L.-P. Guan et al. / European Journal of Medicinal Chemistry 45 (2010) 1746–1752
1751
3.4.6. 6-Nonyloxy-[1,2,4]triazolo[4,3-b]pyridazine (2f)
Yield: 58%; oil. 1H NMR (CDCl3):
8.82 (1H, s, triazolo-H), 7.93
J ¼ 9.8 Hz, pyridazine-H), 6.96–7.16 (4H, m, –C6H4). 13C NMR
d
(CDCl3): d 55.62, 114.83, 116.34, 122.11, 126.86, 138.74, 142.89,
(1H, d, J ¼ 9.8 Hz, pyridazine-H), 6.76 (1H, d, J ¼ 9.8 Hz, pyridazine-
147.52, 154.16, 160.85. IR (KBr) cmꢀ1: 1587 (C]C), 1620 (C]N),
1251,1028 (C–O–C),1175 (N–N). MS m/z: 243(M þ 1). Anal. Calcd for
C12H10N4O2: C, 59.50; H, 4.16; N, 23.13. Found: C, 59.40; H, 3.98; N,
23.04.
H), 4.29 (2H, t, J ¼ 6.5 Hz, –OCH2), 1.25–1.82 (14H, m, –(CH2)7), 0.85
(3H, t, J ¼ 6.7 Hz, –CH3). 13C NMR (CDCl3):
d 14.05, 22.53, 26.06,
29.57, 29.81, 30.19, 30.44, 30.78, 68.61, 117.29, 125.65, 138.43,
142.82, 160.89 . IR (KBr) cmꢀ1: 1587 (C]C), 1624 (C]N), 1251, 1024
(C–O–C), 1170 (N–N). MS m/z: 263(M þ 1). Anal. Calcd for
C14H22N4O: C, 64.09; H, 8.45; N, 21.36. Found: C, 63.89; H, 8.32; N,
21.34.
3.4.13. 6-(2-Chlorophenoxy)-[1,2,4]triazolo[4,3-b]pyridazine (2m)
Yield: 60.5%; m.p.: 150–153 ꢂC. 1H NMR (CDCl3):
d 8.77 (1H, s,
triazolo-H), 8.15 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.08 (1H, d,
J ¼ 9.8 Hz, pyridazine-H), 7.13–7.55 (4H, m, –C6H4). 13C NMR
3.4.7. 6-Decyloxy-[1,2,4]triazolo[4,3-b]pyridazine (2g)
(CDCl3): d 115.73, 123.50, 127.27, 128.19, 129.56, 130.85, 138.66,
Yield: 60%; m.p.: 79–81 ꢂC. 1H NMR (CDCl3):
d
8.85 (1H, s, tri-
142.95, 148.17, 160.19, 165.03. IR (KBr) cmꢀ1: 1586 (C]C), 1621
(C]N), 1252, 1029 (C–O–C), 1174 (N–N). MS m/z: 247(M þ 1). Anal.
Calcd for C11H7ClN4O: C, 53.56; H, 2.86; N, 22.71. Found: C, 53.43; H,
2.78; N, 22.67.
azolo-H), 7.95 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 6.78 (1H, d,
J ¼ 9.8 Hz, pyridazine-H), 4.32 (2H, t, J ¼ 6.5 Hz, –OCH2), 1.28–1.85
(16H, m, –(CH2)8), 0.88 (3H, t, J ¼ 6.7 Hz, –CH3). 13C NMR (CDCl3):
d
14.09, 22.65, 25.87, 28.45, 29.24, 29.50, 29.68, 30.15, 31.86, 68.35,
116.98, 125.82, 138.53, 142.85, 160.78. IR (KBr) cmꢀ1: 1587 (C]C),
1622 (C]N), 1251, 1026 (C–O–C), 1168 (N–N). MS m/z: 277(M þ 1).
Anal. Calcd for C15H24N4O: C, 65.19; H, 8.75; N, 20.27. Found: C,
65.05; H, 8.76; N, 20.14.
3.4.14. 6-(3-Chlorophenoxy)-[1,2,4]triazolo[4,3-b]pyridazine (2n)
Yield: 58.4%; m.p.: 142–144 ꢂC. 1H NMR (CDCl3):
d 8.82 (1H, s,
triazolo-H), 8.14 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.04 (1H, d,
J ¼ 9.8 Hz, pyridazine-H), 7.13–7.45 (4H, m, –C6H4). 13C NMR
(CDCl3):
d 116.05, 119.62, 121.98, 122.90, 126.24, 126.66, 127.30,
3.4.8. 6-(2-Tolyloxy)-[1,2,4]triazolo[4,3-b]pyridazine (2h)
130.65, 138.72, 142.83, 160.57. IR (KBr) cmꢀ1: 1588 (C]C), 1621
(C]N), 1250, 1026 (C–O–C), 1169 (N–N). MS m/z: 247 (M þ 1). Anal.
Calcd for C11H7ClN4O: C, 53.56; H, 2.86; N, 22.71. Found: C, 53.41; H,
2.70; N, 22.62.
Yield: 68.3%; m.p.: 108–110 ꢂC. 1H NMR (CDCl3):
d 8.76 (1H, s,
triazolo-H), 8.11 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.07 (1H, d,
J ¼ 9.8 Hz, pyridazine-H), 7.11–7.33 (4H, m, –C6H4). 13C NMR
(CDCl3): d 16.18, 101.21, 115.99, 121.48, 125.61, 126.56, 127.07, 127.36,
131.64, 138.71, 142.92, 167.77. IR (KBr) cmꢀ1: 1590 (C]C), 1620
(C]N), 1251, 1024 (C–O–C), 1174 (N–N). MS m/z: 227 (M þ 1). Anal.
Calcd for C12H10N4O: C, 63.71; H, 4.46; N, 24.76. Found: C, 63.65; H,
4.37; N, 24.67.
3.4.15. 6-(4-Fluorophenoxy)-[1,2,4]triazolo[4,3-b]pyridazine (2o)
Yield: 58%; m.p.: 201–203 ꢂC. 1H NMR (CDCl3):
d 8.79 (1H, s,
triazolo-H), 8.13 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.04 (1H, d,
J ¼ 9.8 Hz, pyridazine-H), 7.13–7.20 (4H, m, –C6H4).13C NMR (CDCl3):
d
116.14,116.46,116.78,122.75,122.86,127.14,138.70,142.86,162.08.
3.4.9. 6-(3-Tolyloxy)-[1,2,4]triazolo[4,3-b]pyridazine (2i)
IR (KBr) cmꢀ1: 1589 (C]C), 1620 (C]N), 1252, 1026 (C–O–C), 1170
(N–N). MS m/z: 231 (M þ 1). Anal. Calcd for C11H7FN4O: C, 57.39; H,
3.07; N, 24.34. Found: C, 57.25; H, 2.91; N, 24.17.
Yield: 71%; m.p.: 131–133 ꢂC. 1H NMR (CDCl3):
d 8.81 (1H, s,
triazolo-H), 8.11 (1H, d, J ¼ 9.7 Hz, pyridazine-H), 7.03 (1H, d,
J ¼ 9.7 Hz, pyridazine-H), 7.14–7.39 (4H, m, –C6H4). 13C NMR
(CDCl3):
d
21.38, 116.38, 118.11, 121.71, 126.91, 127.12, 128.48, 129.60,
3.4.16. 6-(4-Chlorophenoxy)-[1,2,4]triazolo[4,3-b]pyridazine (2p)
138.75, 142.89, 153.75, 160.45. IR (KBr) cmꢀ1: 1585 (C]C), 1621
(C]N), 1254, 1028 (C–O–C), 1169 (N–N). MS m/z: 227 (M þ 1). Anal.
Calcd for C12H10N4O: C, 63.71; H, 4.46; N, 24.76. Found: C, 63.60; H,
4.31; N, 24.59.
Yield: 61%; m.p.: 189–191 ꢂC. 1H NMR (CDCl3):
d
8.80 (1H, s, tri-
azolo-H), 8.13 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.04 (1H, d, J ¼ 9.8 Hz,
pyridazine-H), 7.17–7.46 (4H, m, –C6H4). 13C NMR (CDCl3):
116.13,
d
122.69, 126.24, 127.23, 130.00, 138.68, 142.57, 160.73. 165.14. IR
(KBr) cmꢀ1: 1587 (C]C), 1622 (C]N), 1254, 1029 (C–O–C), 1173 (N–
N). MS m/z: 247(M þ 1). Anal. Calcd for C11H7ClN4O: C, 53.56; H,
2.86; N, 22.71. Found: C, 53.49; H, 2.76; N, 22.69.
3.4.10. 6-(4-Tolyloxy)-[1,2,4]triazolo[4,3-b]pyridazine (2j)
Yield: 73.6%; m.p.: 127–129 ꢂC. 1H NMR (CDCl3):
d 8.79 (1H, s,
triazolo-H), 8.09 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.02 (1H, d,
J ¼ 9.8 Hz, pyridazine-H), 7.08–7.24 (4H, m, –C6H4). 13C NMR
3.4.17. 6-(4-bromophenoxy)-[1,2,4]triazolo[4,3-b]pyridazine (2q)
(CDCl3):
d
20.95, 116.40, 120.90, 122.89, 126.25, 126.88, 128.17,
Yield: 72.1%; m.p.: 190–193 ꢂC. 1H NMR (CDCl3):
d 8.79 (1H, s,
130.40, 138.75, 142.56, 149.86, 161.13. IR (KBr) cmꢀ1: 1588 (C]C),
1623 (C]N), 1254, 1026 (C–O–C), 1172 (N–N). MS m/z: 227(M þ 1).
Anal. Calcd for C12H10N4O: C, 63.71; H, 4.46; N, 24.76. Found: C,
63.63; H, 4.39; N, 24.69.
triazolo-H), 8.13 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.04 (1H, d,
J ¼ 9.8 Hz, pyridazine-H), 7.11–7.60 (4H, m, –C6H4). 13C NMR
(CDCl3):
d116.13, 119.44, 122.90, 127.24, 132.25, 132.99, 138.68,
142.84, 160.66. IR (KBr) cmꢀ1: 1588 (C]C), 1620 (C]N), 1251, 1028
(C–O–C), 1173 (N–N). MS m/z: 291(M þ 1). Anal. Calcd for
C11H7BrN4O: C, 45.39; H, 2.42; N, 19.25. Found: C, 45.21; H, 2.32; N,
19.04.
3.4.11. 6-(2-Methoxyphenoxy)-[1,2,4]triazolo[4,3-b]pyridazine (2k)
Yield: 69.5%; oil. H NMR (CDCl3):
d 8.77 (1H, s, triazolo-H),
8.09 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.07 (1H, d, J ¼ 9.8 Hz,
pyridazine-H), 7.04–7.32 (4H, m, –C6H4). 13C NMR (CDCl3):
3.4.18. 6-(2,4-Dichlorophenoxy)-[1,2,4]triazolo[4,3-b]pyridazine
d
55.82, 112.77, 116.07, 121.04, 122.59, 126.62, 127.41, 138.65,
(2r)
142.79, 145.13, 160.70, 165.54. IR (KBr) cmꢀ1: 1587(C]C), 1621
(C]N), 1252, 1026 (C–O–C), 1170 (N–N). MS m/z: 243 (M þ 1).
Anal. Calcd for C12H10N4O2: C, 59.50; H, 4.16; N, 23.13. Found: C,
59.45; H, 4.04; N, 23.01.
Yield: 59%; m.p.: 192–194 ꢂC. 1H NMR (CDCl3):
d 8.78 (1H, s,
triazolo-H), 8.16 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.11 (1H, d,
J ¼ 9.8 Hz, pyridazine-H), 7.22–7.54 (3H, m, –C6H3). 13C NMR
(CDCl3):
d 115.50, 124.39, 127.51, 128.42, 130.65, 131.12, 131.54,
132.58, 138.61, 143.15, 160.59. IR (KBr) cmꢀ1: 1587 (C]C), 1624
(C]N), 1251, 1028 (C–O–C), 1168 (N–N). MS m/z: 281 (M þ 1). Anal.
Calcd for C11H6Cl2N4O: C, 47.00; H, 2.15; N, 19.93. Found: C, 47.12; H,
2.19; N, 20.14.
3.4.12. 6-(4-Methoxyphenoxy)-[1,2,4]triazolo[4,3-b]pyridazine (2l)
Yield: 72%; m.p.: 186–188 ꢂC. 1H NMR (CDCl3):
d
8.79 (1H, s,
triazolo-H), 8.10 (1H, d, J ¼ 9.8 Hz, pyridazine-H), 7.02 (1H, d,