Month 2015
Synthesis, and Antiviral Bioactivity of Novel 2-Substituted Methlthio-5-(4-Amino-
-Methylpyrimidin-5-yl)-1,3,4-Thiadiazole Derivatives
2
5
-(5-(Benzylthio)-1,3,4-thiadiazole-2-yl)-2-methylpyrimidin-
Anal. Calcd for C H N OS : C 44.42, H 5.08, N 23.55;
found C 44.38, H 5.00, N 23.39.
1
1
15
5
2
4
-amine (9m). Pale yellow solid; mp 209 ~ 210°C; yield
78.50%; IR (KBr): ν 3356.1, 3084.1, 1633.7, 1591.2,
5
-(5-(3,3-Dimethoxypropylthio)-1,3,4-thiadiazole-2-yl)-2-
methylpyrimidin-4-amine (9i).
Pale yellow solid; mp
97~ 199°C; yield 42.50%; IR (KBr): ν 3446.7, 3107.3,
971.2, 1639.4, 1550.7, 1458.1, 1419.6, 1373.3, 1116.7,
1539.2, 1456.2, 1423.7, 1379.1, 1051.2, 945.1, 783.1,
ꢀ
1
1
1
2
9
5
693.2, 582.5 cm ; H-NMR (DMSO-d , 500 MHz) δ:
6
8.50 (s, 1H, Pyrimidine-H), 8.09 (s, 2H, NH ), 7.48 (d,
2
ꢀ
1
1
47.0, 781.1, 615.2, 555.5 cm ; H-NMR (DMSO-d ,
00MHz) δ: 8.52 (s, 1H, Primidine-H), 8.06 (s, 2H,
2H, J = 6.85 Hz, Ph-H), 7.35–7.31 (m, 3H, Ph-H), 4.62
6
13
(s, 2H, CH ), 2.41 (s, 3H, CH ); C-NMR (DMSO-d6,
2 3
NH ), 4.51 (q, 1H, J =5.7 Hz, CH), 3.31–3.28 (m, 2H,
125 MHz) δ: 168.54, 166.24, 163.91, 159.15, 157.86,
2
CH ), 3.25 (s, 6H, CH O), 2.41 (s, 3H, CH ), 2.05 (q,
136.81, 129.68, 129.17, 128.30, 103.75, 38.03, 26.01;
(ESI) m/z: 316.2 ([M + H] ); Anal. Calcd for
2
3
1
3
3
+
2
H, J =6.85 Hz, CH2); C-NMR (DMSO-d , 125MHz)
6
δ: 168.68, 166.07, 164.42, 159.14, 158.18, 103.77,
03.10, 53.39, 32.51, 29.70, 26.12; (ESI) m/z: 328.3 ([M
C H N S : C 53.31, H 4.15, N 22.20; found C 53.20,
H 4.29, N 22.21.
5-(5-(2-Chlorobenzylthio)-1,3,4-thiadiazole-2-yl)-2-methyl-
pyrimidin-4-amine (9n). White solid; mp 202~ 203°C;
yield 81.45%; IR (KBr): ν 3444.8, 2963.1, 1653.0,
14 13 5 2
1
+
+
H] ); Anal. Calcd for C H N O S : C 44.02, H 5.23,
1
1 17 5 2 2
N 21.39; found C 44.08, H 5.18, N 21.30.
Methyl 2-(5-(4-amino-2-methylpyrimidin-5-yl)-1,3,4-thiadiazole-
2
8
1
1
-ylthio)-acetate (9j).
White solid; mp 193~ 195°C; yield
4.30%; IR (KBr): ν 3344.7, 3277.0, 3041.7, 2931.8, 1732.0,
631.7, 1593.2, 1527.6, 1508.3, 1456.2, 1436.9, 1377.1,
1635.6, 1558.4, 1541.1, 1506.4, 1456.2, 1417.6, 1375.2,
1242.1, 1045.4, 943.1, 756.1, 576.7cm ; H-NMR
ꢀ
1
1
(DMSO-d , 500 MHz) δ: 8.51 (s, 1H, Primidine-H),
6
ꢀ
1
305.8, 1207.4, 1161.1, 1060.8, 997.2, 785.0, 574.7 cm ;
8.05 (s, 2H, NH ), 7.64 (d, 2H, J = 7.45 Hz, Ph-H),
2
1
H-NMR (DMSO-d , 500MHz) δ: 8.52 (s, 1H, Pyrimidine-
7.51 (d, 2H, J = 7.40 Hz, Ph-H), 7.38–7.34 (m, 2H,
6
1
3
H), 8.05 (s, 2H, NH ), 4.33 (s, 2H, CH ), 3.70 (s, 3H,
CH3), 2.42 (s, 3H, CH3);
1
1
Ph-H), 4.71 (s, 2H, CH ), 2.31 (s, 3H, CH ); C-
2 3
2
2
1
3
C-NMR (DMSO-d6,
NMR (DMSO-d6, 125 MHz) δ: 168.94, 166.88,
163.27, 159.30, 158.40, 134.34, 134.09, 132.29,
130.63, 130.36, 128.21, 103.86, 36.35, 26.28; (ESI)
25 MHz) δ: 168.93, 168.75, 166.56, 163.20, 159.12,
58.17, 103.67, 53.24, 35.47, 26.10; (ESI) m/z: 298.2
+
+
+
(
[M + H] ), 320.2 ([M+Na] ); Anal. Calcd for
m/z: 350.2 ([M+H] ); Anal. Calcd for C H ClN S : C
14
12
5 2
C H N O S : C 40.39, H 3.73, N 23.55; found C 40.29,
H 3.80, N 23.43.
48.06, H 3.46, N 20.02; found C 48.17, H 3.65, N
20.21.
1
0 11 5 2 2
Ethyl 2-(5-(4-amino-2-methylpyrimidin-5-yl)-1,3,4-thiadiazole-
5-(5-(3-Chlorobenzylthio)-1,3,4-thiadiazole-2-yl)-2-methyl-
pyrimidin-4-amine (9o). Pale yellow solid; mp 186~187°
C; yield 89.30%; IR (KBr): ν 3381.2, 3122.7, 2971.3,
2
-ylthio)acetate (9k).
White solid; mp 178~179°C; yield
6.20%; IR (KBr): ν 3356.1, 3113.1, 2964.5, 1734.0,
639.4, 1589.3, 1543.0, 1521.8, 1456.2, 1423.4, 1386.8,
8
1
1
1653.0, 1635.6, 1575.8, 1558.6, 1541.1, 1521.8, 1489.0,
ꢀ
1
1
377.1, 1305.8, 1197.7, 1159.2, 781.1, 567.0 cm ; H-
1456.2, 1417.6, 1373.3, 1242.1, 1095.5, 945.1, 756.1,
ꢀ
1
1
NMR (DMSO-d , 500MHz) δ: 8.53 (s, 1H, Pyrimidine-H),
555.5cm ; H-NMR (DMSO-d , 500MHz) δ: 8.50 (s,
6
6
8
.05 (s, 2H, NH ), 4.32 (s, 2H, CH ), 4.15–4.12 (q, 2H,
1H, Pyrimidine-H), 8.06 (s, 2H, NH ), 7.58 (s, 1H, Ph-H),
2
2
2
J=6.9Hz, CH ), 2.42 (s, 3H, CH ), 1.24–1.21 (t, 3H,
7.46–7.44 (d, 1H, J= 6.9 Hz, Ph-H), 7.39–7.35 (m, 2H,
2
3
13
13
J=6.9Hz, CH3);
C-NMR (DMSO-d6, 125MHz) δ:
Ph-H), 4.63 (s, 2H, CH ), 2.42 (s, 3H, CH ); C-NMR
2
3
1
6
3
68.75, 168.35, 166.56, 163.20, 159.12, 158.19, 103.67,
(DMSO-d6, 125MHz) δ: 168.75, 166.53, 163.41, 159.11,
+
2.05, 35.71, 26.12, 14.53; (ESI) m/z: 312.2 ([M+H] ),
158.20, 139.67, 133.58, 130.97, 129.44, 128.38, 128.21,
+
+
34.2 ([M+Na] ); Anal. Calcd for C H N O S : C 42.43,
103.69, 37.12, 26.12; (ESI) m/z: 350.2 ([M+H] ); Anal.
1
1 13 5 2 2
H 4.21, N 22.49; found C 42.29, H 4.25, N 22.43.
Calcd for C H ClN S : C 48.06, H 3.46, N 20.02; found
14
12
5 2
2
-(5-(4-Amino-2-methylpyrimidin-5-yl)-1,3,4-thiadiazole-2-
C 48.11, H 3.60, N 20.13.
ylthio)-1-phenylethanone (9l). Pale solid; mp 248 ~250°
5-(5-(4-Chlorobenzylthio)-1,3,4-thiadiazole-2-yl)-2-methyl-
C; yield 82.18%; IR (KBr): ν 3354.2, 3086.2, 1668.7,
pyrimidin-4-amine (9p). White solid; mp 210~ 211°C;
yield 79.25%; IR (KBr): ν 3352.2, 3068.7, 2975.3, 1635.6,
1593.2, 1575.8, 1533.4, 1458.1, 1427.3, 1398.3, 1381.0,
1
6
8
8
590.2, 1541.2, 1456.1, 1433.7, 1376.1, 945.1, 786.1,
ꢀ
1
1
95.2, 581.4 cm
; H-NMR (DMSO-d , 500MHz) δ:
6
ꢀ
1 1
.51 (s, 1H, Primidine-H), 8.08 (d, 2H, J= 6.9Hz, Ph-H),
1242.1, 1053.1, 783.1, 584.4 cm ; H-NMR (DMSO-d ,
6
.02 (s, 2H, NH ), 7.70 (t, 1H, J= 8.6Hz, Ph-H), 7.60
500MHz) δ: 8.51 (s, 1H, Pyrimidine-H), 8.06 (s, 2H,
2
(
t, 2H, J = 8.00Hz, Ph-H), 5.19 (s, 2H, CH ), 2.40 (s, 3H,
NH ), 7.50–7.53 (m, 2H, Ph-H), 7.41–7.45 (m, 2H,
2
2
13
13
CH3);
C-NMR (DMSO-d6, 125MHz) δ: 193.04,
Ph-H), 4.63 (s, 2H, CH ), 2.42 (s, 3H, CH ); C-NMR
2
3
1
1
68.68, 166.31, 163.64, 159.10, 158.11, 135.67, 134.50,
(DMSO-d6, 125MHz) δ: 168.74, 166.47, 163.51, 159.12,
29.45, 129.03, 103.71, 40.58, 26.10; (ESI) m/z: 344.2
158.21, 136.20, 132.84, 131.54, 129.10, 103.70, 37.11,
+
+
+
([M + H] ), 366.2 ([M+ Na] ); Anal. Calcd for
26.13; (ESI) m/z: 350.2 ([M +H] ); Anal. Calcd for
C H N OS : C 52.46, H 3.82, N 20.39; found C 52.50,
C H ClN S : C 48.06, H 3.46, N 20.02; found C
15
13
5
2
14 12
5 2
H 3.65, N 20.21.
48.07, H 3.50, N 20.09.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet