Page 7 of 13
The Journal of Organic Chemistry
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N-(2-(1,4-Dioxo-3,4-dihydrophthalazin-2(1H)-yl)-4,5-
124.9, 124.4, 124.0, 121.7, 118.7, 20.8; IR (KBr) υ 3137, 3108, 3064,
1654, 1640, 1610, 1574, 1550, 1509, 1489, 1320, 1280, 746 cm-1;
HRMS (ESI) m/z: [M+H]+ Calcd for C22H16Cl2N3O3 440.0563;
Found 440.0563.
dimethylphenyl)-3-methylbenzamide (3h). 74.3 mg (93%);
eluent (n-hexanes/EtOAc = 2:1); pale yellow solid; mp =
218.3–220.4 oC; 1HNMR (400 MHz, CDCl3) δ 9.25 (s, 1H), 8.61–
8.47 (m, 1H), 7.86–7.76 (m, 3H), 7.69 (brs, 2H), 7.64 (brs, 1H),
7.27 (brs, 2H), 6.71 (s, 1H), 2.32 (s, 3H), 2.11 (s, 3H), 1.40 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 165.9, 159.4, 152.5, 138.5,
137.1, 134.3, 134.1, 133.5, 132.7, 132.5, 132.1, 129.6, 128.9, 128.6,
128.1, 127.4, 127.3, 126.5, 125.1, 124.6, 124.4, 21.4, 19.5, 18.5; IR
(KBr) υ 3338, 3055, 2941, 2832, 1646, 1587, 1515, 1474, 1453, 1403,
1362, 1326, 1267, 1195, 1091, 1037, 1026, 884 cm-1; HRMS (EI)
m/z: [M]+ Calcd for C24H21N3O3 399.1578; Found 399.1580.
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3-Methyl-N-(2-(5,6,7,8-tetrafluoro-1,4-dioxo-3,4-
dihydrophthalazin-2(1H)-yl)phenyl)benzamide (3n). 85.2 mg
(96%); eluent (CH2Cl2/MeOH = 20:1); pale yellow solid; mp =
259.0–260.0 oC; 1H NMR (400 MHz, DMSO-d6) δ 12.30 (s, 1H),
9.77 (s, 1H), 8.09 (dd, J = 8.2, 1.4 Hz, 1H), 7.55 (s, 1H), 7.54–
7.52 (m, 1H), 7.50 (dd, J = 8.0, 1.5 Hz, 1H), 7.46 (td, J = 7.8, 1.6
Hz, 1H), 7.33 (d, J = 1.2 Hz, 1H), 7.32 (d, J = 2.8 Hz, 1H), 7.29
(td, J = 7.6, 1.4 Hz, 1H), 2.31 (s, 3H); 13C{1H} NMR (100 MHz,
DMSO-d6) δ 166.0, 153.1, 150.7, 147.3, 144.9, 143.4, 141.9, 137.4,
135.2, 134.3, 132.4, 132.0, 128.6 (d, JC-F = 2.3 Hz), 128.5, 128.2,
124.9, 124.5, 124.0, 119.2, 115.4, 111.5, 20.80; 19F NMR (470 MHz,
DMSO-d6) δ −138.2 (s, 1F), −140.2 (s, 1F), −150.0 (t, J = 18.9 Hz,
1F), −147.3 (td, J = 23.1, 7.9 Hz, 1F); IR (KBr) υ 3136, 3106, 3064,
1655, 1638, 1600, 1570, 1542, 1516, 1474, 1367, 1321, 1262, 1166,
1099, 1080, 956, 850, 773 cm-1; HRMS (ESI) m/z: [M+H]+
Calcd for C22H14F4N3O3 444.0966; Found 444.0966.
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N-(2-(3,6-Dioxo-3,6-dihydropyridazin-1(2H)-yl)phenyl)-3-
methylbenzamide (3j). 63.0 mg (98%); eluent (CH2Cl2/MeOH
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= 30:1); brown solid; mp = 211.6–213.5 C; H NMR (400 MHz,
DMSO-d6) δ 11.42 (brs, 1H), 9.59 (s, 1H), 8.31 (s, 1H), 7.88 (d, J
= 8.0 Hz, 1H), 7.59 (brs, 1H), 7.56 (dd, J = 6.1, 2.6 Hz, 1H), 7.45
(t, J = 8.2 Hz, 2H), 7.37–7.36 (m, 1H), 7.31 (t, J = 7.6 Hz, 1H),
7.18 (d, J = 9.8 Hz, 1H), 7.06 (d, J = 9.8 Hz, 1H), 2.36 (s, 3H);
13C{1H} NMR (100 MHz, DMSO-d6) δ 165.1, 158.1, 153.4, 137.7,
134.6, 134.4, 133.6, 133.4, 132.2, 128.4, 128.3, 128.1, 128.0, 127.9,
125.0, 124.9, 124.5, 20.9; IR (KBr) υ 3389, 3055, 2942, 2831, 1669,
1578, 1509, 1447, 1267, 1108, 1027, 837 cm-1; HRMS (EI) m/z:
[M]+ Calcd for C18H15N3O3 321.1108; Found 321.1103.
4-Chloro-N-(2-(1,4-dioxo-3,4-dihydrophthalazin-2(1H)-
yl)phenyl)benzamide (4b). 64.2 mg (82%); eluent (n-
hexanes/EtOAc = 1.5:1); pale yellow solid; mp = 234.7–236.8
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oC; H NMR (500 MHz, DMSO-d6) δ 11.86 (brs, 1H), 9.85 (s,
N-(2-(4,5-Dimethyl-3,6-dioxo-3,6-dihydropyridazin-1(2H)-
yl)phenyl)-3-methylbenzamide (3k). 69.2 mg (99%); eluent (n-
1H), 8.29 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 6.9 Hz, 2H), 7.97–7.93
(m, 1H), 7.92–7.88 (m, 1H), 7.75 (d, J = 8.5 Hz, 2H), 7.53 (dd, J
= 8.4, 2.2 Hz, 1H), 7.49 (d, J = 8.5 Hz, 2H), 7.47–7.42 (m, 1H),
7.34–7.28 (m, 1H); 13C{1H} NMR (125 MHz, DMSO-d6) δ 166.8,
164.6, 157.8, 136.2, 133.9, 133.8, 133.4, 132.3, 129.6, 129.6, 129.4,
128.7, 128.3, 128.1, 126.7, 124.8, 124.6, 124.2, 124.1; IR (KBr) υ
3340, 3065, 2910, 2890, 1642, 1583, 1546, 1492, 1453, 1322, 1293,
1235, 1092, 940, 842 cm-1; HRMS (EI) m/z: [M]+ Calcd for
C21H14ClN3O3 391.0719; Found 391.0724.
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hexanes/EtOAc = 2:1); yellow solid; mp = 234.0–235.0 C; H
NMR (400 MHz, DMSO-d6) δ 11.46 (s, 1H), 9.55 (s, 1H), 7.94
(ddd, J = 8.2, 4.8, 1.4 Hz, 1H), 7.55 (d, J = 2.8 Hz, 2H), 7.49 (dd,
J = 7.9, 1.5 Hz, 1H), 7.45 (dd, J = 7.7, 1.7 Hz, 1H), 7.39 (s, 1H),
7.38 (d, J = 3.2 Hz, 1H), 7.31 (td, J = 7.6, 1.5 Hz, 1H), 2.36 (s, 3H),
2.15 (s, 3H), 2.10 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d6) δ
164.8, 158.9, 153.1, 138.2, 137.8, 134.5, 133.3, 133.2, 132.3, 128.5,
128.2, 128.1, 127.8, 124.9, 124.7, 124.6, 124.5, 21.0, 13.1, 12.9; IR
(KBr) υ 3182, 3157, 1719, 1677, 1656, 1596, 1583, 1508, 1445, 1382,
1303, 1266, 1102, 1075, 931, 848, 806, 761 cm-1; HRMS (ESI) m/z:
[M+H]+ Calcd for C20H20N3O3 350.1499; Found 350.1499.
4-Bromo-N-(2-(1,4-dioxo-3,4-dihydrophthalazin-2(1H)-
yl)phenyl)benzamide (4c). 61.9 mg (71%); eluent (n-
hexanes/EtOAc = 1.5:1); pale yellow solid; mp = 160.6–162.7
oC; 1H NMR (700 MHz, DMSO-d6) δ 11.82 (s, 1H), 9.82 (s, 1H),
8.33–8.27 (m, 1H), 7.99 (t, J = 7.0 Hz, 2H), 7.95 (td, J = 7.6, 1.3
Hz, 1H), 7.91 (td, J = 7.8, 1.3 Hz, 1H), 7.67 (d, J = 8.6 Hz, 2H),
7.62 (d, J = 8.6 Hz, 2H), 7.55–7.50 (m, 1H), 7.48–7.42 (m, 1H),
7.31 (td, J = 7.8, 1.3 Hz, 1H); 13C{1H} NMR (175 MHz, DMSO-d6)
δ 164.7, 157.7, 151.3, 134.1, 133.8, 133.4, 132.3, 131.2, 129.7, 129.6,
129.5, 128.6, 128.0, 126.7, 126.6, 125.1, 124.8, 124.5, 124.1; IR (KBr)
υ 3380, 3077, 2921, 2853, 1641, 1586, 1543, 1490, 1454, 1321, 1267,
1010, 841 cm-1; HRMS (EI) m/z: [M]+ Calcd for C21H14BrN3O3
435.0214; Found 435.0219.
N-(2-(1,4-Dioxo-3,4-dihydrobenzo[g]phthalazin-2(1H)-
yl)phenyl)-3-methylbenzamide (3l). 68.2 mg (81%); eluent
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(CH2Cl2/MeOH = 40:1); yellow solid; mp = 249.8–251.6 C; H
NMR (500 MHz, CDCl3) δ 8.93 (s, 1H), 8.58 (s, 1H), 8.04–8.00
(m, 2H), 7.88 (d, J = 8.1 Hz, 1H), 7.66–7.59 (m, 2H), 7.58–7.50
(m, 3H), 7.40 (td, J = 7.9, 1.5 Hz, 1H), 7.30–7.23 (m, 1H), 7.21–
7.13 (m, 2H), 2.21 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3/CD3OD 10:1 v/v) δ 166.4, 159.1, 153.8, 138.5, 135.1, 134.6,
134.3, 133.8, 132.9, 132.8, 129.4, 129.2, 129.1, 128.9, 128.8, 128.7,
128.5, 127.9, 127.8, 126.2, 126.1, 125.9, 124.7, 124.2, 121.7, 21.1; IR
(KBr) υ 3366, 3055, 2926, 2853, 1645, 1615, 1584, 1511, 1476, 1446,
1299, 1268, 1198, 1169, 1120, 1075, 1027, 961, 916, 863 cm-1;
HRMS (EI) m/z: [M]+ Calcd for C26H19N3O3 421.1421; Found
421.1419.
N-(2-(1,4-Dioxo-3,4-dihydrophthalazin-2(1H)-yl)phenyl)-4-
(trifluoromethyl)benzamide (4d). 83.3 mg (98%); eluent (n-
hexanes/EtOAc = 1.5:1); pale yellow solid; mp = 264.2–266.4
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oC; H NMR (500 MHz, DMSO-d6) δ 11.86 (brs, 1H), 10.04 (s,
1H), 8.29 (d, J = 7.0 Hz, 1H), 8.05–7.97 (m, 2H), 7.95 (dd, J =
7.2, 1.3 Hz, 1H), 7.94–7.89 (m, 3H), 7.79 (d, J = 8.3 Hz, 2H),
7.54 (dd, J = 7.9, 1.4 Hz, 1H), 7.49–7.42 (m, 1H), 7.32 (td, J = 7.7,
1.4 Hz, 1H); 13C{1H} NMR (175 MHz, DMSO-d6) δ 164.6, 164.5,
157.7, 139.0, 133.7, 133.6, 133.4, 132.3, 131.1 (q, JC-F = 31.8 Hz),
129.6, 128.7, 128.5, 128.1, 126.6, 125.1 (q, JC-F = 3.7 Hz), 125.0,
124.5, 124.4, 123.8 (q, JC-F = 270.6 Hz), 123.0; IR (KBr) υ 3400,
3125, 2932, 2805, 1644, 1618, 1582, 1544, 1497, 1455, 1322, 1171,
1106, 1066, 1016, 905, 854 cm-1; HRMS (EI) m/z: [M]+ Calcd for
C22H14F3N3O3 425.0982; Found 425.0981.
N-(2-(6,7-Dichloro-1,4-dioxo-3,4-dihydrophthalazin-2(1H)-
yl)phenyl)-3-methylbenzamide (3m). 81.0 mg (92%); eluent
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(CH2Cl2/MeOH = 20:1); white solid; mp = 254.0–256.0 C; H
NMR (400 MHz, DMSO-d6) δ 12.27 (s, 1H), 9.77 (s, 1H), 8.41 (s,
1H), 8.17 (s, 1H), 8.08 (d, J = 7.8 Hz, 1H), 7.53–7.51 (m, 1H), 7.51
(s, 1H), 7.51–7.49 (m, 1H), 7.46 (td, J = 7.6, 1.6 Hz, 1H), 7.33–
7.30 (m, 2H), 7.28 (t, J = 7.2 Hz, 1H), 2.28 (s, 3H); 13C{1H} NMR
(100 MHz, DMSO-d6) δ 165.8, 161.6, 149.9, 137.4, 136.8, 136.6,
135.4, 135.1, 134.1, 132.0, 130.9, 129.7, 128.5, 128.3, 128.2, 126.3,
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