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L. Kalachova et al.
PAPER
jected into the reaction mixture and the resulting mixture was stirred
at 75 °C for 2 h. The solvent was then evaporated in vacuo. Products
were directly purified by flash chromatography on reverse phase us-
ing H2O–MeOH (0 to 100%) as an eluent.
139.58 (CH-4¢¢), 145.79 (CH-6), 149.68 (CH-6¢¢¢), 151.46 (CH-6¢¢),
153.57 (C-2), 154.11 (C-2¢¢), 154.69 (C-2¢¢¢), 163.93 (C-4).
MS (ESI): m/z (%) = 405 (3, [M+]), 428 (16, [M+ + Na]), 833 (100,
[2 M+ + Na]).
HRMS-ESI: m/z [M+ + H] calcd for C21H20N5O4: 406.1510; found:
406.1512.
5-[(2,2¢-Bipyridin-6-yl)ethynyl]-2¢-deoxycytidine (5a)
Prepared from deoxycytidine 3 and bipyridinyl acetylene 1a. It was
isolated as a brown powder in a yield of 70% (35 mg), which was
then crystallized from a mixture of MeOH–H2O; mp 139–146 °C.
Anal. Calcd for C21H19N5O4·0.5H2O: C, 60.86; H, 4.86; N, 16.90;
Found C, 61.13; H, 4.67; N, 16.60.
IR (KBr): 3392, 1645, 1500, 1094, 780 cm–1.
5-[(2,2¢:6¢,2¢¢-Terpyridin-4¢-yl)ethynyl]-2¢-deoxycytidine (5c)
Prepared from deoxycytidine 3 and terpyridinyl acetylene 1c. It was
isolated as a slightly brownish powder in a yield of 63% (38 mg),
which was then crystallized from a mixture of DMSO–H2O; mp
284–295 °C.
1H NMR (500 MHz, DMSO-d6): d = 2.07 (ddd, Jgem = 13.2 Hz,
J2¢b,1¢ = 7.0 Hz, J2¢b,3¢ = 6.1 Hz, 1 H, H-2¢b), 2.19 (ddd, Jgem = 13.2
Hz, J2¢a,1¢ = 6.1 Hz, J2¢a,3¢ = 3.7 Hz, 1 H, H-2¢a), 3.59 (ddd,
Jgem = 11.9 Hz, J5¢b,OH = 5.1 Hz, J5¢b,4¢ = 3.7 Hz, 1 H, H-5¢b), 3.67
(ddd, Jgem = 11.9 Hz, J5¢a,OH = 5.1 Hz, J5¢a,4¢ = 3.5 Hz, 1 H, H-5¢a),
3.82 (ddd, J4¢,5¢ = 3.7, 3.5 Hz, J4¢,3¢ = 3.3 Hz, 1 H, H-4¢), 4.24 (dddd,
IR (KBr): 3422, 2214, 1645, 1602, 1583, 1567, 1502, 1468, 1393,
1264, 1097, 792 cm–1.
J
J
3¢,2¢ = 6.1, 3.7 Hz, J3¢,OH = 4.3 Hz, J3¢,4¢ = 3.3 Hz, 1 H, H-3¢), 5.17 (t,
OH,5¢ = 5.1 Hz, 1 H, OH-5¢), 5.26 (d, J3¢,OH = 4.3 Hz, 1 H, OH-3¢),
1H NMR (500 MHz, DMSO-d6): d = 2.09 (dt, Jgem = 13.1 Hz,
6.15 (dd, J1¢,2¢ = 7.0, 6.1 Hz, 1 H, H-1¢), 7.17 (br s, 1 H, NHaHb), 7.49
(ddd, J5¢¢¢4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.7 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢),
7.87 (dd, J5¢¢4¢¢ = 7.7 Hz, J5¢¢3¢¢ = 1.1 Hz, 1 H, H-5¢¢), 7.90 (br s, 1 H,
NHaHb), 7.97 (ddd, J4¢¢¢,3¢¢¢ = 8.0 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz,
1 H, H-4¢¢¢), 8.00 (dd, J4¢¢,3¢¢ = 8.0 Hz, J4¢¢,5¢¢ = 7.7 Hz, 1 H, H-4¢¢),
8.36 (dd, J3¢¢,4¢¢ = 8.0 Hz, J3¢¢,5¢¢ = 1.1 Hz, 1 H, H-3¢¢), 8.38 (ddd,
J
J
2¢b,1¢ = J2¢b,3¢ = 6.4 Hz, 1 H, H-2¢b), 2.21 (ddd, Jgem = 13.1 Hz,
2¢a,1¢ = 5.9 Hz, J2¢a,3¢ = 3.6 Hz, 1 H, H-2¢a), 3.62 (ddd, Jgem = 11.9
Hz, J5¢b,OH = 4.9 Hz, J5¢b,4¢ = 3.9 Hz, 1 H, H-5¢b), 3.70 (ddd,
Jgem = 11.9 Hz, J5¢a,OH = 5.4 Hz, J5¢a,4¢ = 3.7 Hz, 1 H, H-5¢a), 3.83
(ddd, J4¢,5¢ = 3.9, 3.7 Hz, J4¢,3¢ = 3.1 Hz, 1 H, H-4¢), 4.26 (m,
J3¢,2¢ = 6.4, 3.6 Hz, J3¢,OH = 4.3 Hz, J3¢,4¢ = 3.1 Hz, 1 H, H-3¢), 5.19
J3¢¢¢,4¢¢¢ = 8.0 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 1.0 Hz, 1 H, H-3¢¢¢), 8.43 (s,
(dd, JOH,5¢ = 5.4, 4.9 Hz, 1 H, OH-5¢), 5.24 (d, J3¢,OH = 4.3 Hz, 1 H,
OH-3¢), 6.15 (dd, J1¢,2¢ = 6.4, 5.9 Hz, 1 H, H-1¢), 7.52 (br s, 1 H,
NHaHb), 7.53 (ddd, J5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.7 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz,
2 H, H-5¢¢¢), 7.82 (br s, 1 H, NHaHb), 8.03 (ddd, J4¢¢¢,3¢¢¢ = 8.0 Hz,
1 H, H-6), 8.71 (ddd, J6¢¢¢,5¢¢¢ = 4.7 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz, J6¢¢¢,3¢¢¢ = 1.0
Hz, 1 H, H-6¢¢¢).
13C NMR (125.7 MHz, DMSO-d6): d = 41.10 (CH2-2¢), 61.13 (CH2-
5¢), 70.21 (CH-3¢), 81.62 (C5-C≡C–C6¢¢), 85.76 (CH-1¢), 87.75
(CH-4¢), 88.79 (C-5), 93.86 (C5–C≡C–C6¢¢), 120.10 (CH-3¢¢),
120.90 (CH-3¢¢¢), 124.79 (CH-5¢¢¢), 128.05 (CH-5¢¢), 137.67 (CH-
4¢¢¢), 137.95 (CH-4¢¢), 142.42 (C-6¢¢), 146.22 (CH-6), 149.61 (CH-
6¢¢¢), 153.53 (C-2), 154.72 (C-2¢¢¢), 155.70 (C-2¢¢), 164.05 (C-4).
MS (ESI): m/z (%) = 428 (15, [M+ + Na]), 833 (100, [2 M+ + Na]).
HRMS-ESI: m/z [M+ + H] calcd for C21H20N5O4: 406.1510; found:
J
4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 2 H, H-4¢¢¢), 8.49 (s, 1 H, H-6), 8.62
(s, 2 H, H-3¢¢,5¢¢), 8.63 (ddd, J3¢¢¢,4¢¢¢ = 8.0 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz,
J
3¢¢¢,6¢¢¢ = 0.9 Hz, 2 H, H-3¢¢¢), 8.74 (ddd, J6¢¢¢,5¢¢¢ = 4.7 Hz, J6¢¢¢,4¢¢¢ = 1.8
Hz, J6¢¢¢,3¢¢¢ = 0.9 Hz, 2 H, H-6¢¢¢).
13C NMR (125.7 MHz, DMSO-d6): d = 41.02 (CH2-2¢), 61.09 (CH2-
5¢), 70.10 (CH-3¢), 85.78 (CH-1¢), 87.27 (C5–C≡C–C4¢¢), 87.75
(CH-4¢), 88.85 (C-5), 92.15 (C5–C≡C–C4¢¢), 121.10 (CH-3¢¢¢),
121.99 (CH-3¢¢,5¢¢), 124.89 (CH-5¢¢¢), 133.13 (C-4¢¢), 137.74 (CH-
4¢¢¢), 146.85 (CH-6), 149.51 (CH-6¢¢¢), 153.52 (C-2), 154.78 (C-
2¢¢¢), 155.30 (C-2¢¢,6¢¢), 163.93 (C-4).
406.1514.
Anal. Calcd for C21H19N5O4·1H2O·1MeOH: C, 58.01; H, 5.53; N,
15.38. Found: C, 57.97; H, 5.13; N, 15.20.
MS (ESI): m/z (%) = 483 (37, [M+ + H]), 505 (100, [M+ + Na]), 982
(86, [2 M+ + Na]).
5-[(2,2¢-Bipyridin-5-yl)ethynyl]-2¢-deoxycytidine (5b)
HRMS-ESI: m/z [M + H]+ calcd for C26H23N6O4: 483.1775; found:
483.1780.
Prepared from deoxycytidine 3 and bipyridinyl acetylene 1b. It was
isolated as a slightly yellow powder in a yield of 67% (34 mg), and
was then crystallized from a mixture of EtOH–H2O; mp >300 °C.
5-[(2,2¢-Bipyridin-6-yl)ethynyl]-2¢-deoxyuridine (6a)
IR (KBr): 3448, 1656, 1634, 1501, 1462, 1101, 794, 781, 742 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 2.05 (dt, Jgem = 13.3 Hz,
Prepared from deoxyuridine 4 and bipyridinyl acetylene 1a. Product
was isolated as yellow crystals in a yield of 75% (38 mg) and crys-
tallized from a mixture of MeOH–H2O; mp 129–136 °C.
J
J
2¢b,1¢ = J2¢b,3¢ = 6.4 Hz, 1 H, H-2¢b), 2.20 (ddd, Jgem = 13.3 Hz,
2¢a,1¢ = 6.1 Hz, J2¢a,3¢ = 3.9 Hz, 1 H, H-2¢a), 3.60 and 3.68 (2 br dt,
IR (KBr): 3424, 3061, 1699, 1626, 1454, 1429, 1274, 1094, 1056,
778 cm–1.
Jgem = 11.9 Hz, J5¢,OH = J5¢,4¢ = 3.5 Hz, 2 H, H-5¢), 3.82 (q,
J4¢,5¢ = J4¢,3¢ = 3.5 Hz, 1 H, H-4¢), 4.25 (br m, J3¢,2¢ = 6.4, 3.9 Hz,
1H NMR (500 MHz, DMSO-d6): d = 2.17 (ddd, Jgem = 13.3 Hz,
J3¢,OH = 4.3 Hz, J3¢,4¢ = 3.5 Hz, 1 H, H-3¢), 5.17 (br t, JOH,5¢ = 3.5 Hz,
1 H, OH-5¢), 5.26 (br d, J3¢,OH = 4.3 Hz, 1 H, OH-3¢), 6.13 (dd,
J2¢b,1¢ = 6.2 Hz, J2¢b,3¢ = 3.9 Hz, 1 H, H-2¢b), 2.21 (ddd, Jgem = 13.3
Hz, J2¢a,1¢ = 6.9 Hz, J2¢a,3¢ = 5.9 Hz, 1 H, H-2¢a), 3.60 (ddd,
Jgem = 12.1 Hz, J5¢b,OH = 4.5 Hz, J5¢b,4¢ = 3.6 Hz, 1 H, H-5¢b), 3.68
(ddd, Jgem = 12.1 Hz, J5¢a,OH = 4.8 Hz, J5¢a,4¢ = 3.6 Hz, 1 H, H-5¢a),
3.83 (td, J4¢,5¢ = 3.6 Hz, J4¢,3¢ = 3.0 Hz, 1 H, H-4¢), 4.27 (m,
J
J
1¢,2¢ = 6.4, 6.1 Hz, 1 H, H-1¢), 7.21 (br s, 1 H, NHaHb), 7.47 (ddd,
5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.8 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢), 7.85
(br s, 1 H, NHaHb), 7.97 (ddd, J4¢¢¢,3¢¢¢ = 7.9 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz,
J4¢¢¢,6¢¢¢ = 1.8 Hz, 1 H, H-4¢¢¢), 8.14 (dd, J4¢¢,3¢¢ = 8.3 Hz, J4¢¢,6¢¢ = 2.1 Hz,
J
3¢,2¢ = 5.9, 3.9 Hz, J3¢,OH = 4.3 Hz, J3¢,4¢ = 3.0 Hz, 1 H, H-3¢), 5.21 (br
1 H, H-4¢¢), 8.40 (ddd, J3¢¢¢,4¢¢¢ = 7.9 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 1.0
Hz, 1 H, H-3¢¢¢), 8.41 (dd, J3¢¢,4¢¢ = 8.4 Hz, J3¢¢,6¢¢ = 0.9 Hz, 1 H, H-3¢¢),
8.42 (s, 1 H, H-6), 8.70 (ddd, J6¢¢¢,5¢¢¢ = 4.8 Hz, J6¢¢¢,4¢¢¢ = 1.8 Hz,
dd, JOH,5¢ = 4.8, 4.5 Hz, 1 H, OH-5¢), 5.30 (br d, J3¢,OH = 4.3 Hz, 1 H,
OH-3¢), 6.14 (dd, J1¢,2¢ = 6.9, 6.2 Hz, 1 H, H-1¢), 7.49 (ddd,
J
5¢¢¢,4¢¢¢ = 7.5 Hz, J5¢¢¢,6¢¢¢ = 4.8 Hz, J5¢¢¢,3¢¢¢ = 1.2 Hz, 1 H, H-5¢¢¢), 7.61
(dd, J5¢¢,4¢¢ = 7.7 Hz, J5¢¢,3¢¢ = 1.0 Hz, 1 H, H-5¢¢), 7.97 (ddd,
4¢¢¢,3¢¢¢ = 8.0 Hz, J4¢¢¢,5¢¢¢ = 7.5 Hz, J4¢¢¢,6¢¢¢ = 1.8 Hz, 1 H, H-4¢¢¢), 7.99
(dd, J4¢¢,3¢¢ = 8.0 Hz, J4¢¢,5¢¢ = 7.7 Hz, 1 H, H-4¢¢), 8.36 (ddd,
3¢¢¢,4¢¢¢ = 8.0 Hz, J3¢¢¢,5¢¢¢ = 1.2 Hz, J3¢¢¢,6¢¢¢ = 1.0 Hz, 1 H, H-3¢¢¢), 8.37
(dd, J3¢¢,4¢¢ = 8.0 Hz, J3¢¢,5¢¢ = 1.0 Hz, 1 H, H-3¢¢), 8.50 (s, 1 H, H-6),
J
6¢¢¢,3¢¢¢ = 1.0 Hz, 1 H, H-6¢¢¢), 8.88 (dd, J6¢¢,4¢¢ = 2.1 Hz, J6¢¢,3¢¢ = 0.9 Hz,
1 H, H-6¢¢).
J
13C NMR (125.7 MHz, DMSO-d6): d = 41.12 (CH2-2¢), 61.06 (CH2-
5¢), 70.09 (CH-3¢), 85.77 (CH-1¢), 86.36 (C5–C≡C–C5¢¢)), 87.70
(CH-4¢), 89.22 (C-5), 91.18 (C5–C≡C–C5¢¢), 120.05 (CH-3¢¢),
120.09 (C-5¢¢), 121.00 (CH-3¢¢¢), 124.71 (CH-5¢¢¢), 137.68 (CH-4¢¢¢),
J
Synthesis 2009, No. 1, 105–112 © Thieme Stuttgart · New York