D. Gravestock et al. / European Journal of Medicinal Chemistry 46 (2011) 2022e2030
2029
6.91 (d, J ¼ 8.9 Hz, 2H), 4.03 (t, J ¼ 5.9 Hz, 2H), 3.63e3.34 (m, 2H),
2.09e1.96 (m, 2H), 1.88e1.21 (m, 10H); 13C NMR (50 MHz, CD3OD):
4.1.3.21. N6-(3-(2-Chlorophenoxy)propyl)-2-phenyl-1,2-dihydro-
1,3,5-triazine-4,6-diamine hydrochloride (16.21). Yield 27%, as
a clear gum; 1H NMR (400 MHz, CD3OD):
7.51e7.39 (m, 5H), 7.35
d
160.4, 159.9, 159.4, 131.1, 127.5, 117.9, 68.4, 67.8, 39.9, 39.3, 31.3,
d
26.3, 23.2; Compound purity (UPLC): 98.7%; HRMS (ESI): m/z
(d, J ¼ 7.9 Hz, 1H), 7.28e7.21 (m, 1H), 7.05 (d, J ¼ 8.2 Hz, 1H),
6.96e6.89 (m, 1H), 5.75 (s, 1H), 4.13 (t, J ¼ 5.9 Hz, 2H), 3.76e3.56
(m, 1H), 3.56e3.39 (m, 1H), 2.14e2.05 (m, 2H); 13C NMR (101 MHz,
350.1748 (M þ H)þ; calc. for C17H25ClN5O: 350.1748.
4.1.3.15. N6-(3-(4-Chlorophenoxy)propyl)-2-(4-methoxyphenyl)-1,2-
CD3OD): d 159.5, 159.1, 155.7, 140.7, 131.2, 130.9, 130.2, 129.1, 127.6,
dihydro-1,3,5-triazine-4,6-diamine hydrochloride (16.15). Yield 66%,
123.9, 122.7, 115.0, 67.9, 65.1, 39.2, 30.5; Compound purity (UPLC):
96.4%; HRMS (ESI): m/z 358.1437 (M þ H)þ; calc. for C18H21ClN5O:
358.1435.
as a pale yellow viscous oil; 1H NMR (400 MHz, CD3OD):
d 7.35
(d, J ¼ 7.9 Hz, 2H), 7.28e7.19 (m, 2H), 7.04e6.80 (m, 4H), 5.67 (s,1H),
4.03 (t, J ¼ 5.9 Hz, 2H), 3.80 (s, 3H), 3.68e3.34 (m, 2H), 2.17e1.91
(m, 2H); 13C NMR (101 MHz, CD3OD):
d
162.3, 161.5, 159.9, 158.7,
4.1.3.22. N6-(3-(2,4-Dichlorophenoxy)propyl)-2-phenyl-1,2-dihydro-
132.4, 130.3, 129.1, 126.6, 117.0, 115.4, 66.9, 64.8, 55.9, 39.1, 30.4;
Compound purity (UPLC): 97.7%; HRMS (ESI): m/z 388.1540
(M þ H)þ; calc. for C19H23ClN5O2: 388.1540.
1,3,5-triazine-4,6-diamine hydrochloride (16.22). Yield 22%, as
a white solid; 1H NMR (400 MHz, CD3OD):
d 7.59e7.35 (m, 6H),
7.32e7.21 (m, 1H), 7.07 (d, J ¼ 8.8 Hz, 1H), 5.78 (s, 1H), 4.15
(t, J ¼ 5.9 Hz, 2H), 3.55e3.42 (m, 1H), 3.37e3.30 (m, 1H), 2.17e2.08
4.1.3.16. N6-(3-(4-Chlorophenoxy)propyl)-2-(4-(dimethylamino)phen-
(m, 2H); 13C NMR (101 MHz, CD3OD):
d 164.8, 158.7 (2C), 154.6,
yl)-1,2-dihydro-1,3,5-triazine-4,6-diamine hydrochloride (16.16). Yield
140.6, 130.8, 130.6, 130.1, 128.9, 127.5, 124.7, 115.8, 68.2, 64.9, 39.1,
30.3; Compound purity (UPLC): 80.6%; HRMS (ESI): m/z 392.1046
(M þ H)þ; calc. for C18H20Cl2N5O: 392.1045.
64%, as a beige solid; 1H NMR (400 MHz, CD3OD):
d 7.34e7.15 (m,
4H), 6.98e6.82 (m, 2H), 6.81e6.65 (m, 2H), 5.59 (s, 1H), 4.03 (t,
J ¼ 5.6 Hz, 2H), 3.71e3.50 (m, 1H), 3.47e3.33 (m, 1H), 2.95 (s, 6H),
2.10e1.95 (m, 2H); 13C NMR (101 MHz, CD3OD):
d
159.1, 158.9, 153.1,
4.1.3.23. N6-(3-(2-Fluorophenoxy)propyl)-2-phenyl-1,2-dihydro-
130.3,129.9,128.7,127.3,126.6,117.0,113.5, 66.9, 65.1, 40.6, 39.1, 30.4;
Compound purity (UPLC): 89.5%; HRMS (ESI): m/z 401.1855
(M þ H)þ; calc. for C20H26ClN6O: 401.1857.
1,3,5-triazine-4,6-diamine hydrochloride (16.23). Yield 13%, as
a yellow gum; 1H NMR (400 MHz, CD3OD):
d 7.56e7.36 (m, 5H),
7.16e7.02 (m, 3H), 6.92 (ddd, J ¼ 3.8, 6.6, 11.1 Hz, 1H), 5.76 (s, 1H),
4.12 (t, J ¼ 6.0 Hz, 2H), 3.70e3.38 (m, 2H), 2.14e1.99 (m, 2H); 13C
4.1.3.17. N6-(3-(4-Chlorophenoxy)propyl)-2-(4-fluorophenyl)-1,2-dih-
ydro-1,3,5-triazine-4,6-diamine hydrochloride (16.17). Yield 59%, as
NMR (101 MHz, CD3OD): d 161.4, 158.7, 140.7, 130.8, 130.2, 127.5,
125.6 (d, JCeF ¼ 3.9 Hz, 1C), 122.4 (d, JCeF ¼ 6.6 Hz, 1C), 117.0
(d, JCeF ¼ 18.3 Hz, 1C), 116.5 (d, JCeF ¼ 1.3 Hz, 1C), 68.1, 64.9, 39.1,
30.5; Compound purity (UPLC): 71.3%; HRMS (ESI): m/z 342.1732
(M þ H)þ; calc. for C18H21FN5O: 342.1730.
acolourless viscousoil; 1HNMR(400MHz, CD3OD):
d
7.46 (dd, J¼ 5.4,
8.2 Hz, 2H), 7.28e7.21 (m, 2H), 7.20e7.10 (m, 2H), 6.95e6.85 (m, 2H),
5.75 (s, 1H), 4.02 (t, J ¼ 5.9 Hz, 2H), 3.71e3.34 (m, 2H), 2.03 (p,
J ¼ 6.4 Hz, 2H); 13C NMR (50 MHz, CD3OD):
164.8 (d, JCeF ¼ 247.3 Hz,
d
1C),159.0,158.7,158.6,136.8,130.3,129.8 (d, JCeF ¼ 8.6 Hz, 2C),126.6,
117.1 (d, JCeF ¼ 2.8 Hz, 2C), 116.7, 67.0, 64.4, 39.1, 30.4; Compound
purity (UPLC): 97.6%; HRMS (ESI): m/z 376.1336 (M þ H)þ; calc. for
C18H20ClFN5O: 376.1340.
4.1.3.24. N6-(3-(4-Nitrophenoxy)propyl)-2-phenyl-1,2-dihydro-1,3,5-
triazine-4,6-diamine hydrochloride (16.24). Yield 35%, as a white
solid; 1H NMR (400 MHz, CD3OD):
d
8.19 (d, J ¼ 8.4 Hz, 2H),
7.57e7.32 (m, 5H), 7.07 (d, J ¼ 8.5 Hz, 2H), 5.76 (s, 1H), 4.19 (t,
J ¼ 5.8 Hz, 2H), 3.70e3.38 (m, 2H), 2.19e2.00 (m, 2H); 13C NMR
4.1.3.18. N6-(3-(4-Chlorophenoxy)propyl)-2-(4-(trifluoromethyl)
(101 MHz, CD3OD): d 165.5, 158.7, 151.6, 142.8, 140.6, 130.8, 130.1,
phenyl)-1,2-dihydro-1,3,5-triazine-4,6-diamine
(16.18). Yield 51%, as a pale yellow solid; 1H NMR (400 MHz,
CD3OD):
hydrochloride
127.5, 126.8, 115.8, 67.6, 64.9, 38.9, 30.3; Compound purity (UPLC):
88.7%; HRMS (ESI): m/z 369.1674 (M þ H)þ; calc. for C18H21N6O3:
369.1675.
d
7.71 (d, J ¼ 7.6 Hz, 2H), 7.61 (d, J ¼ 7.9 Hz, 2H), 7.28e7.17
(m, 2H), 6.90 (d, J ¼ 7.7 Hz, 2H), 5.85 (s, 1H), 4.02 (t, J ¼ 5.8 Hz, 2H),
3.73e3.34 (m, 2H), 2.03 (p, J ¼ 6.1 Hz, 2H); 13C NMR (101 MHz,
4.1.3.25. N6-(3-(4-Methoxyphenoxy)propyl)-2-phenyl-1,2-dihydro-
CD3OD):
d
160.0, 159.6, 159.1, 158.6, 130.3, 128.3, 126.9 (q,
1,3,5-triazine-4,6-diamine hydrochloride (16.25). Yield 24%, as
JCeF ¼ 3.7 Hz, 2C), 126.6, 123.9 (q, JCeF ¼ 271.5 Hz, 1C), 117.0, 66.7,
64.5, 39.1, 30.2; Compound purity (UPLC): 91.2%; HRMS (ESI): m/z
426.1308 (M þ H)þ; calc. for C19H20ClF3N5O: 426.1308.
a clear gum; 1H NMR (400 MHz, CD3OD):
d 7.53e7.36 (m, 5H),
6.98e6.74 (m, 4H), 5.73 (s, 1H), 3.99 (t, J ¼ 5.9 Hz, 2H), 3.74 (s, 3H),
3.66e3.54 (m, 1H), 3.30e3.24 (m, 1H), 2.08e1.96 (m, 2H); 13C NMR
(101 MHz, CD3OD):
d 159.7, 158.6, 155.4, 154.4, 140.7, 134.4, 130.2,
4.1.3.19. N6-(3-(4-Chlorophenylthio)propyl)-2-phenyl-1,2-dihydro-
127.6, 116.5, 115.6, 67.2, 64.9, 56.1, 39.2, 30.6; Compound purity
(UPLC): 98.8%; HRMS (ESI): m/z 354.1933 (M þ H)þ; calc. for
C19H24N5O2: 354.1930.
1,3,5-triazine-4,6-diamine hydrochloride (16.19). Yield 85%, as a pale
yellow gum; 1H NMR (400 MHz, CD3OD):
d 7.50e7.39 (m, 3H),
7.39e7.23 (m, 6H), 5.75 (s,1H), 3.50 (t, J ¼ 6.5 Hz, 2H), 3.10e2.87 (m,
2H), 1.93 (dt, J ¼ 7.2, 14.5 Hz, 2H); 13C NMR (101 MHz, CD3OD):
4.1.3.26. N6-(4-(4-Chlorophenoxy)butyl)-2,2-dimethyl-1,2-dihydro-
d
159.7, 158.6, 140.8, 135.8, 133.2, 132.0, 130.2, 130.2, 130.1, 127.5,
1,3,5-triazine-4,6-diamine hydrochloride (16.26). Yield 51%, as an
64.8, 40.6, 39.7, 31.2; Compound purity (UPLC): 92.7%; HRMS (ESI):
orange viscous gum; 1H NMR (400 MHz, CD3OD):
d 7.26e7.20 (m,
m/z 374.1155 (M þ H)þ; calc. for C18H21ClN5S: 374.1206.
2H), 6.93e6.85 (m, 2H), 3.99 (t, J ¼ 6.0 Hz, 2H), 3.53e3.34 (m, 1H),
3.34e3.15 (m, 1H), 1.89e1.65 (m, 4H), 1.47 (s, 6H); 13C NMR
4.1.3.20. N6-(3-(4-Chlorophenylthio)propyl)-2,2-dimethyl-1,2-dihy-
(50 MHz, CD3OD): d 160.6, 160.3, 159.2, 131.1, 127.3, 117.9, 69.8, 64.2,
dro-1,3,5-triazine-4,6-diamine hydrochloride (16.20). Yield 86%, as
42.4, 30.0, 28.3, 15.5; Compound purity (UPLC): 98.5%; HRMS (ESI):
a pale yellow gum; 1H NMR (400 MHz, CD3OD):
d
7.40e7.23
(m, 4H), 3.55e3.38 (m, 2H), 2.98 (t, J ¼ 6.9 Hz, 2H), 2.03e1.73
(m, 2H), 1.47 (s, 6H); 13C NMR (101 MHz, CD3OD):
158.4 (2C),131.7,
m/z 324.1587 (M þ H)þ; calc. for C15H23ClN5O: 324.1591.
d
4.1.3.27. N6-(4-(4-Chlorophenoxy)butyl)-2-phenyl-1,2-dihydro-
130.8, 130.1, 127.1, 66.1, 40.6, 31.6, 30.2, 29.1; Compound purity
(UPLC): 89.6%; HRMS (ESI): m/z 326.1207 (M þ H)þ; calc. for
C14H21ClN5S: 326.1206.
1,3,5-triazine-4,6-diamine hydrochloride (16.27). Yield 52%, as an
orange solid; 1H NMR (400 MHz, CD3OD):
d
7.51e7.39 (m, 5H), 7.23
(d, J ¼ 8.9 Hz, 2H), 6.89 (d, J ¼ 8.7 Hz, 2H), 5.74 (s,1H), 4.06e3.90 (m,