Month 2014
Cu(I)-Catalyzed Efficient Synthesis of 2′-Triazolo-nucleoside Conjugates
OH), 6.46 (1H, d, J = 5.86 Hz, C-1′H), 7.03–7.14 (4H, m, C-2″H,
C-3″H, C-5″H, C-6″H), 8.00 (1H, d, J = 8.05 Hz, C-6H), 8.25
(3H, m, C-3″H, C-5″H, C-6″H), 8.00 (1H, d, J = 8.05Hz, C-6H),
1
3
8.23 (1H, s, triazole H), 11.39 (1H, s, NH); C NMR
(100.6 MHz, DMSO-d ): δ 16.13 (Ph-CH ), 60.44 (C-5′), 61.42
(CH OAr), 64.90 (C-2′), 68.48 (C-3′), 85.78 (C-4′), 85.84 (C-1′),
1
3
(
1H, s, triazole H), 11.40 (1H, s, NH); C NMR (100.6MHz,
DMSO-d ): δ 60.43 (C-5′), 61.54 (CH OAr), 64.93 (C-2′), 69.26
C-3′), 85.71 (C-4′), 85.87 (C-1′), 102.41 (C-5), 115.78, 115.97,
6
3
6
2
2
(
102.41 (C-5), 111.95 (C-6″), 120.68 (C-4″), 125.43 (C-2″),
125.95 (C-5 triazole), 127.00 (C-5″), 134.53 (C-3″), 140.03 (C-6),
1
16.01, and 116.06 (C-2″, C-3″, C-5″, C-6″), 125.74 (C-5
triazole), 140.12 (C-6), 142.25 (C-4 triazole), 150.43 (2-C═O),
142.97 (C-4 triazole), 150.44 (2-C═O), 156.27
(C-1″), 163.02
4
1
+
1
54.45 (d, JC–F = 2.01 Hz, C-1″), 155.52 (d, JC–F = 236.41 Hz,
(4-C═O); HR-ESI-TOF-MS: m/z 438.1376 ([M + Na] ), Calcd for
+
C-4″), 163.02 (4-C═O); HR-ESI-TOF-MS: m/z 420.1321
[C19
H
21
N O
5 6
+ Na] : 438.1384.
+
+
2
′-Deoxy-2′-(4-m-tolyloxymethyl-1,2,3-triazol-1-yl)uridine
(
[M + H] ), Calcd for [C H FN O + H] : 420.1314.
18 18 5 6
2
′-Deoxy-2′-(4-p-chlorophenoxymethyl-1,2,3-triazol-1-yl)
(11o). It was obtained as a white solid (0.739 g) in 89% yield by
uridine (11l). It was obtained as a white solid (0.800g) in 92%
silica gel column chromatography using methanol:chloroform in
yield by silica gel column chromatography using methanol:
the ratio 7:93 as an eluent; mp 198–200°C; R = 0.55 (20%
f
À1
chloroform in the ratio 7:93 as an eluent; mp 252–254°C;
methanol in chloroform, v/v); IR (cm , KBr): 3410, 2928, 1752,
À1
1
R
3
f
= 0.55 (20% methanol in chloroform, v/v); IR (cm , KBr):
1685, 1461, 1396, 1238, 1095, and 773; H NMR (400 MHz,
1
410, 2925, 1752, 1686, 1462, 1394, 1230, 1098, and 772; H
DMSO-d ): δ 2.26 (3H, s, Ph-CH ), 3.62–3.65 (1H, m, C-5′H ),
6
3
α
NMR (400MHz, DMSO-d ): δ 3.63–3.67 (1H, m, C-5′H ),
3.73–3.76 (1H, m, C-5′H ), 4.11–4.12 (1H, m, C-4′H), 4.41 (1H,
6
α
β
3
.75–3.79 (1H, m, C-5′H
β
), 4.12–4.13 (1H, m, C-4′H), 4.43 (1H,
OAr),
.31 (1H, t, J=4.39Hz, C-5′OH), 5.43 (1H, t, J=5.86Hz, C-2′H),
2
dd, J = 10.25 Hz and J = 5.13Hz, C-3′H), 5.10 (2H, s, CH OAr),
dd, J = 10.25 Hz and J = 5.13 Hz, C-3′H), 5.15 (2H, s, CH
2
5.32 (1H, brs, C-5′OH), 5.42 (1H, t, J = 5.86Hz, C-2′H), 5.70
(1H, d, J = 8.05 Hz, C-5H), 5.91 (1H, d, J = 5.86Hz, C-3′OH),
6.47 (1H, d, J = 5.86Hz, C-1′H), 6.75 (1H, d, J = 7.32Hz, C-6″
H), 7.81 (1H, d, J = 8.05Hz, C-4″H), 6.85 (1H, s, C-2″H),
7.14–7.18 (1H, m, C-5″H), 8.00 (1H, d, J = 8.05Hz, C-6H), 8.23
5
5
6
.72 (1H, d, J= 8.05 Hz, C-5H), 5.92 (1H, d, J=5.13Hz, C-3′OH),
.48 (1H, d, J=5.86Hz, C-1′H), 7.07 (2H, d, J=8.79Hz, C-2″H,
C-6″H), 7.34 (2H, d, J=8.79Hz, C-3″H, C-5″H), 8.02 (1H, d,
13
13
J= 8.05 Hz, C-6H), 8.27 (1H, s, triazole H), 11.40 (1H, s, NH);
NMR (100.6 MHz, DMSO-d ): δ 60.41 (C-5′), 61.29 (CH OAr),
4.93 (C-2′), 69.24 (C-3′), 85.79 (C-4′), 85.85 (C-1′), 102.40 (C-5),
16.49 (C-2″, C-6″), 124.60 (C-4″), 125.83 (C-5 triazole), 129.30
C
(1H, s, triazole H), 11.39 (1H, s, NH); C NMR (100.6 MHz,
6
2
6 3 2
DMSO-d ): δ 21.17 (Ph-CH ), 60.43 (C-5′), 60.85 (CH OAr),
6
1
64.90 (C-2′), 69.26 (C-3′), 85.78 (C-4′), 85.85 (C-1′), 102.40
(C-5), 111.64 (C-6″), 115.28 (C-2″), 121.65 (C-4″), 125.60 (C-5
triazole), 129.28 (C-5″), 139.07 (C-3″), 140.13 (C-6), 142.47 (C-4
triazole), 150.43 (2-C═O), 158.16 (C-1″), 163.00 (4-C═O);
(C-3″, C-5″), 140.12 (C-6), 142.05 (C-4 triazole), 150.43 (2-C═O),
156.98 (C-1″), 163.00 (4-C═O); HR-ESI-TOF-MS: m/z 436.1019
+
+
+
([M + H] ), Calcd for [C18
H
18ClN
5
O
6
+H] : 436.1018.
HR-ESI-TOF-MS: m/z 438.1382 ([M+ Na] ), Calcd for
+
2
′-Deoxy-2′-(4-p-methoxyphenoxymethyl-1,2,3-triazol-1-yl)
[
C H N O + Na] : 438.1384.
1
9 21 5 6
uridine (11m). It was obtained as a white solid (0.750 g) in 87%
2′-Deoxy-2′-(4-p-tolyloxymethyl-1,2,3-triazol-1-yl)uridine
yield by silica gel column chromatography using methanol:
(11p). It was obtained as a white solid (0.747 g) in 90% yield by
chloroform in the ratio 7:93 as an eluent; mp 193–194°C; R
f
=0.55
silica gel column chromatography using methanol:chloroform in
À1
(
1
20% methanol in chloroform, v/v); IR (cm , KBr): 3410, 2927,
750, 1685, 1460, 1396, 1238, 1095, and 773; H NMR (400 MHz,
f
the ratio 7:93 as an eluent; mp 243–245°C; R = 0.55 (20%
1
À1
methanol in chloroform, v/v); IR (cm , KBr): 3408, 2927, 1750,
1
DMSO-d ): δ 3.63–3.76 (4H, m, C-5′H, Ph-OCH ), 4.11–4.11 (1H,
1685, 1460, 1394, 1238, 1095, and 779; H NMR (400 MHz,
6
3
m, C-4′H), 4.41 (1H, dd, J= 9.52 Hz and J=4.39Hz, C-3′H), 5.05
2H, s, CH OAr), 5.30 (1H, brs, C-5′OH), 5.41 (1H, t, J=6.22Hz,
DMSO-d ): δ 2.23 (3H, s, Ph-CH ), 3.63–3.66 (1H, m, C-5′H ),
6
3
α
(
2
β
3.75–3.78 (1H, m, C-5′H ), 4.12–4.13 (1H, m, C-4′H), 4.44 (1H,
C-2′H), 5.70 (1H, d, J= 8.05 Hz, C-5H), 5.90 (1H, d, J=5.13Hz,
C-3′OH), 6.47 (1H, d, J=5.86Hz, C-1′H), 6.84 (2H, d,
J=8.79Hz, C-2″H, C-6″H), 6.95 (2H, d, J=8.79Hz, C-3″H, C-5″
H), 8.00 (1H, d, J= 8.05 Hz, C-6H), 8.22 (1H, s, triazole H), 11.38
dd, J = 10.25 Hz and J = 5.13Hz, C-3′H), 5.09 (2H, s, CH OAr),
2
5.32 (1H, brs, C-5′OH), 5.43 (1H, t, J = 5.86Hz, C-2′H), 5.71
(1H, d, J = 8.05 Hz, C-5H), 5.92 (1H, d, J = 5.13Hz, C-3′OH),
6.48 (1H, d, J = 5.86 Hz, C-1′H), 6.92 (2H, d, J = 8.79Hz, C-2″H,
C-6″H), 7.09 (2H, d, J = 8.79Hz, C-3″H, C-5″H), 8.02 (1H, d,
J = 8.05 Hz, C-6H), 8.25 (1H, s, triazole H), 11.40 (1H, s, NH);
13
(
1H, s, NH); C NMR (100.6 MHz, DMSO-d
Ph-OCH ), 60.39 (C-5′), 61.48 (CH OAr), 64.87 (C-2′), 69.22
C-3′), 85.72 (C-4′), 85.82 (C-1′), 102.37 (C-5), 114.56 (C-2″,
6
): δ 55.31
(
3
2
13
(
C NMR (100.6MHz, DMSO-d ): δ 20.13 (Ph-CH ), 60.42
6 3
C-6″), 115.59 (C-3″, C-5″), 125.56 (C-5 triazole), 140.09 (C-6, C-4
(C-5′), 60.97 (CH OAr), 64.90 (C-2′), 69.26 (C-3′), 85.77 (C-4′),
2
triazole), 150.39 (2-C═O), 152.11 (C-1″), 153.54 (C-4″), 162.97
85.85 (C-1′), 102.40 (C-5), 114.48 (C-2″, C-6″), 125.61 (C-5
triazole), 129.53 (C-4″), 129.88 (C-3″, C-5″), 140.13 (C-6),
+
(
4-C═O); HR-ESI-TOF-MS: m/z 432.1512 ([M + H] ), Calcd for
+
[
C
19
H
21
N
5
O
7
+H] : 432.1514.
′-Deoxy-2′-(4-o-tolyloxymethyl-1,2,3-triazol-1-yl)uridine
11n). It was obtained as a white solid (0.747 g) in 90% yield
by silica gel column chromatography using methanol:chloroform
142.51 (C-4 triazole), 150.43 (2-C═O), 156.05 (C-1″), 163.00
+
2
(
[
4-C═O); HR-ESI-TOF-MS: m/z 416.1554 ([M + H] ), Calcd for
+
(
C H N O + H] : 416.1565.
19 21 5 6
2′-Deoxy-2′-(4-p-bromophenoxymethyl-1,2,3-triazol-1-yl)
in the ratio 7:93 as an eluent; mp 171–173°C; R
methanol in chloroform, v/v); IR (cm , KBr): 3410, 2927,
f
= 0.55 (20%
uridine (11q).
yield by silica gel column chromatography using methanol:
chloroform in the ratio 7:93 as an eluent; mp 251–252°C; R =0.55
It was obtained as a white solid (0.900 g) in 94%
À1
1
1
750, 1685, 1460, 1396, 1238, 1095, and 773; H NMR
f
À1
(
400 MHz, DMSO-d ): δ 2.12 (3H, s, Ph-CH ), 3.62–3.65 (1H,
(20% methanol in chloroform, v/v); IR (cm , KBr): 3410, 2925,
6
3
1
m, C-5′H ), 3.73–3.76 (1H, m, C-5′H ), 4.11–4.12 (1H, m, C-4′
1754, 1686, 1465, 1395, 1236, 1099, and 778; H NMR (400 MHz,
α
β
H), 4.43–4.45 (1H, m, C-3′H), 5.14 (2H, s, CH
2
OAr), 5.31 (1H,
DMSO-d
), 4.11–4.13 (1H, m, C-4′H), 4.45 (1H, brm, C-3′H), 5.15 (2H, s,
CH OAr), 5.35 (1H, brs, C-5′OH), 5.43 (1H, t, J=5.49Hz, C-2′H),
5.72 (1H, d, J= 8.05 Hz, C-5H), 5.95 (1H, brs, C-3′OH), 6.48
6 α
): δ 3.64–3.66 (1H, m, C-5′H ), 3.75–3.78 (1H, m, C-5′
brs, C-5′OH), 5.42 (1H, t, J = 5.86 Hz, C-2′H), 5.70 (1H, d,
J = 8.05Hz, C-5H), 5.91 (1H, d, J = 3.66 Hz, C-3′OH), 6.48 (1H,
d, J = 6.59Hz, C-1′H), 6.83 (1H, t, J = 7.32 Hz, C-4″H), 7.10–7.17
H
β
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet