BULLETIN OF THE
Article
Antiproliferative [1,2,3]Triazolo[4,5-d]pyrimidine Derivatives
KOREAN CHEMICAL SOCIETY
3-(3,5-Dimethoxyphenethyl)-N-(6-morpholinopyridin-
4H), 2.20 (brs, 1H), 1.83 (brs, 2H), 1.71 (brs, 2H), 1.55 (d,
J = 11.8 Hz, 1H), 1.15 (brs, 4H), 1.08–1.02 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ [ppm]: 160.97, 156.77, 152.78,
149.09, 148.95, 139.23, 129.16, 124.92, 123.30, 116.30,
106.68, 99.05, 63.48, 55.25, 49.73, 48.98, 47.88, 35.91,
29.00, 26.33, 25.87.
3-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine (11). It
waspurified byflash column chromatography (silica gel, ethyl
acetate followed by ethyl acetate-methanol 4:1 v/v). White
1
solid; H NMR (400 MHz, CDCl3) δ [ppm]: 8.51 (s, 2H),
8.50 (s, 1H), 8.01 (brs, 1H), 6.71 (d, J = 9.0 Hz, 1H), 6.36
(s, 2H), 6.32 (s, 1H), 4.84 (t, J = 7.8 Hz, 2H), 3.84 (t, J =
4.5 Hz, 4H), 3.74 (s, 6H), 3.52 (t, J = 4.5 Hz, 4H), 3.29 (t, J
= 7.8 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ [ppm]:
161.00, 157.31, 156.77, 156.58, 153.05, 149.08, 142.33,
139.15, 132.81, 125.12, 124.87, 106.37, 99.03, 66.74,
55.26, 47.97, 45.84, 35.91. MS (ESI+) m/z: 484.9 [M +
Na]+, 462.8 [M + H]+. MS (ESI−) m/z: 460.9 [M–H]−.
3-(3,5-Dimethoxyphenethyl)-N-(2-morpholinoethyl)-3H-
[1,2,3]triazolo[4,5-d]pyrimidin-7-amine (16). It was purified
by flash column chromatography (silica gel, methylene chlo-
1
ride-methanol 30:1 v/v). White solid; H NMR (400 MHz,
CDCl3) δ [ppm]: 8.44 (s, 1H), 7.09 (s, 1H), 6.34 (s, 2H),
6.29 (s, 1H), 4.79 (t, J = 8.0 Hz, 2H), 3.77–3.72 (m, 12H),
3.25 (t, J = 8.0 Hz, 2H), 2.68 (t, J = 4.0 Hz, 2H), 2.52 (brs,
4H). 13C NMR (100 MHz, CDCl3) δ [ppm]: 160.92,
156.76, 154.63, 148.53, 139.23, 124.82, 106.66, 98.97,
66.83, 56.79, 55.25, 53.38, 47.76, 36.93, 35.88. MS (ESI+)
m/z: 436.0 [M + Na]+. MS (ESI−) m/z: 411.7 [M–H]−.
3-(3,5-Dimethoxyphenethyl)-N-(4-(4-ethylpiperazin-1-yl)
phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine (17). It
was purified by flash column chromatography (silica gel,
methylene chloride-methanol 40:1 v/v). Yellow solid; 1H
NMR (400 MHz, CDCl3) δ [ppm]: 8.79 (s, 1H), 8.52 (s,
1H), 7.63 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 6.35
(s, 2H), 6.31 (s, 1H), 4.82 (t, J = 8.0 Hz, 2H), 3.72 (s, 6H),
3.27 (t, J = 8.0 Hz, 2H), 3.22 (t, J = 4.0 Hz, 4H), 2.62 (t, J =
4.0 Hz, 4H), 2.48 (q, J = 8.0 Hz, 2H), 1.14 (t, J = 8.0 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ [ppm]: 160.94,
156.77, 152.74, 148.90, 139.20, 129.35, 124.89, 123.26,
116.38, 106.67, 99.01, 55.27, 52.75, 52.33, 49.21, 47.89,
35.91, 11.97. MS (ESI+) m/z: 510.8 [M + Na]+, 488.9 [M +
H]+. MS (ESI−) m/z: 487.1 [M–H]−.
3-(3,5-Dimethoxyphenethyl)-N-(4-(piperidin-1-yl)phenyl)-
3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine (12). It was
1
purified by precipitation from methanol. Yellow solid; H
NMR (400 MHz, CDCl3) δ [ppm]: 8.54 (s, 1H), 8.13 (s,
1H), 7.61 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.36
(s, 2H), 6.32 (s, 1H), 4.83 (t, J = 7.2 Hz, 2H), 3.74 (s, 6H),
3.29 (t, J = 7.2 Hz, 2H), 3.16 (brs, 4H), 1.72 (brs, 4H), 1.58
(brs, 2H). 13C NMR (100 MHz, CDCl3) δ [ppm]: 161.00,
156.81, 152.69, 149.92, 148.89, 139.22, 128.72, 124.93,
122.95, 116.90, 106.10, 99.10, 55.26, 50.79, 47.94, 35.97,
25.81, 24.26. MS (ESI+) m/z: 482.0 [M + Na]+. MS (ESI−)
m/z: 457.9 [M–H]−.
3-(3,5-Dimethoxyphenethyl)-N-(3-morpholinopropyl)-
3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine (13). It was
purified by flash column chromatography (silica gel, methyl-
ene chloride-methanol 15:1 v/v, NH4OH 1%). White solid; 1H
NMR (400 MHz, CDCl3) δ [ppm]: 8.62 (s, 1H), 8.36 (s, 1H),
6.28 (s, 2H), 6.23 (s, 1H), 4.72 (t, J = 8.0 Hz, 2H), 3.77 (t, J =
4.1 Hz,4H),3.74–3.70(m,2H),3.65(s,6H),3.21(t,J = 8.0 Hz,
2H), 2.52(t, J = 8.0 Hz, 2H), 2.45 (brs, 4H), 1.86–1.81 (m, 2H).
13C NMR (100 MHz, CDCl3) δ [ppm]: 160.88, 156.81, 154.59,
148.39, 139.31, 124.98, 106.60, 98.94, 66.78, 57.97, 55.18,
53.74, 47.63, 40.92, 35.83, 24.33. MS (ESI+) m/z: 449.8 [M
+ Na]+, 428.1 [M + H]+. MS (ESI−) m/z: 425.9 [M–H]−.
3-(3,5-Dimethoxyphenethyl)-N-(4-(pyrrolidin-1-yl)
phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine (14).
It was purified by precipitation from methanol. Yellow solid;
1H NMR (400 MHz, CDCl3) δ [ppm]: 8.42 (s, 1H), 8.16 (s,
1H), 7.44 (brs, 2H), 6.51 (d, J = 7.7 Hz, 2H), 6.28 (s, 2H),
6.24 (s, 1H), 4.73 (t, J = 7.2 Hz, 2H), 3.66 (s, 6H), 3.21 (brs,
6H), 1.93 (brs, 4H). 13C NMR (100 MHz, CDCl3) δ [ppm]:
160.99, 156.90, 152.96, 148.81, 146.14, 139.30, 125.26,
124.94, 124.03, 111.45, 106.70, 99.10, 55.36, 47.87, 47.77,
35.97, 25.14. MS (ESI+) m/z: 467.9 [M + Na]+. MS (ESI−)
m/z: 443.9 [M–H]−.
3-(3,5-Dimethoxyphenethyl)-N-(4-(4-(dimethylamino)
piperidin-1-yl)phenyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-
7-amine (18). It was purified by flash column chromatography
(silica gel, methylene chloride-methanol 18:1 v/v). Yellow
1
solid; H NMR (400 MHz, CDCl3) δ [ppm]: 8.45 (s, 1H),
8.41 (s, 1H), 7.57 (d, J = 8.3 Hz, 2H), 6.88 (d, J = 8.3 Hz,
2H), 6.27 (s, 2H), 6.23 (s, 1H), 4.75 (t, J = 7.5 Hz, 2H),
3.70–3.65 (m, 8H), 3.20 (t, J = 7.5 Hz, 2H), 2.79 (t, J = 11.0
Hz, 1H), 2.68 (t, J = 11.0 Hz, 2H), 2.53 (s, 6H), 2.08 (d, J =
11.0 Hz, 2H), 1.72 (q, J = 11.0 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ [ppm]: 160.97, 156.70, 152.69, 148.95,
148.31, 139.20, 129.79, 124.91, 123.18, 117.22, 106.71,
99.01, 62.84, 54.63, 49.72, 47.89, 40.31, 35.89, 26.82.
3-(3-(3,5-Dimethoxyphenethyl)-3H-[1,2,3]triazolo[4,5-
d]pyrimidin-7-ylamino)propan-1-ol (19). It was purified
by flash column chromatography (silica gel, methylene
chloride-methanol 30:1 v/v). Buff solid; 1H NMR (400
MHz, CDCl3) δ [ppm]: 8.45 (s, 1H), 8.11 (brs, 1H),
6.35–6.31 (m, 3H), 4.84 (t, J = 8.0 Hz, 2H), 4.50 (brs, 1H),
3.91 (q, J = 8.0 Hz, 2H), 3.74 (s, 6H), 3.69 (brs, 2H), 3.28
(t, J = 8.0 Hz, 2H), 1.96–1.90 (m, 2H). 13C NMR (100
MHz, CDCl3) δ [ppm]: 160.94, 156.78, 155.32, 148.46,
139.11, 124.64, 106.71, 98.91, 58.51, 55.28, 47.91, 37.26,
35.84, 32.37. MS (ESI+) m/z: 380.8 [M + Na]+, 358.8 [M +
H]+. MS (ESI−) m/z: 356.9 [M–H]−.
N-(4-(4-Cyclohexylpiperazin-1-yl)phenyl)-3-(3,5-dimethox-
yphenethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-amine
(15). It was purified by flash column chromatography (silica
gel, methylene chloride-methanol 20:1 v/v). Yellowish white
solid; 1H NMR (400 MHz, CDCl3) δ [ppm]: 8.50 (brs, 1H),
8.43 (s, 1H), 7.52 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz,
2H), 6.25 (s, 2H), 6.21 (s, 1H), 4.72 (t, J = 7.1 Hz, 2H), 3.62
(s, 6H), 3.18 (t, J = 7.1 Hz, 2H), 3.10 (brs, 4H), 2.63 (brs,
Bull. Korean Chem. Soc. 2015, Vol. 36, 1863–1873
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim