C. Sun et al. / European Journal of Medicinal Chemistry 46 (2011) 11e20
17
5.4.6. 1-(6-Chloro-3-pyridinemethyl)-5-(3-methyl-1-
7.82e7.79 (1H, dd, J ¼ 2.4 Hz, 2.4 Hz, pyridine-H), 7.37e7.35 (1H, d,
J ¼ 8 Hz, pyridine-H), 4.77e4.73 (1H, d, J ¼ 15.2 Hz, CH2-pyridine),
4.63e4.60 (1H, m, CH2-pyridine), 4.51e4.36 (4H, m, triazine-4H),
4.22e4.03 (2H, m, OCH2), 3.66e3.63 (1H, t, J ¼ 7.2 Hz, CHC]O),
2.53e2.46 (2H, m, SCH2), 2.08 (3H, s, SCH3), 2.02e1.91 (2H, m, CH2),
1.28e1.25 (3H, t, J ¼ 7.2 Hz, OCH2CH3). IR (potassium bromide,
ethoxycarbonylbutyl)-1,3,5-hexahydrotriazine-2-N-nitroimine (4f)
White crystals, yield 50.2%, m.p.104e106 ꢀC. 1H NMR (
d, ppm,
CDCl3): 9.67 (1H, s, NH), 8.33 (1H, d, J ¼ 2 Hz, pyridine-H), 7.83e7.80
(1H, dd, J ¼ 2.4 Hz, 2.4 Hz, pyridine-H), 7.37e7.35 (1H, d, J ¼ 8 Hz,
pyridine-H), 4.77e4.73 (1H, d, J ¼ 15.6 Hz, CH2-pyridine), 4.64e4.60
(1H, dd, J ¼ 2.4 Hz, 2.4 Hz, CH2-pyridine), 4.47e4.29 (4H, m,
triazine-4H), 4.16e4.07 (2H, m, OCH2), 3.48e3.45 (1H,m, CHC]O),
1.64e1.51 (2H, m, CH2), 1.49e1.42 (1H, m, CH), 1.28e1.24 (3H,t,
J ¼ 7.2 Hz, OCH2CH3), 0.90e0.89 (3H, d, J ¼ 2.4 Hz, CHCH3),
cmꢁ1
) n: 3394 (NeH),2980 (pyridine),1734 (C]O),1544 (C]N),1398
(NO2), 1193 (CeOeC), 1094 (CeN). Anal. calcd for C16H23ClN6O4S: C
44.60, H 5.38, N 19.50; found C 44.53, H 5.43, N 19.55. ESI-MS
20
(M þ H) m/z: 431.2, [
a]
¼ ꢁ3.73 (c ¼ 0.1 g/L in acetone).
D
0.89e0.88 (3H, d, J ¼ 2 Hz, CHCH3). IR (potassium bromide, cmꢁ1
) n:
3259 (NeH), 2961 (pyridine), 1742 (C]O), 1587 (C]N), 1397 (NO2),
1186 (CeOeC), 1105 (CeN). Anal. calcd for C17H25ClN6O4: C 49.45, H
5.4.11. 1-(2-Chloro-5-thiazomethyl)-5-(1-(4-chlorophenyl)-1-
ethyoxycarbonylmethyl)-1,3,5-hexahydrotriazine-2-N-nitroimine
(4k)
6.10, N 20.36; found C 49.52, H 6.14, N 27.35. ESI-MS (M þ H) m/z:
20
413.4, [
a
]
¼ ꢁ5.97 (c ¼ 0.1 g/L in acetone).
White crystals, yield 44.7%, m.p.226e228 ꢀC. 1H NMR(
d, ppm,
D
CDCl3): 9.41 (1H, d, J ¼ 0.8 sHz, NH), 7.37 (1H, s, thiazole-H), 7.35
(1H, s, phenyl-H), 7.30 (1H, s, phenyl-H), 7.24e7.22 (2H, d,
J ¼ 8.8 Hz, phenyl-H), 4.64e4.60 (1H, d, J ¼ 15.6 Hz, CH2-thiazole),
4.48e4.46 (1H, d, J ¼ 16 Hz, CH2-thiazole), 4.41e4.27 (4H, m,
triazine-4H), 4.09e4.05 (2H, m, OCH2), 1.59 (1H, t, J ¼ 6.8 Hz, CHC]
5.4.7. 1-(2-Chloro-5-thiazomethyl)-5-(2-methyl-1-
ethoxycarbonylbutyl)-1,3,5-hexahydrotriazine-2-N-nitroimine (4g)
White crystals, yield 45.3%, m.p.135e137 ꢀC. 1H NMR (
d, ppm,
CDCl3): 9.52 (1H, d, J ¼ 0.8 Hz, NH), 7.46 (1H, s, thiazole-H),
4.74e4.70 (1H, d, J ¼ 15.6 Hz, CH2-thiazole), 4.63e4.59 (1H, dd,
J ¼ 2 Hz, 2.4 Hz, CH2-thiazole), 4.53e4.49 (2H, m, triazine-2H),
4.43e4.39 (2H, m, triazine-2H), 4.19e4.04 (2H, m, OCH2), 3.13e3.11
(1H, d, J ¼ 9.6 Hz, CHC]O), 1.61e1.55 (2H, m, CH2), 1.27e1.24 (3H, t,
J ¼ 6.8 Hz, OCH2CH3),1.17e1.13 (1H, t, J ¼ 7.2 Hz, CH), 0.91e0.87 (6H,
O), 1.15e1.11 (3H, t, J ¼ 7.2 Hz, OCH3). IR (potassium bromide, cmꢁ1
)
n
: 3254 (NeH), 2965 (thiazole), 1740 (C]O), 1590 (C]N), 1399
(NO2), 1190 (CeOeC), 1053 (CeN). Anal. calcd for C18H19Cl2N6O4S: C
43.14, H 3.83, N 17.75; found C 43.09, H 3.89, N 17.81. ESI-MS
20
(M þ H) m/z: 473.3 [
a
]
¼ ꢁ12.75 (c ¼ 0.1 g/L in acetone).
D
m, 2CH3). IR (potassium bromide, cmꢁ1
) n: 3291 (NeH), 2972
(thiazole), 1733 (C]O), 1585 (C]N), 1395 (NO2), 1195 (CeOeC),
1046 (CeN). Anal. calcd for C15H23ClN6O4S: C 43.01, H 5.53, N 20.06;
5.4.12. 1-(6-Chloro-3-pyridinemethyl)-5-(1-(4-chlorophenyl)-1-
ethyoxycarbonylmethyl)-1,3,5-hexahydrotriazine-2-N-nitroimine
(4l)
found C 42.95, H 5.58, N 20.17. ESI-MS (M þ H) m/z: 419.1
20
[
a]
¼ þ11.53 (c ¼ 0.1 g/L in acetone).
White crystals, yield 41.5%, m.p.160e162 ꢀC. 1H NMR (
d, ppm,
D
CDCl3): 9.56 (1H, s, NH), 8.23 (1H, d, J ¼ 2.4 Hz, pyridine-H), 7.81e7.78
(1H, dd, J ¼ 2 sHz, 2.4 Hz, pyridine-H), 7.37e7.35 (1H, d, J ¼ 7.6 sHz,
pyridine-H), 7.33 (1H, s, phenyl-H), 7.28 (1H, s, phenyl-H), 7.24e7.22
(2H, d, J ¼ 8.4 Hz, phenyl-H), 4.60e4.56 (1H, d, J ¼ 15.2 Hz, CH2-
pyridine), 4.51e4.48 (1H, dd, J ¼ 0.4 Hz, 0.4 Hz, CH2-pyridine),
4.45e4.23 (4H, m, triazine-4H), 4.12e4.01 (2H, m, OCH2),1.27 (1H, s,
CHC]O), 1.14e1.11 (3H, t, J ¼ 7.2 Hz, CH3). IR (potassium bromide,
5.4.8. 1-(6-Chloro-3-pyridinemethyl)-5-(2-methyl-1-
ethoxycarbonylbutyl)-1,3,5-hexahydrotriazine-2-N-nitroimine (4h)
White crystals, yield 43.9%, m.p.141e143 ꢀC. 1H NMR (
d, ppm,
CDCl3): 9.66 (1H, s, NH), 8.33e8.32 (1H, d, J ¼ 6.4 Hz, pyridine-H),
7.82e7.79 (1H, dd, J ¼ 2.4 Hz, 2.4 Hz, pyridine-H), 7.37e7.35 (1H, d,
J ¼ 8 Hz, pyridine-H), 4.81e4.77 (1H, d, J ¼ 15.6 Hz, CH2-pyridine),
4.64e4.60 (1H, dd, J ¼ 2.4 Hz, 2.4 Hz, CH2-pyridine), 4.47e4.29
(4H, m, triazine-4H), 4.19e4.06 (2H, m, OCH2), 3.12e3.09 (1H, d,
J ¼ 9.6 Hz, CHC]O), 1.59 (3H, s, CHCH2), 1.28e1.25 (3H, t,
J ¼ 7.2 Hz, OCH2CH3), 0.89e0.85 (6H, m, 2CH3). IR (potassium
cmꢁ1
)n:3342(NeH), 2985(pyridine),1727(C]O),1545(C]N),1397
(NO2), 1193 (CeOeC), 1112 (CeN). Anal. calcd for C20H21Cl2N6O4: C
48.83, H 4.31, N 17.98; found C 48.78, H 4.38, N 18.02. ESI-MS (M þ H)
20
m/z: 467.3 [
a
]
¼ ꢁ22.50 (c ¼ 0.1 g/L in acetone).
D
bromide, cmꢁ1
) n: 3288 (NeH), 2965 (pyridine), 1732 (C]O), 1585
(C]N), 1396 (NO2), 1189 (CeOeC), 1106 (CeN). Anal. calcd for
5.4.13. 1-(2-Chloro-5-thiazomethyl)-5-(2-pheny-1-
ethyoxycarbonylethyl)-1,3,5-hexahydrotriazine-2-N-nitroimine
(4m)
C17H25ClN6O4: C 49.45, H 6.10 1, N 20.36; found C 49.40, H 6.18, N
20
20.40 ESI-MS (M þ H) m/z: 413.5, [
a
]
¼ ꢁ6.48 (c ¼ 0.1 g/L in
D
acetone).
White crystals, yield 52.8%, m.p.106e108 ꢀC. 1H NMR(
d, ppm,
CDCl3): 9.50 (1H, d, J ¼ 0.8 Hz, NH), 7.46 (1H, s, thiazole-H), 7.30e7.25
(3H, m, phenyl-H), 7.11e7.09 (2H, m, phenyl-H), 4.63e4.59 (2H, m,
CH2-thiazole), 4.56e4.51 (4H, m, triazine-4H), 4.07e3.90 (2H, m,
OCH2), 3.69e3.65 (1H, m, CHC]O), 3.06e2.94 (2H, m, CH2Ph),
5.4.9. 1-(2-Chloro-5-thiazomethyl)-5-(3-meththioyl-1-
ethoxycarbonylpropyl)-1,3,5-hexahydrotriazine-2-N-nitroimine (4i)
White crystals, yield 35.8%, m.p.89e91 ꢀC. 1H NMR (
d, ppm,
CDCl3): 9.55 (1H, d, J ¼ 0.8 Hz, NH), 7.47 (1H, s, thiazole-H),
4.72e4.68 (1H, d, J ¼ 16 Hz, CH2-thiazole), 4.62e4.57 (1H, m, CH2-
thiazole), 4.53e4.45 (4H, m, triazine-4H), 4.21e4.04 (2H, m, OCH2),
3.65e3.62 (1H, t, J ¼ 6.8 Hz, CHC]O), 2.57e2.45 (2H, m, SCH2), 2.09
(3H, s, CH3), 2.02e1.95 (2H, m, CH2), 1.28e1.25 (3H, t, J ¼ 7.2 Hz,
1.09e1.05 (3H, t, J ¼ 7.2 Hz, OCH3). IR (potassium bromide, cmꢁ1
) n:
3289 (NeH), 2962 (thiazole), 1729 (C]O), 1585 (C]N), 1396 (NO2),
1189 (CeOeC),1049 (CeN). Anal. calcd for C18H21ClN6O4S: C 47.73, H
4.67, N 18.56; found C 47.80, H 4.72, N 18.52. ESI-MS (M þ H) m/z:
20
453.6, [
a
]
¼ þ13.67 (c ¼ 0.1 g/L in acetone).
D
OCH2CH3). IR (potassium bromide, cmꢁ1
) n: 3395 (NeH), 3008
(thiazole), 1744 (C]O), 1589 (C]N), 1396 (NO2), 1197 (CeOeC),
1108 (CeN). Anal. calcd for C14H21ClN6O4S2: C 38.48, H 4.84, N
5.4.14. 1-(6-Chloro-3-pyridinemethyl)-5-(2-pheny-1-
ethyoxycarbonylethyl)-1,3,5-hexahydrotriazine-2-N-nitroimine (4n)
19.23; found C 38.39, H 4.89, N 19.31. ESI-MS (M þ H) m/z: 437.6,
White crystals, yield 50.5%, m.p.131e133 ꢀC. 1H NMR (
d, ppm,
20
[
a]
¼ þ8.48 (c ¼ 0.1 g/L in acetone).
CDCl3): 9.64 (1H, s, NH), 8.32 (1H, d, J ¼ 2 Hz, pyridine-H), 7.82e7.79
(1H, dd, J ¼ 2.4 Hz, 2.4 Hz, pyridine-H), 7.36e7.34 (1H, d, J ¼ 7.6 Hz,
pyridine-H), 7.30e7.25 (3H, m, phenyl-H), 7.12e7.10 (2H, t, J ¼ 2 Hz,
phenyl-H), 4.65e4.60 (2H, m, CH2-pyridine), 4.54e4.38 (4H, m,
triazine-4H), 4.09e3.92 (2H, m, OCH2), 3.71e3.67 (1H, m, CHC ¼ O),
3.06e2.92 (2H, m, CH2Ph), 1.11e1.08 (3H, t, J ¼ 7.2 Hz, CH3). IR
D
5.4.10. 1-(6-Chloro-3-pyridinemethyl)-5-(2-methanthioyl-1-
ethoxycarbonylpropyl)-1,3,5-hexahydrotriazine-2-N-nitroimine (4j)
White crystals, yield 33.6%, m.p.68e70 ꢀC. 1H NMR (
d, ppm,
CDCl3): 9.68 (1H, s, NH), 8.43e8.33 (1H, d, J ¼ 2.4 Hz, pyridine-H),