A. Salgado et al. / Journal of Molecular Structure 987 (2011) 13–24
23
cooling down to RT, dichloromethane (10 mL) was added and ex-
cess 4-fluorobenzylamine hydrochloride was removed by filtra-
tion. The filtrate was evaporated and chromatographed (silica, 5–
10% MeOH in dichloromethane). N-(4-fluorobenzyl)-2-(4-meth-
oxy-phenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-6-amine (5a, 36 mg,
19%) was obtained as a white solid. 1H NMR (700 MHz, DMSO-
d6) d 8.56 (s, 1H), 8.36 (s, 1H), 8.05 (d, J = 7.7 Hz, 1H), 7.57–7.42
(m, 2H), 7.19 (t, J = 8.3 Hz, 2H), 7.06 (d, J = 8.3 Hz, 2H), 6.78 (t,
J = 5.1 Hz, 1H), 4.31 (d, J = 5.4 Hz, 2H), 3.82 (s, 3H). 13C NMR
(75 MHz, DMSO-d6) d 162.5, 161.4 (1JC–F = 242 Hz), 160.7, 150.60,
148.12, 135.61, 134.4 (4JC–F = 2.6 Hz), 129.7 (3JC–F = 8.3 Hz), 127.9,
123.4, 115.3 (2JC–F = 20.9 Hz), 114.3, 114.0, 55.3, 45.9. 15N NMR
(70 MHz, DMSO-d6): as in Table 3. HRMS (ESI+): C19H16FN5O+ re-
quires m/z 349.1333; C19H17FN5O+ (M+H+)+ requires m/z
350.1411; found m/z 350.1435
yellow solid. 1H NMR (700 MHz, DMSO-d6) d 9.84 (s, 1H), 8.54 (s,
1H), 8.34 (s, 1H), 7.94 (d, J = 8.3 Hz, 2H), 7.48 (s, 2H), 7.19 (t,
J = 8.3 Hz, 2H), 6.87 (d, J = 8.3 Hz, 2H), 6.75 (s, 1H), 4.30 (d,
J = 5.4 Hz, 2H). 13C NMR (75 MHz, DMSO-d6) d 162.9, 161.4 (1JC-
F = 243 Hz), 159.1, 150.6, 147.8, 135.4, 134.4 (4JC–F = 2.8 Hz),
129.7 (3JC–F = 7.7 Hz), 127.9, 121.8, 115. 6, 115.2 (2JC–F = 21.5 Hz),
114.0, 45.8. 15N NMR (70 MHz, DMSO-d6): as in Table 6. HRMS
(ESI+): C18H14FN5O+ requires m/z 335.1177; C18H15FN5O+ (M+H)+
requires m/z 336.1255; found m/z 336.1290.
4.15. N-(Tetrahydro-2H-pyran-4-yl)-2-(3,4-dimethoxyphenyl)-
[1,2,4]triazolo[1,5-a]pyrimidin-5-amine (5e)
Compound 4d (200 mg, 0.60 mmol, 1.0 eq) and 4-aminotetra-
hydropyrane (241 mg, 2.39 mmol, 4 eq) were dissolved in TFE
(1.5 mL) and the reaction mixture was irradiated under microwave
conditions (200 W, 170 °C, 30 min). N-(Pyran-4-yl)-2-(3,4-dime-
thoxyphenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-5-amine (5e, 38 mg,
18%) was obtained as a white solid after purification by column
chromatography (silica, 4–10% MeOH in dichloromethane). 1H
NMR (700 MHz, DMSO-d6) d 8.33 (s, 1H), 8.22 (s, 1H), 7.84 (s,
1H), 7.77 (s, 1H), 7.12 (s, 1H), 6.60 (s, 1H), 3.93 (s, 3H), 3.88 (s,
3H), 3.84 (s, 3H), 3.46 (s, 2H), 1.86 (s, 4H). 13C NMR (75 MHz,
DMSO-d6) d 162.9, 156.0, 153.0, 150.7, 148.8, 147.0, 123.1, 120.1,
111.7, 110.1, 89.0, 66.0, 55.6, 55.5, 48.8, 31.7. 15N NMR (70 MHz,
4.12. N-(Cyclopropylmethyl)-2-(3-acetylphenyl)-[1,2,4]triazolo[1,5-
a]pyrimidin-6-amine (5b)
Compound 4b (500 mg, 1.58 mmol, 1 eq) and cyclopropanem-
ethylamine (0.8 mL, 9.24 mmol) were stirred at RT for 30 min. Re-
moval of excess amine by evaporation and purification by column
chromatography (silica, 2–10% MeOH in dichloromethane) gave N-
(cyclopropylmethyl)-2-(3-acetylphenyl)-[1,2,4]triazolo[1,5-a]pyr-
imidin-6-amine (5b, 80 mg, 17%) as a pale yellow solid. 1H NMR
(700 MHz, DMSO-d6) d 8.67 (s, 1H), 8.60 (s, 1H), 8.43 (s, 1H), 8.36
(d, J = 7.7 Hz, 1H), 8.06 (d, J = 7.2 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H),
6.34 (s, 1H), 2.92 (d, J = 6.6 Hz, 2H), 2.66 (s, 3H), 1.12 (s, 1H), 0.53
(d, J = 7.2 Hz, 2H), 0.27 (d, J = 3.6 Hz, 2H). 13C NMR (75 MHz,
DMSO-d6) d 197.6, 161.4, 150.4, 148.7, 137.3, 136. 5, 131.4,
130.6, 129.5, 129.4, 125.6, 113.2, 47.7, 26.8, 10.0, 3.6. 15N NMR
(70 MHz, DMSO-d6): as in Table 4. HRMS (ESI+): C17H17N5O+ re-
quires m/z 307.1428; C17H18N5O+ (M+H)+ requires m/z 308.1506;
found m/z 308.1528.
DMSO-d6): as in Table 7. HRMS (ESI+): C18H21N5Oþ requires m/z
3
355.1639; C18H22N5Oþ (M+H)+ requires m/z 356.1717; found m/z
3
356.1779.
4.16. N-Propyl-2-(3,4-dimethoxyphenyl)-[1,2,4]triazolo[1,5-
a]pyrimidin-5-amine (5f)
Compound 4d (300 mg, 0.90 mmol, 1.0 eq) and propylamine
(0.294 mL, 3.58 mmol, 4 eq) were dissolved in TFE (2 mL). The
reaction mixture was irradiated under microwave conditions
(200 W, 170 °C, 30 min) and the solvent was removed by evapora-
tion. The residue was purified by column chromatography (silica,
4–10% MeOH in dichloromethane). N-(Propyl)-2-(3,4-dimethoxy-
phenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-5-amine (5f, 33 mg, 12%)
was obtained as a beige solid. 1H NMR (700 MHz, DMSO-d6) d
8.30 (d, J = 5.4 Hz, 2H), 7.82 (d, J = 8.3 Hz, 1H), 7.76 (s, 1H), 7.12
(d, J = 8.3 Hz, 1H), 6.42 (d, J = 4.8 Hz, 1H), 3.87 (s, 3H), 3.84 (s,
3H), 3.39 (d, J = 6.6 Hz, 2H), 1.67 (dd, J = 14.3, 7.2 Hz, 2H), 0.94 (t,
J = 7.2 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d 162.9, 156.4,
153.6, 150.6, 148.8, 147.7, 123.4, 119.9, 111.7, 109.9, 88.3, 55.6,
55.5, 43.3, 21.7, 11.1. 15N NMR (70 MHz, DMSO-d6): as in Table 8.
HRMS (ESI+): C16H19N5Oþ requires m/z 313.1533; C16H20N5Oþ
4.13. N-(3,4-Dichlorobenzyl)-2-(4-carboxyphenyl)-[1,2,4]triazolo[1,5-
a]pyrimidin-6-amine (5c)
Compound 4c (360 mg, 1.13 mmol, 1 eq) and 3,4-dichloroben-
zylamine (0.7 mL, 5.31 mmol) were heated at 100 °C for 1 h. Excess
amine was removed by evaporation and residue was purified by
column chromatography (silica, 5–15% MeOH in dichlorometh-
ane). N-(3,4-Dichlorobenzyl)-2-(4-carboxyphenyl)-[1,2,4]triazol-
o[1,5-a]pyrimidin-6-amine (5c, 30 mg, 6%) was obtained as a
yellow solid. 1H NMR (700 MHz, DMSO-d6) d 13.08 (s, 1H), 8.63
(s, 1H), 8.43 (s, 1H), 8.23 (d, J = 6.6 Hz, 2H), 8.06 (d, J = 6.0 Hz,
2H), 7.73 (s, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.44 (d, J = 7.7 Hz, 1H),
6.99 (s, 1H), 4.37 (s, 2H). 13C NMR (75 MHz, DMSO-d6) d 166.9,
161.4, 150.6, 148.9, 139.6, 135.7, 134.774, 131.770, 131.1, 130.6,
129.9, 129.6, 129.6, 127.9, 126.3, 113.9, 45.2. 15N NMR (70 MHz,
2
2
(M+H)+ requires m/z 314.1611; found m/z 314.1679.
DMSO-d6): as in Table 5. HRMS (ESI+): C19H13Cl2N5Oþ requires
4.17. N-(2-Methoxyethyl)-2-(3,4-dimethoxyphenyl)-
[1,2,4]triazolo[1,5-a]pyrimidin-5-amine (5g)
2
m/z 413.0441; C19H14Cl2N5Oþ (M+H)+ requires m/z 414.0519;
2
found m/z 414.0534
Compound 4d (300 mg, 0.90 mmol, 1.0 eq) and 2-methoxyeth-
ylamine (0.31 mL, 3.58 mmol, 4 eq) were dissolved in TFE (2 mL).
The mixture was irradiated under microwave conditions (200 W,
170 °C, 30 min). Column chromatography (silica, 4–10% MeOH in
dichloromethane) gave N-(2-methoxyethyl)-2-(3,4-dimethoxy-
phenyl)-[1,2,4]triazolo[1,5-a]pyrimidin-5-amine (5g, 95 mg, 32%)
as a pale yellow solid. 1H NMR (700 MHz, DMSO-d6) d 8.31 (d,
J = 5.4 Hz, 1H), 8.21 (s, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.76 (s, 1H),
7.12 (d, J = 8.3 Hz, 1H), 6.47 (d, J = 5.4 Hz, 1H), 3.87 (s, 3H), 3.84
(s, 3H), 3.61 (dd, J = 11.9, 4.2 Hz, 5H), 3.28 (s, 1H). 13C NMR
(75 MHz, DMSO-d6) d 163.0, 156.3, 153.60, 150.6, 148.8, 147.8,
123.3, 119.9, 111.7, 109.9, 88.6, 70.1, 58.1, 55.6, 55.5, 41.5. 15N
NMR (70 MHz, DMSO-d6): as in Table 9. HRMS (ESI+):
4.14. N-(4-Fluorobenzyl)-2-(4-hydroxyphenyl)-[1,2,4]triazolo[1,5-
a]pyrimidin-6-amine (5d)
Compound 5a (110 mg, 0.32 mmol, 1.0 eq) was suspended in
dichloromethane (4 mL) and boron tribromide (2.2 mL of a 1 M
solution in dichloromethane, 2.2 mmol) was added dropwise at
RT. The reaction mixture was stirred for 2.5 h at RT, MeOH
(5 mL) was slowly added and the mixture was stirred for additional
30 min. The solvent was evaporated and the residue was purified
by column chromatography (silica, 2–10% MeOH in dichlorometh-
ane). N-(4-Fluorobenzyl)-2-(4-hydroxyphenyl)-[1,2,4]triazolo[1,5-
a]pyrimidin-6-amine (5d, 38 mg, 36%) was obtained as a pale