Month 2016
Synthesis, Antiplatelet Aggregation Activity Evaluation and 3D-QSAR of a Series of
Novel 6-Alkylamino(Alkoxyl)-2-Propylthio-8-Azapurine Nucleosides
SCH2CH2CH3), 2.95 (2H, t, J= 7.47 Hz, NHCH2CH2), 1.71
(2H, sextet, J=7.35Hz, SCH2CH2CH3), 0.98 (3H, t,
J=7.35Hz, SCH2CH2CH3); 13C NMR (100MHz,
DMSO-d6): δ= 170.00, 152.94, 149.26, 139.08, 128.60,
128.33, 126.17, 123.01, 89.40, 85.98, 72.63, 70.69, 61.93,
41.55, 34.49, 32.47, 22.56, 13.27. ESI-HRMS: m/z [M + H]+
calcd for: C20H26N6O4S: 447.1814; found: 447.1812.
methylbenzylamine according to the general procedure. The
product was purified by flash column chromatography
(EtOAc/CH2Cl2, 3:1, v/v) and recrystallized in EtOAc and
petroleum ether to give 1d as white powder. Yield: 87%, mp
94–95°C; IR (KBr): 3293, 2960, 1620, 1515, 1460, 1325,
;
1283, 1234, 1179, 1077, 1047, 790 cmÀ1 1H NMR
(400 MHz, DMSO-d6): δ=9.59 (1H, t, J=6.11Hz, NH),
7.12–7.27 (4H, m, Ar), 6.08 (1H, d, J=4.83Hz, H-1′), 5.55
(1H, d, J= 5.85 Hz, OH-2′), 5.27 (1H, d, J= 5.60Hz, OH-
3′), 4.80–4.90 (2H, m, H-2′, OH-5′), 4.68 (2H, d,
J=6.11Hz, NHCH2), 4.29 (1H, q, J=5.09Hz, H-3′), 3.99
(1H, q, J=4.33Hz, H-4′), 3.59–3.64 (1H, m, H-5′α), 3.45–
3.51 (1H, m, H-5′β), 3.04 (2H, m, SCH2CH2CH3), 2.26
(3H, s, ArCH3), 1.64 (2H, sextet, J=7.38Hz,
SCH2CH2CH3), 0.93 (3H, t, J=7.38Hz, SCH2CH2CH3);
13C NMR (100 MHz, DMSO-d6): δ=170.00, 152.92,
149.35, 135.95, 135.69, 128.84, 127.12, 123.02, 89.45,
85.97, 72.61, 70.68, 61.91, 32.40, 22.50, 20.63, 13.22. ESI-
HRMS: m/z [M+H]+ calcd for: C20H26N6O4S: 447.1814;
found: 447.1811.
6-Phenylpropylamino-2-propylthio-8-azapurine nucleoside
(1b). Compound 7 was allowed to react with 3-
phenylpropylamine according to the general procedure. The
product was purified by flash column chromatography
(EtOAc/CH2Cl2, 5:1, v/v) and recrystallized in EtOAc and
petroleum ether to give 1b as white powder. Yield: 91%, mp
151–152°C; IR (KBr): 3291, 2930, 1623, 1591, 1323, 1282,
1230, 1179, 1141, 1075,790, 746, 698 cmÀ1 1H NMR
;
(400 MHz, DMSO-d6): δ =9.13 (1H, t, J=5.61Hz, NH),
7.16–7.30 (5H, m, Ar), 6.07 (1H, d, J=5.04Hz, H-1′), 5.56
(1H, d, J=6.01 Hz, OH-2′), 5.26 (1H, d, J=5.47 Hz, OH-3′),
4.81–4.86 (2H, m, H-2′, OH-5′), 4.28 (1H, q, J=4.61Hz, H-
3′), 3.98 (1H, q, J=4.72Hz, H-4′), 3.59–3.64 (1H, m, H-
5′α), 3.44–3.55 (3H, m, H-5′β, NHCH2), 3.05 (2H, m,
SCH2CH2CH3), 2.67 (2H, t, J= 7.50 Hz, NHCH2CH2CH2),
1.94 (2H, sextet, J=7.17Hz, NHCH2CH2CH2), 1.68 (2H,
sextet, J=7.17Hz, SCH2CH2CH3), 0.97 (3H, t, J=7.35Hz,
SCH2CH2CH3); 13C NMR (100 MHz, DMSO-d6):
δ= 169.94, 153.04, 149.25, 141.48, 128.26, 128.24, 125.73,
123.06, 89.43, 85.97, 72.61, 70.69, 61.94, 42.78, 32.51,
32.43, 30.19, 22.54, 13.25. ESI-HRMS: m/z [M +H]+ calcd
for: C21H28N6O4S: 461.1971; found: 461.1971.
6-(4-Fluorobenzylamino)-2-propylthio-8-azapurine nucleoside
(1e). Compound
7 was allowed to react with 4-
fluorobenzylamine according to the general procedure. The
product was purified by flash column chromatography
(EtOAc/P.E., 1:1, v/v) and recrystallized in EtOAc and
petroleum ether to give 1e as white powder. Yield: 88%, mp
151–152°C; IR (KBr): 3304, 2930, 1621, 1510, 1427, 1326,
1
1224, 1180, 1128, 1076, 1048, 824, 790 cmÀ1; H NMR
(400 MHz, DMSO-d6): δ=9.62 (1H, t, J=6.05Hz, NH),
7.13–7.44 (4H, m, Ar), 6.09 (1H, d, J=5.05Hz, H-1′), 5.56
(1H, d, J= 5.91 Hz, OH-2′), 5.27 (1H, d, J= 5.44Hz, OH-
3′), 4.82–4.88 (2H, m, H-2′, OH-5′), 4.71 (2H, d,
J=6.22Hz, NHCH2), 4.29 (1H, q, J=4.97Hz, H-3′), 4.00
(1H, q, J=4.82Hz, H-4′), 3.59–3.65 (1H, m, H-5′α), 3.46–
3.51 (1H, m, H-5′β), 3.04 (2H, m, SCH2CH2CH3), 1.63
(2H, sextet, J=7.31Hz, SCH2CH2CH3), 0.92 (3H, t,
J=7.15Hz, SCH2CH2CH3); 13C NMR (100 MHz,
DMSO-d6): δ= 170.03, 162.40, 160.00, 152.92, 149.36,
134.91, 134.88, 129.15, 129.07, 123.03, 115.15, 89.46,
85.98, 72.61, 70.68, 61.91, 42.55, 32.40, 22.46, 13.20. ESI-
HRMS: m/z [M + H]+ calcd for: C19H23FN6O4S: 451.1564;
found: 451.1557.
6-Phenylbutylamino-2-propylthio-8-azapurine nucleoside (1c).
Compound 7 was allowed to react with 4-phenylbutylamine
according to the general procedure. The product was purified
by flash column chromatography (EtOAc/CH2Cl2, 10:1, v/v)
and recrystallized in EtOAc and petroleum ether to give 1c
as white powder. Yield: 92%, mp 158–160°C; IR (KBr):
3421, 3330, 2933, 1627, 1593, 1428, 1346, 1317, 1283,
1119, 1078, 1047, 892, 748, 699 cmÀ1; 1H NMR (400 MHz,
DMSO-d6): δ=9.10 (1H, t, J=5.73 Hz, NH), 7.14–7.28 (5H,
m, Ar), 6.06 (1H, d, J=5.08Hz, H-1′), 5.55 (1H, d,
J = 5.94 Hz, OH-2′), 5.26 (1H, d, J = 5.45 Hz, OH-3′),
4.80–4.87 (2H, m, H-2′, OH-5′), 4.28 (1H, q,
J = 4.57 Hz, H-3′), 3.98 (1H, q, J = 4.75 Hz, H-4′),
3.58–3.64 (1H, m, H-5′α), 3.44-3.54 (3H, m, H-5′β,
NHCH2), 3.07 (2H, m, SCH2CH2CH3), 2.61 (2H, t,
J = 6.86 Hz, NHCH2CH2CH2CH2), 1.63–1.74 (6H, m,
NHCH2CH2CH2CH2, SCH2CH2CH3), 0.99 (3H, t,
J = 7.31 Hz, SCH2CH2CH3); 13C NMR (100 MHz,
DMSO-d6): δ= 169.46, 153.00, 149.24, 142.02, 128.25,
128.18, 125.62, 123.03, 89.44, 85.97, 72.61, 70.70,
61.94, 34.76, 32.42, 28.40, 28.22, 22.65, 22.61, 13.28.
ESI-HRMS: m/z [M + H]+ calcd for: C22H30N6O4S:
475.2127; found: 475.2127.
6-(4-Methoxyphenethylamino)-2-propylthio-8-azapurine
nucleoside (1f). Compound 7 was allowed to react with 4-
methoxyphenethylamine according to the general procedure.
The product was purified by flash column chromatography
(EtOAc/P.E., 1:1, v/v) and recrystallized in EtOAc and
petroleum ether to give 1f as white powder. Yield: 90%,
mp 99–100°C; IR (KBr): 3290, 2956, 2930, 2869, 2837,
1622, 1593, 1513, 1456, 1324, 1283, 1246, 1179, 1078,
1
1039cmÀ1; H NMR (400MHz, DMSO-d6): δ=9.14 (1H,
t, J=5.57Hz, NH), 6.85–7.24 (4H, m, Ar), 6.07 (1H, d,
J=5.07Hz, H-1′), 5.55 (1H, d, J=6.02Hz, OH-2′), 5.27
(1H, d, J=5.33Hz, OH-3′), 4.82–4.86 (2H, m, H-2′, OH-
6-(4-Methylbenzylamino)-2-propylthio-8-azapurine nucleoside
(1d). Compound
7 was allowed to react with 4-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet