10
Y. Yang et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
11.7. ESI-HRMS (m/z): Calcd for C18H20N5O2 [M+H]+ 338.1612.
Found 338.1611.
4.2.5.7. (E)-6-Methyl-4-(1-(6-(3-nitrophenoxy)pyridin-3-yl)ethyl-
ideneamino)-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIIh). This
compound was obtained as a white solid in 63% yield; mp = 171–
172 °C; 1H NMR (400 MHz, DMSO-d6): d 9.98 (s, 1H, NH), 8.60 (s,
1H, Py-H), 8.38 (d, J = 8.8 Hz, 1H, Py-H), 8.12 (d, J = 8.0 Hz, 1H, Ar-
H), 8.06 (t, J = 2.0 Hz, 1H, Ar-H), 7.69–7.77 (m, 2H, Ar-H), 7.25 (d,
J = 8.8 Hz, 1H, Py-H), 4.16 (s, 2H, CH2), 2.20 (s, 3H, CH3), 1.95 (s, 3H,
CH3); 13C NMR (100 MHz, DMSO-d6) d 166.6, 163.5, 153.8, 148.7,
148.6, 146.4, 145.4, 138.7, 131.0, 128.8, 128.4, 119.8, 116.5, 111.7,
50.9, 20.1, 17.1. ESI-HRMS (m/z): Calcd for C17H17N6O4 [M+H]+
369.1306. Found 369.1311.
4.2.5.2. (E)-6-Methyl-4-(2-methyl-1-(6-phenoxypyridin-3-yl)propyl-
ideneamino)-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIIc).
This
compound was obtained as a white solid in 42% yield; mp = 40–
42 °C; 1H NMR (400 MHz, CDCl3): d 7.94 (s, 1H, NH), 7.65 (d,
J = 8.4 Hz, 1H, Py-H), 7.46 (s, 1H, Py-H), 7.41 (t, J = 7.6 Hz, 2H, Ar-
H), 7.22 (t, J = 7.2 Hz, 1H, Ar-H), 7.16 (d, J = 7.6 Hz, 2H, Ar-H), 6.88
(d, J = 8.4 Hz, 1H, Py-H), 3.97 (s, 2H, CH2), 2.89–2.99 (m, 1H, CH
(CH3)2), 1.89 (s, 3H, CH3), 1.19 (d, J = 6.8 Hz, 6H, CH(CH3)2); 13C
NMR (100 MHz, CDCl3) d 180.4, 163.8, 153.7, 148.4, 144.6, 144.4,
138.5, 129.9, 127.2, 125.2, 121.6, 110.9, 51.5, 37.2, 20.5, 20.1. ESI-
4.2.5.8. (E)-4-(1-(6-(3-Aminophenoxy)pyridin-3-yl)ethylideneamino)-
HRMS (m/z): Calcd for
C
19H22N5O2 [M+H]+ 352.1768. Found
6-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one
(IIIi).
This
352.1772.
compound was obtained as a white solid in 27% yield; mp = 187–
188 °C; 1H NMR (400 MHz, DMSO-d6): d 9.97 (s, 1H, NH), 8.60 (s,
1H, Py-H), 8.27 (d, J = 8.8 Hz, 1H, Py-H), 7.04 (t, J = 7.2 Hz, 1H, Ar-
H), 6.96 (d, J = 8.8 Hz, 1H, Py-H), 6.42 (d, J = 7.2 Hz, 1H, Ar-H),
6.29 (s, 1H, Ar-H), 6.24 (d, J = 7.2 Hz, 1H, Ar-H), 5.27 (s, 2H, NH2),
4.15 (s, 2H, CH2), 2.19 (s, 3H, CH3), 1.94 (s, 3H, CH3); 13C NMR
(100 MHz, DMSO-d6) d 166.6, 164.5, 154.4, 150.2, 148.6, 146.6,
145.2, 138.0, 129.7, 127.5, 110.6, 110.3, 107.6, 105.9, 50.7, 19.9,
16.8. ESI-HRMS (m/z): Calcd for C17H19N6O2 [M+H]+ 339.1564.
Found 339.1569.
4.2.5.3.
(Z)-6-Methyl-4-(2,2,2-trifluoro-1-(6-phenoxypyridin-3-yl)-
This
ethylideneamino)-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIId).
compound was obtained as a white solid in 41% yield; mp = 150–151 °C;
1H NMR (400 MHz, CDCl3): d 8.16 (s, 1H, NH), 8.13 (s, 1H, Py-H),7.82 (d,
J = 8.0 Hz, 1H, Py-H), 7.45 (t, J = 7.6 Hz, 2H, Ar-H), 7.28 (d, J = 7.2 Hz, 1H,
Ar-H), 7.19 (d, J = 8.0 Hz, 2H, Ar-H), 7.00 (d, J = 8.0 Hz, 1H, Py-H), 4.19 (s,
2H, CH2), 2.00 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) d 164.5, 153.2 (q,
J = 33 Hz), 153.1, 146.8, 146.2, 146.0, 139.1, 129.8, 125.5, 121.6, 120.1 (q,
J = 257 Hz), 111.5, 52.3, 20.5. ESI-HRMS (m/z): Calcd for C17H15F3N5O2 [M
+H]+ 378.1172. Found 378.1181.
4.2.5.9. (E)-4-(1-(6-(4-Ethylphenoxy)pyridin-3-yl)ethylideneamino)-
6-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one
(IIIj).
This
compound was obtained as a white solid in 59% yield; mp = 131–
132 °C; 1H NMR (400 MHz, DMSO-d6): d 9.96 (s, 1H, NH), 8.56 (s,
1H, Py-H), 8.29 (d, J = 8.8 Hz, 1H, Py-H), 7.27 (d, J = 7.2 Hz, 2H,
Ar-H), 7.09–7.04 (m, 3H, Ar-H, Py-H), 4.15 (s, 2H, CH2), 2.63 (q,
J = 6.8 Hz, 2H, CH2CH3), 2.18 (s, 3H, CH3), 1.94 (s, 3H, CH3), 1.21
(t, J = 7.6 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-d6) d 166.8,
164.6, 151.3, 148.8, 146.6, 145.4, 140.4, 138.3, 129.0, 127.8,
121.2, 110.9, 50.9, 27.6, 20.1, 17.0, 15.7. ESI-HRMS (m/z): Calcd
for C19H22N5O2 [M+H]+ 352.1768. Found 352.1772.
4.2.5.4. (E)-6-Methyl-4-(1-(6-(o-tolyloxy)pyridin-3-yl)ethylide-
neamino)-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIIe).
This
compound was obtained as a white solid in 56% yield; mp = 166–
167 °C; 1H NMR (400 MHz, DMSO-d6) d 9.97 (s, 1H, NH), 8.55 (s,
1H, Py-H), 8.31 (d, J = 8.8 Hz, 1H, Py-H), 7.34 (d, J = 7.6 Hz, 1H,
Ar-H), 7.27 (t, J = 7.6 Hz, 1H, Ar-H), 7.19 (t, J = 7.6 Hz, 1H, Ar-H),
7.13–7.07 (m, 2H, Py-H, Ar-H), 4.15 (s, 2H, CH2), 2.19 (s, 3H,
CH3), 2.09 (s, 3H, CH3), 1.95 (s, 3H, CH3); 13C NMR (100 MHz,
DMSO-d6) d 167.3, 164.8, 152.1, 149.3, 147.2, 145.9, 138.8, 131.7,
130.7, 128.1, 127.8, 125.8, 122.5, 110.8, 51.4, 20.6, 17.4, 16.4. ESI-
HRMS (m/z): Calcd for
C
18H20N5O2 [M+H]+ 338.1612. Found
4.2.5.10. (E)-4-(1-(6-(4-Isopropylphenoxy)pyridin-3-yl)ethylide-
neamino)-6-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIIk).
This
338.1616.
compound was obtained as a white solid in 53% yield; mp = 128–
129 °C; 1H NMR (400 MHz, DMSO-d6): d 9.96 (s, 1H, NH), 8.57 (s,
1H, Py-H), 8.29 (d, J = 8.8 Hz, 1H, Py-H), 7.30 (d, J = 8.4 Hz, 2H, Ar-H),
7.10–7.04 (m, 3H, Ar-H, Py-H), 4.15 (s, 2H, CH2), 2.89–2.96 (m, 1H,
CH(CH3)2), 2.18 (s, 3H, CH3), 1.94 (s, 3H, CH3), 1.22 (d, J = 6.8 Hz, 6H,
CH(CH3)2); 13C NMR (100 MHz, DMSO-d6) d 166.8, 164.6, 151.4, 148.8,
146.6, 145.4, 145.0, 138.3, 127.8, 127.5, 121.2, 110.9, 50.9, 32.9, 24.0,
20.1, 17.0. ESI-HRMS (m/z): Calcd for C20H24N5O2 [M+H]+ 366.1925.
Found 366.1930.
4.2.5.5. (E)-4-(1-(6-(2-Ethoxyphenoxy)pyridin-3-yl)ethylideneamino)-
6-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIIf). This
compound was obtained as yellow solid in 80% yield;
a
mp = 167–168 °C; 1H NMR (400 MHz, DMSO-d6): d 9.96 (s, 1H,
NH), 8.52 (s, 1H, Py-H), 8.27 (d, J = 8.8 Hz, 1H, Py-H), 7.12–7.23
(m, 3H, Ar-H), 6.96–7.04 (m, 2H, Py-H, Ar-H), 4.15 (s, 2H, CH2),
3.96 (q, J = 6.8 Hz, 2H, CH2CH3), 2.18 (s, 3H, CH3), 1.93 (s, 3H,
CH3), 1.05 (t, J = 6.8 Hz, 3H, CH2CH3); 13C NMR (100 MHz, DMSO-
d6) d 166.9, 164.5, 150.6, 148.8, 146.4, 145.3, 142.1, 137.9, 127.5,
126.2, 122.9, 120.9, 114.3, 110.0, 63.7, 50.9, 20.1, 16.9, 14.4. ESI-
4.2.5.11. (E)-4-(1-(6-(4-tert-Butylphenoxy)pyridin-3-yl)ethylide-
neamino)-6-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIIl).
This
HRMS (m/z): Calcd for
C
19H22N5O3 [M+H]+ 368.1717. Found
compound was obtained as a white solid in 86% yield; mp = 183–
184 °C; 1H NMR (400 MHz, DMSO-d6): d 9.97 (s, 1H, NH), 8.57 (s,
1H, Py-H), 8.30 (d, J = 8.8 Hz, 1H, Py-H), 7.45 (d, J = 8.8 Hz, 2H, Ar-H),
7.11–7.04 (m, 3H, Ar-H, Py-H), 4.15 (s, 2H, CH2), 2.19 (s, 3H, CH3),
1.94 (s, 3H, CH3), 1.31 (s, 9H, C(CH3)3); 13C NMR (100 MHz, DMSO-d6)
d 166.8, 164.6, 151.1, 148.8, 147.2, 146.6, 145.4, 138.3, 127.8, 126.5,
120.8, 110.9, 50.9, 34.2, 31.3, 20.1, 17.0. ESI-HRMS (m/z): Calcd for
C21H26N5O2 [M+H]+ 380.2081. Found 380.2089.
368.1722.
4.2.5.6. (E)-4-(1-(6-(2-tert-Butylphenoxy)pyridin-3-yl)ethylidene-
amino)-6-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIIg). This
compound was obtained as a white solid in 69% yield; mp = 122–
123 °C; 1H NMR (400 MHz, DMSO-d6): d 9.97 (s, 1H, NH), 8.59 (s,
1H, Py-H), 8.30 (d, J = 8.8 Hz, 1H, Py-H), 7.43 (d, J = 7.6 Hz, 1H, Ar-
H), 7.25 (t, J = 6.8 Hz, 1H, Ar-H), 7.18 (t, J = 7.6 Hz, 1H, Ar-H), 7.07
(d, J = 8.8 Hz, 1H, Py-H), 6.99 (d, J = 7.6 Hz, 1H, Ar-H), 4.15 (s, 2H,
CH2), 2.19 (s, 3H, CH3), 1.94 (s, 3H, CH3), 1.31 (s, 9H, CH3); 13C
4.2.5.12. (E)-4-(1-(6-(4-Bromophenoxy)pyridin-3-yl)ethylideneamino)-
6-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (IIIm).
This com-
NMR (100 MHz, DMSO-d6)
d 166.9, 164.6, 152.1, 148.8, 146.8,
pound was obtained as a white solid in 50% yield; mp = 204–205 °C;
1H NMR (400 MHz, DMSO-d6): d 9.98 (s, 1H, NH), 8.58 (s, 1H, Py-H),
8.32 (d, J = 8.8 Hz, 1H, Py-H), 7.62 (d, J = 8.8 Hz, 2H, Ar-H), 7.19–7.13
(m, 3H, Ar-H, Py-H), 4.15 (s, 2H, CH2), 2.19 (s, 3H, CH3), 1.94 (s, 3H,
145.4, 140.8, 138.3, 127.7, 127.2, 124.9, 123.5, 111.1, 50.9, 34.3,
30.1, 20.2, 16.9. ESI-HRMS (m/z): Calcd for C21H26N5O2 [M+H]+
380.2081. Found 380.2086.