D. Mantu et al. / European Journal of Medicinal Chemistry 45 (2010) 5164e5168
5167
00
4.1.2.1. 2-Allyl-6-(4-chlorophenyl)pyridazin-3(2H)-one (2a). White
crystals; mp 86e88 ꢁC; Anal. C13H11ClN2O (C, H, N); IR (KBr):
cmꢂ1: 1656 (COcet); 1H NMR (400 MHz, CDCl3): dppm: 4.85e4.83
7.15e7.13 (d, J ¼ 9.6 Hz, 1H, H4), 7.58e7.56 (d, J ¼ 8.4 Hz, 2H, H2 ),
00
y/
7.93e7.90 (d, J ¼ 8.4 Hz, 2H, H3 ), 8.15e8.12 (d, J ¼ 9.6 Hz, 1H, H5).
13C NMR (400 MHz, DMSO-d6): dppm: 52.27 (C4 ), 53.46 (C1 ), 127.63
0
0
0
0
0
0
0
0
0
0
(false d, J ¼ 6.0 Hz, 2H, H1 ), 5.32e5.26 (t, J ¼ 10.0, 1.6 Hz, 2H, H3 ),
(C3 ), 128.94 (C2 ), 129.75 (C4), 131.43 (C5), 132.79 (C3), 134.36 (C4 ),
0
00
0
6.10e6.01 (m, J ¼ 10.0, 6.0, 1.6 Hz, 1H, H2 ), 7.04e7.02 (d, J ¼ 9.6 Hz,
142.86 (C1 ), 158.73 (C6), 167.97 (C2 ).
00
1H, H4), 7.43e7.41 (d, J ¼ 8.4 Hz, 2H, H2 ), 7.68e7.63 (d, J ¼ 9.6 Hz,
1H, H5), 7.73e7.71 (d, J ¼ 8.4 Hz, 2H, H3 ). 13C NMR (400 MHz,
4.1.2.8. Methyl 2-(3-(4-bromophenyl)-6-oxopyridazin-1(6H)-yl)ace-
00
CDCl3): dppm: 54.59 (C1 ), 118.73 (C3 ), 127.14 (C3 ), 129.14 (C2 ),
tate (4b). White crystals; mp 142e144 ꢁC; Anal. C13H11BrN2O3 (C,
0
0
00
00
H, N); IR (KBr): y
/cmꢂ1: 1747 (COest), 1666 (COcet); 1H NMR
0
00
129.76 (C5), 130.28 (C4), 131.71 (C2 ), 133.14 (C3), 135.59 (C1 ), 143.42
00
0
0
(C4 ), 159.42 (C6).
(400 MHz, DMSO-d6): dppm: 3.70 (s, 3H, H4 ), 4.97 (s, 2H, H1 ),
00
7.15e7.13 (d, J ¼ 9.6 Hz, 1H, H4), 7.58e7.56 (d, J ¼ 8.4 Hz, 2H, H2 ),
00
4.1.2.2. 2-Allyl-6-(4-bromophenyl)pyridazin-3(2H)-one (2b). White
7.93e7.90 (d, J ¼ 8.4 Hz, 2H, H3 ), 8.15e8.12 (d, J ¼ 9.6 Hz, 1H, H5).
crystals; mp 81e83 ꢁC; Anal. C13H11BrN2O (C, H, N); IR (KBr):
y/
13C NMR (400 MHz, DMSO-d6): dppm: 52.27 (C4 ), 53.46 (C1 ), 127.63
0
0
cmꢂ1: 1658 (COcet); 1H NMR (400 MHz, CDCl3): dppm: 4.85e4.83 (d,
00 00 00
(C3 ), 128.94 (C2 ), 129.75 (C4), 131.43 (C5), 132.79 (C3), 134.36 (C4 ),
0
0
0
0
0
J ¼ 6.0 Hz, 2H, H1 ), 5.32e5.26 (dt, J ¼ 10.0, 1.6 Hz, 2H, H3 ),
142.86 (C1 ), 158.73 (C6), 167.97 (C2 ).
0
6.11e6.01 (m, J ¼ 10.0, 6.0, 1.6 Hz, 1H, H2 ), 7.04e7.01 (d, J ¼ 9.6 Hz,
00
1H, H4), 7.59e7.57 (d, J ¼ 8.4 Hz, 2H, H2 ), 7.67e7.63 (dd, J ¼ 9.6,
4.1.2.9. Methyl
2-(6-oxo-3-p-tolylpyridazin-1(6H)-yl)acetate
8.4 Hz, 3H, H3 , H5,). 13C NMR (400 MHz, CDCl3): dppm: 54.51 (C1 ),
(4c). White crystals; mp 100e102 ꢁC; Anal. C14H14N2O3 (C, H, N); IR
00
0
(KBr): y
/cmꢂ1: 1743 (COest), 1670 (COcet); 1H NMR (400 MHz,
0
00
00
118.50 (C3 ), 127.32 (C3 ), 129.65 (C2 ), 129.78 (C5), 130.28 (C4),
131.97 (C2 ), 131.99 (C3), 139.58 (C4 ), 143.42 (C1 ), 159.56 (C6).
CDCl3): dppm: 2.39 (s, 3H, CH3 from 400 position), 3.79 (s, 3H, H4 ),
0
00
00
0
0
4.97 (s, 2H, H1 ), 7.05e7.02 (d, J ¼ 9.6 Hz, 1H, H4), 7.26e7.24 (d,
00
00
4.1.2.3. 2-Allyl-6-p-tolylpyridazin-3(2H)-one (2c). White crystals;
J ¼ 8.4 Hz, 2H, H3 ), 7.66e7.64 (d, J ¼ 8.4 Hz, 2H, H2 ), 7.71e7.69 (d,
mp 62e64 ꢁC; Anal. C14H14N2O (C, H, N); IR (KBr): /cmꢂ1: 1658
y
J ¼ 9.6 Hz, 1H, H5). 13C NMR (400 MHz, CDCl3): dppm: 21.30 (CH3
(COcet); 1H NMR (400 MHz, CDCl3): dppm: 2.39 (s, 3H, CH3 from 400
from 400 position), 52.58 (C4 ), 53.65 (C1 ), 125.99 (C2 ), 129.67 (C3 ),
0
0
00
00
0
00
00
position), 4.85e4.84 (dd, J ¼ 6.0 Hz, 2H, H1 ), 5.32e5.25 (dt, J ¼ 10.0,
130.11 (C4), 131.08 (C5), 131.66 (C1 ), 139.83 (C4 ), 145.14 (C3), 159.71
0
0
0
1.6 Hz, 2H, H3 ), 6.12e6.02 (m, J ¼ 10.0, 6.0, 1.6 Hz, 1H, H2 ),
(C6), 167.92 (C2 ).
00
7.02e6.99 (d, J ¼ 9.6 Hz, 1H, H4), 7.27e7.25 (d, J ¼ 8.4 Hz, 2H, H2 ),
7.68e7.64 (dd, J ¼ 9.6, 8.4 Hz, 3H, H5, H3 ). 13C NMR (400 MHz,
4.1.2.10. Ethyl 2-(3-(4-chlorophenyl)-6-oxopyridazin-1(6H)-yl)ace-
00
CDCl3): dppm: 21.29 (CH3 from 400 position), 54.51 (C1 ), 118.50 (C3 ),
tate (5a). White crystals; mp 164e166 ꢁC; Anal. C14H13ClN2O3 (C, H,
0
0
N); IR (KBr): y
/cmꢂ1: 1755 (COest), 1670 (COcet); 1H NMR (400 MHz,
00
00
0
125.80 (C3 ),129.65 (C2 ),130.09 (C5),130.14 (C4),131.97 (C2 ),131.99
00
00
0
(C3), 139.58 (C4 ), 144.61 (C1 ), 159.58 (C6).
DMSO-d6): dppm: 1.23e1.19 (t, J ¼ 7.2 Hz, 3H, H5 ), 4.19e4.14 (q,
0
0
J ¼ 7.2 Hz, 2H, H4 ), 4.95 (s, 2H, H1 ), 7.15e7.12 (d, J ¼ 10.0 Hz,1H, H4),
00
00
4.1.2.4. 6-(4-Chlorophenyl)-2-(prop-2-ynyl)pyridazin-3(2H)-one
7.58e7.56 (d, J ¼ 8.8 Hz, 2H, H2 ), 7.93e7.90 (d, J ¼ 8.8 Hz, 2H, H3 ),
(3a). Pink crystals; mp 123e125 ꢁC; Anal. C13H9ClN2O (C, H, N); IR
8.14e8.12 (d, J ¼ 10.0 Hz, 1H, H5). 13C NMR (400 MHz, DMSO-d6):
0 0 0 00 00
dppm: 13.96 (C5 ), 53.56 (C1 ), 61.14 (C4 ), 127.63 (C3 ), 128.95 (C2 ),
(KBr):
y
/cmꢂ1: 1661 (COcet); 1H NMR (400 MHz, CDCl3): dppm
:
0
0
00
00
2.37e2.35 (false t, 1H, H3 ), 4.99 (s, 2H, H1 ), 7.05e7.03 (d,
129.75 (C4), 131.41 (C5), 132.82 (C3),134.35 (C4 ), 142.82 (C1 ), 158.74
00
0
J ¼ 10.0 Hz, 1H, H4), 7.44e7.42 (d, J ¼ 8.4 Hz, 2H, H2 ), 7.67e7.65 (d,
(C6), 167.46 (C2 ).
J ¼ 10.0, Hz, 1H, H5), 7.75e7.73 (d, J ¼ 8.4 Hz, 2H, H3 ). 13C NMR
00
0
0
0
(400 MHz, CDCl3): dppm: 41.84 (C1 ), 73.14 (C3 ), 77.23 (C2 ), 127.23
4.1.2.11. Ethyl
2-(3-(4-bromophenyl)-6-oxopyridazin-1(6H)-yl)
00
00
00
(C3 ), 129.19 (C2 ), 130.32 (C4), 130.44 (C5), 132.83 (C3), 135.84 (C1 ),
acetate (5b). White crystals; mp 164e166 ꢁC; Anal. C14H13BrN2O3
143.79 (C4 ), 158.86 (C6).
(C, H, N); IR (KBr):
y
/cmꢂ1: 1753 (COest), 1670 (COcet); 1H NMR
00
0
(400 MHz, DMSO-d6): dppm: 1.23e1.20 (t, J ¼ 7.2 Hz, 3H, H5 ),
0
0
4.1.2.5. 6-(4-Bromophenyl)-2-(prop-2-ynyl)pyridazin-3(2H)-one
4.20e4.15 (q, J ¼ 7.2 Hz, 2H, H4 ), 4.95 (s, 2H, H1 ), 7.15e7.13 (d,
(3b). White crystals; mp 132e134 ꢁC; Anal. C13H9BrN2O (C, H, N);
J ¼ 10.0 Hz, 1H, H4), 7.72e7.70 (d, J ¼ 8.8 Hz, 2H, H2 ), 7.86e7.84 (d,
00
00
IR (KBr):
y
/cmꢂ1: 1665 (COcet); 1H NMR (400 MHz, CDCl3): dppm
:
J ¼ 8.8 Hz, 2H, H3 ), 8.14e8.12 (d, J ¼ 10.0 Hz, 1H, H5). 13C NMR
0
0
0 0 0
(400 MHz, DMSO-d6): dppm: 13.98 (C5 ), 53.58 (C1 ), 61.16 (C4 ),
2.36e2.35 (false t, 1H, H3 ), 4.98 (s, 2H, H1 ), 7.04e7.01 (d,
00
0
0
0
0
J ¼ 10.0 Hz, 1H, H4), 7.58e7.56 (d, J ¼ 8.8 Hz, 2H, H2 ), 7.67e7.63 (dd,
123.13 (C3), 127.89 (C3 ), 129.76 (C4), 131.37 (C5), 131.89 (C2 ), 133.19
J ¼ 10.0, 8.8 Hz, 3H, H3 , H5). 13C NMR (400 MHz, CDCl3):
d
¼ 41.81
(C4 ), 142.91 (C1 ), 158.76 (C6), 167.47 (C2 ).
00
00
00
0
0
0
0
00
(C1 ), 73.15 (C3 ), 77.18 (C2 ), 124.06 (C3), 127.43 (C3 ), 130.23 (C5),
00
00
00
130.38 (C4), 132.08 (C2 ), 133.21 (C4 ), 143.77 (C1 ), 158.80 (C6).
4.1.2.12. Ethyl 2-(6-oxo-3-p-tolylpyridazin-1(6H)-yl)acetate (5c).
White crystals; mp 134e135 ꢁC; Anal. C15H16N2O3 (C, H, N); IR (KBr):
4.1.2.6. 2-(Prop-2-ynyl)-6-p-tolylpyridazin-3(2H)-one (3c). White
y
/cmꢂ1: 1755 (COest), 1670 (COcet); 1H NMR (400 MHz, DMSO-d6):
crystals; mp 94e96 ꢁC; Anal. C14H12N2O (C, H, N); IR (KBr):
y
/cmꢂ1
:
dppm: 1.24e1.20 (t, J ¼ 7.2 Hz, 3H, H5 ), 2.36 (s, 3H, CH3 from 400
0
1665 (COcet); 1H NMR (400 MHz, CDCl3): dppm: 2.36e2.34 (false t,
position), 4.20e4.15 (q, J ¼ 7.2 Hz, 2H, H4 ), 4.94 (s, 2H, H1 ), 7.12e7.10
0
0
00
0
00
1H, H3 ), 2.40 (s, 3H, CH3 from 4 position), 5.00e4.99 (false d, 2H,
(d, J ¼ 10.0 Hz, 1H, H4), 7.32e7.30 (d, J ¼ 8.4 Hz, 2H, H2 ), 7.80e7.78
H1 ), 7.03e7.01 (d, J ¼ 9.6 Hz, 1H, H4), 7.27e7.25 (d, J ¼ 8.0 Hz, 2H,
(d, J ¼ 8.4 Hz, 2H, H3 ), 8.11e8.09 (d, J ¼ 10.0 Hz, 1H, H5). 13C NMR
0
00
H2 ), 7.70e7.66 (dd, J ¼ 9.6, 8.0 Hz, 3H, H5, H3 ). 13C NMR (400 MHz,
(400 MHz, DMSO-d6): dppm: 13.96 (C5 ), 20.78 (CH3 from 4 position),
00
00
00
0
CDCl3): dppm: 21.31 (CH3 from 400 position), 41.83 (C1 ), 72.95 (C3 ),
0
0
0 0 00 00
53.52 (C1 ), 61.10 (C4 ), 125.73 (C3 ), 129.48 (C2 ), 129.63 (C4), 131.20
0
00
00
00
00
0
77.49 (C2 ), 125.90 (C3 ), 129.69 (C2 ), 130.24 (C4), 130.73 (C5), 131.66
(C1 ), 131.48 (C5), 139.20 (C4 ), 143.87 (C3), 158.78 (C6), 167.54 (C2 ).
00
00
(C3), 139.84 (C4 ), 145.02 (C1 ), 159.05 (C6).
4.1.2.13. Ethyl 2-(3-(4-chlorophenyl)-6-oxopyridazin-1(6H)-yl)prop-
4.1.2.7. Methyl
2-(3-(4-chlorophenyl)-6-oxopyridazin-1(6H)-yl)
anoate (6a). White crystals; mp 68e70 ꢁC; Anal. C15H15ClN2O3 (C,
acetate (4a). White crystals; mp 127e129 ꢁC; Anal. C13H11ClN2O3
H, N); IR (KBr):
(400 MHz, DMSO-d6): dppm
y
/cmꢂ1: 1739 (COest), 1670 (COcet); 1H NMR
/cmꢂ1: 1747 (COest), 1666 (COcet); 1H NMR
:
1.16e1.13 (t, J ¼ 7.2 Hz, 3H, H5 ),
0
(C, H, N); IR (KBr):
(400 MHz, DMSO-d6): dppm: 3.70 (s, 3H, H4 ), 4.97 (s, 2H, H1 ),
y
0
0
0
0
1.63e1.62 (d, J ¼ 7.2 Hz, 3H, H1 a), 4.17e4.09 (m, J ¼ 7.2 Hz, 2H, H4 ),