s, 3H, SCH3),
2.80 (d, J ¼ 16.2 Hz, 1H, CH2), 3.00 (d, J ¼ 16.2 Hz, 1H, CH2), 3.30 (d,
J ¼ 13.8 Hz, 1H, CH2), 3.51 (d, J ¼ 13.8 Hz, 1H, CH2), 3.63 (s, 3H,
OCH3), 3.69 (s, 3H, OCH3), 3.71 (s, 6H, 2OCH3), 3.79 (s, 6H, 2OCH3),