ACCEPTED MANUSCRIPT
1
1068, 1032, 978, 861, 818, 763, 749; H NMR (400 MHz,
CDCl3): δ 9.33 (s, 1H), 7.74 (s, 1H), 7.52 (s, 2H), 7.08 (d, J = 8.0
Hz, 1H), 5.75 (d, J = 8.0 Hz, 1H), 5.44 (s, 1H), 5.31 (d, J = 12.4
Hz, 1H), 5.20–5.10 (m, 3H), 4.92–4.88 (m, 2H), 4.70 (d, J = 6.0
Hz, 2H), 4.51 (q, J = 5.6 Hz, 1H), 4.13–4.07 (m, 1H), 3.99–3.93
(m, 1H), 3.61 (s, 3H), 3.42 (s, 3H), 1.54 (s, 3H), 1.35 (s, 3H); 13C
NMR (400 MHz, DMSO-d6): δ 169.8, 167.0, 163.1, 156.8, 150.8,
148.7, 144.1, 142.0, 140.8, 125.6, 123.9, 113.4, 108.2, 101.4,
92.8, 85.6, 83.4, 81.2, 57.8, 48.0, 44.1, 35.6, 30.0, 29.7, 26.8,
25.0; HRMS (ESI): calcd for C26H31N10O10 [M+H]+: 643.2225,
found: 643.2235; m/z (ES)+: 643.6 [M+H]+.
yl)methyl
2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-
7(6H)-yl)acetate (29). White solid; Yield 51%; IR (KBr): υmax
/
cm-1 = 3445, 2986, 2953, 1749, 1699, 1661, 1556, 1463, 1457,
1
1396, 1376, 1230, 1203, 1094, 1038, 813, 763, 749; H NMR
(400 MHz, DMSO-d6): δ 8.15 (s, 1H), 8.05 (s, 1H), 7.53 (d, J =
8.4 Hz, 1H), 5.79 (d, J = 5.2 Hz, 1H), 5.74 (d, J = 8.4 Hz, 1H),
5.52 (d, J = 5.2 Hz, 1H), 5.40 (d, J = 6.0 Hz, 1H), 5.25 (s, 2H),
5.21 (s, 2H), 4.77–4.66 (m, 2H), 4.19–4.15 (m, 1H), 4.11–4.07
(m, 1H), 3.99–3.95 (m, 1H), 3.81(q, J = 6.8 Hz, 2H), 3.44 (s,
3H), 3.19 (s, 3H), 1.07 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz,
DMSO-d6): δ 165.0, 161.1, 156.0, 151.9, 151.0, 147.7, 144.8,
143.8, 141.5, 126.3, 123.3, 105.1, 92.3, 76.4, 73.3, 70.9, 56.3,
50.0, 48.3, 29.6, 26.7, 13.9; HRMS (ESI): calcd for
C23H27N9O9Na [M+Na]+: 596.1829, found: 596.1826; m/z (ES)+:
574.25 [M+H]+.
4.6. General procedure for the synthesis of compounds (27–32)
Sodium ascorbate (2.0 equiv) and CuSO4.5H2O (2.0 equiv)
was added subsequently to a solution of acetylene compounds 6a,
6b, 9 and 13 (1.0 euiv) and corresponding azide compound 18 or
19 (1.1 equiv) in a mixture of ethanol and water (2:1) at room
temperature and stirred for 16 h. After completion of the reaction
as monitored by TLC, the reaction mixture was filtered and the
filtrate was concentrated under reduced pressure. The crude
compounds were purified by prep-TLC, eluted in 5-10% MeOH
in dichloromethane to afford desired products.
4.6.4. (1-((5-(3-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-
3,4-dihydroxytetrahydro furan-2-yl)methyl)-1H-1,2,3-triazol-4-
yl)methyl-2-(2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-
7(6H)-yl)acetamido)acetate (30). White solid; Yield 42%; IR
(KBr): υmax/ cm-1 = 3425, 2986, 2954, 1740, 1718, 1703, 1666,
1557, 1463, 1438, 1383, 1235, 1201, 1052, 1043, 1029, 825, 760,
1
750; H NMR (400 MHz, DMSO-d6): δ 8.70 (t, J = 6.0 Hz, 1H),
8.13 (s, 1H), 8.02 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 5.79–5.74 (m,
2H), 5.52 (d, J = 5.6 Hz, 1H), 5.40 (d, J = 6.0 Hz, 1H), 5.16 (s,
2H), 5.06 (s, 2H), 4.76–4.61 (m, 2H), 4.18–4.10 (m, 2H), 3.99–
3.91 (m, 3H), 3.80 (q, J = 7.6 Hz, 2H), 3.43 (s, 3H), 3.19 (s, 3H),
1.07 (t, J = 6.8 Hz, 3H); m/z (ES)+: 631.31 [M+H]+.
4.6.1. (1-((5-(3-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-
3,4-dihydroxytetrahydro furan-2-yl)methyl)-1H-1,2,3-triazol-4-
yl)methyl
2-(2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-
7(6H)-yl)propanamido)propanoate (27). White solid; Yield 49%;
mp: compound melting starts at 218oC and completely melts at
224oC; IR (KBr): υmax/ cm-1 = 3410, 3323, 3146, 3121, 2977,
2956, 2926, 1733, 1704, 1677, 1657, 1547, 1455, 1349, 1268,
4.6.5. (1-((5-(3-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-
3,4-dimethoxytetrahydro furan-2-yl)methyl)-1H-1,2,3-triazol-4-
1
1238, 1201, 1126, 1077, 1059, 1044, 854, 821, 769, 759; H
yl)methyl
2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-
NMR (400 MHz, DMSO-d6): δ 8.79–8.76 (m, 1H), 8.20–8.08 (m,
2H), 7.58–7.54 (m, 1H), 5.79–5.73 (m, 2H), 5.59–5.52 (m, 2H),
5.41 (d, J = 4.8 Hz, 1H ), 5.19–5.10 (m, 2H), 4.75–4.64 (m, 2H),
4.28–4.23 (m, 1H), 4.16–4.11 (m, 2H), 3.97–3.95 (m, 1H), 3.81–
3.79 (m, 2H), 3.43 (d, J = 2.0 Hz, 3H), 3.21 (d, J = 6.4 Hz, 3H),
1.65 (d, J = 7.2 Hz, 3H), 1.27 (d, J = 7.2 Hz, 3H), 1.07 (t, J = 6.8
Hz, 3H); 13C NMR (75 MHz, DMSO-d6): δ 172.0, 169.7, 169.0,
161.8, 154.6, 151.1, 150.6, 148.2, 141.8, 139.6, 125.6, 106.2,
101.5, 90.2, 81.8, 72.3, 70.5, 57.9, 54.6, 51.4, 48.1, 35.9, 29.6,
7(6H)-yl)acetate (31). White solid; Yield 50%; mp: compound
melting starts at 78oC and completely melts at 88oC; IR (KBr):
υmax/ cm-1 = 3444, 3124, 2986, 2943, 2836, 1756, 1704, 1662,
1553, 1457, 1398, 1377, 1268, 1229, 1202, 1132, 1077, 1029,
1
978, 812, 763, 749; H NMR (400 MHz, DMSO-d6): δ 8.20 (s,
1H), 8.05 (s, 1H), 7.50 (d, J = 8.4 Hz, 1H), 5.83 (d, J = 4.4 Hz,
1H), 5.75 (d, J = 7.6 Hz, 1H), 5.25 (s, 2H), 5.21 (s, 2H), 4.75 (d,
J = 5.6 Hz, 2H), 4.29 (q, J = 5.2 Hz, 1H), 4.13 (t, J = 4.4 Hz,
1H), 3.87 (t, J = 5.6 Hz, 1H), 3.80 (q, J = 7.2 Hz, 2H), 3.44 (s,
3H), 3.37 (s, 3H), 3.33 (s, 3H), 3.19 (s, 3H), 1.08 (t, J = 6.8 Hz,
3H); 13C NMR (75 MHz, DMSO-d6): δ 164.9, 160.8, 155.9,
27.7, 18.7, 18.0, 16.7, 12.7; HRMS
(ESI):
calcd
for
C27H34N10O10Na [M+Na]+: 681.2357, found: 681.2353; m/z
(ES)+: 659.34 [M+H]+.
151.2,148.2, 145.0, 143.9, 141.7, 127.0, 123.3, 105.7, 91.8, 85.0,
+
81H.7R, M71S.2(,E6S2I).:3,ca5l9cd.1f,o5r6C.0,H50N.0, O47.N9,a3[M7.9+,N2a9].9:,68217..293, 5173,.8fo;und: 681.2
27 34 10 10
4.6.2. (1-((5-(3-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-
3,4-dihydroxytetrahydrofuran-2-yl)methyl)-1H-1,2,3-triazol-4-
HRMS (ESI): calcd for C25H32N9O9 [M+H]+: 602.2323, found:
602.2329; m/z (ES)+: 602.31 [M+H]+.
yl)methyl
2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-
7(6H)-yl)propanoate (28). White solid; Yield 56%; mp:
compound melting starts at 78oC and completely melts at 90oC;
IR (KBr): υmax/ cm-1 = 3426, 3140, 2952, 1749, 1703, 1661, 1547,
4.6.6. (1-((5-(3-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-
3,4-dimethoxytetrahydro furan-2-yl)methyl)-1H-1,2,3-triazol-4-
yl)methyl
2-(2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-
1
1461, 1348, 1269, 1233, 1197, 1098, 1052, 810, 764, 749; H
7(6H)-yl)acetamido)acetate (32). White solid; Yield 43%; mp:
compound melting starts at 118oC and completely melts at
124oC; IR (KBr): υmax/ cm-1 = 3444, 3277, 3108, 2987, 2942,
2837, 1758, 1698, 1663, 1552, 1458, 1398, 1376, 1267, 1230,
1193, 1132, 1088, 1037, 975, 812, 764, 749; 1H NMR (400 MHz,
DMSO-d6): δ 8.70 (t, J = 5.6 Hz, 1H), 8.18 (s, 1H), 8.01 (s, 1H),
7.50 (d, J = 8.4 Hz, 1H), 5.82 (d, J = 4.4 Hz, 1H), 5.76 (d, J = 8.0
Hz, 1H), 5.17 (s, 2H), 5.05 (s, 2H), 4.74 (d, J = 4.8 Hz, 2H), 4.29
(q, J = 5.6 Hz, 1H), 4.13 (t, J = 4.4 Hz, 1H), 3.91 (d, J = 5.2 Hz,
2H), 3.86 (t, J = 5.2 Hz, 1H), 3.80 (q, J = 6.8 Hz, 2H), 3.43 (s,
3H), 3.37 (s, 3H), 3.33 (s, 3H), 3.19 (s, 3H), 1.08 (t, J = 7.2 Hz,
3H); 13C NMR (75 MHz, DMSO-d6): δ 171.7, 169.0, 161.9,
153.2, 151.5, 149.9, 148.3, 145.6, 143.3, 141.4, 126.8, 117.6,
106.2, 91.9, 84.0, 80.6, 71.0, 62.2, 59.3, 55.9, 50.0, 40.1, 29.8,
NMR (400 MHz, DMSO-d6): δ 8.18 (s, 1H), 8.10 (s, 1H), 7.53
(d, J = 8.0 Hz, 1H), 5.79–5.71 (m, 2H), 5.58 (q, J = 7.6 Hz, 1H),
5.52 (d, J = 6.0 Hz, 1H), 5.40 (d, J = 6.0 Hz, 1H), 5.21(s, 2H),
4.74–4.64 (m, 2H), 4.18–4.14 (m, 1H), 4.10–4.07 (m, 1H), 3.98–
3.95 (m, 1H), 3.81(q, J = 6.8 Hz, 2H), 3.43 (s, 3H), 3.18 (s, 3H),
1.73 (d, J = 6.8 Hz, 3H), 1.07 (t, J = 7.2 Hz, 3H); 13C NMR (75
MHz, DMSO-d6): δ 170.1, 166.6, 155.9, 151.8, 149.9, 144.1,
142.7, 123.8, 116.1, 104.9, 102.3, 88.6, 82.3, 78.0, 70.9, 56.3,
49.2, 46.7, 29.9, 27.9, 19.0, 14.2; HRMS (ESI): calcd for
C24H30N9O9 [M+H]+: 588.2166, found: 588.2161; m/z (ES)+:
588.5 [M+H]+.
4.6.3. (1-((5-(3-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-
3,4-dihydroxytetrahydrofuran-2-yl)methyl)-1H-1,2,3-triazol-4-