3¢-Benzylamino-3¢-deoxy-5¢-O-triphenylmethyl-b-D-thymidine 5a
2), 163.67 (C-4). HRMS (ESI-MS) for C37H34ClF3N3O4 [M+H]+
found, 676.2194; calcd, 676.2184.
Reaction of compound 4 (88 mg, 0.18 mmol), benzaldehyde
(17 mL, 0.17 mmol) in 0.7 mL MeOH was performed as
described in the general synthesis of 3¢-benzylamino-3¢-deoxy-
5¢-O-triphenylmethyl-b-D-thymidine analogues affording 5a as a
3¢-Benzylamino-3¢-deoxy-b-D-thymidine 6a
1
colourless solid (17 mg, 16%). H NMR (300 MHz, CDCl3): d
Compound 5a (94 mg, 0.16 mmol) was dissolved in a mixture of
ZnBr2 (592 mg, 2.63 mmol) in CH2Cl2/iPrOH (2.6 mL, 85 : 15) and
stirred overnight at room temperature. The reaction was quenched
with water and extracted with CH2Cl2 (3 ¥ 5 mL). The combined
organic layers were dried over MgSO4 and evaporated to dryness.
The resulting residue was purified by column chromatography
(CH2Cl2–MeOH 95 : 5), to yield 6a (18.2 mg, 34%) as a colourless
oil. 1H NMR (300 MHz, DMSO-d6): d 1.77 (3H, m, 5-CH3), 1.99–
2.14 (2H, m, H-2¢a and H-2¢b), 3.27–3.33 (1H, m, H-3¢), 3.53–3.71
(4H, m, H-5¢a, H-5¢b and CH2Ph), 3.76–3.80 (1H, m, H-4¢), 4.10
(1H, app br s, 3¢-NH), 5.01 (1H, br s, 5¢-OH), 6.15 (1H, app t, J =
6.3 Hz, H-1¢), 7.19–7.32 (5H, m, CH2Ph), 7.74 (1H, d, J = 1.2 Hz,
H-6), 11.25 (1H, s, 3-NH). 13C NMR (75 MHz, DMSO-d6): d 12.27
(5-CH3), 37.55 (C-2¢), 51.10 (CH2Ph), 57.39 (C-3¢), 61.75 (C-5¢),
83.96 (C-1¢), 85.32 (C-4¢), 109.14 (C-5), 126.56, 127.96 and 128.09
(CH2Ph), 136.25 (C-6), 140.78 (CH2Ph), 150.42 (C-2), 163.77 (C-
4). HRMS (ESI-MS) for C17H22N3O4 [M+H]+ found, 332.1613;
calcd, 332.1605.
1.47 (3H, d, J = 1.2 Hz, 5-CH3), 2.29 (2H, app t, J = 6.0 Hz, H-2¢a
and H-2¢b), 3.33–3.47 (2H, m, H-5¢a and H-5¢b), 3.57 (1H, app
dd, J = 6.3 Hz, J = 12.3 Hz, H-3¢), 3.74 (2H, app q, J = 13.2 Hz,
CH2Ph), 3.91–3.93 (1H, m, H-4¢), 6.26 (1H, app t, J = 6.0 Hz,
H-1¢), 7.20–7.40 (20H, m, Tr and CH2Ph), 7.52 (1H, d, J = 0.9 Hz,
H-6). 13C NMR (75 MHz, CDCl3): d 12.10 (5-CH3), 39.60 (C-2¢),
52.29 (CH2Ph), 57.53 (C-3¢), 63.80 (C-5¢), 84.68 (C-1¢), 85.11 (C-
4¢), 87.45 (Tr), 110.96 (C-5), 127.42, 127.51, 128.15, 128.71, 128.81
(CH2Ph and Tr), 135.70 (C-6), 139.60 (CH2Ph), 143.50 (Tr), 150.29
(C-2), 163.77 (C-4). HRMS (ESI-MS) for C36H36N3O4 [M+H]+
found, 574.2770; calcd, 574.2700.
3¢-(4-Chlorobenzylamino)-3¢-deoxy-5¢-O-triphenylmethyl-b-D-
thymidine 5b
Reaction of compound
4
(82 mg, 0.17 mmol), 4-
chlorobenzaldehyde (23 mg, 0.16 mmol) in 0.6 mL MeOH
was performed as described in the general synthesis of 3¢-
benzylamino-3¢-deoxy-5¢-O-triphenylmethyl-b-D-thymidine ana-
logues affording 5b as a colourless solid (91 mg, 88%). 1H NMR
(300 MHz, DMSO-d6): d 1.43 (3H, d, J = 0.9 Hz, 5-CH3),
2.13–2.27 (2H, m, H-2¢a and H-2¢b), 3.16-3.24 (2H, m, H-5¢a
and H-5¢b), 3.39 (1H, app dt, J = 5.7 Hz, H-3¢), 3.67 (2H, app q,
J = 14.1 Hz, CH2Ph), 3.87–3.91 (1H, m, H-4¢), 6.19 (1H, app t,
J = 6.3 Hz, H-1¢), 7.24–7.37 (19H, m, Tr and CH2Ph), 7.51 (1H,
d, J = 0.9 Hz, H-6), 11.32 (1H, s, 3-NH). 13C NMR (75 MHz,
DMSO-d6): d 11.75 (5-CH3), 37.44 (C-2¢), 49.98 (CH2Ph), 56.83
(C-3¢), 64.04 (C-5¢), 83.26 (C-1¢), 83.91 (C-4¢), 86.30 (Tr), 109.38
(C-5), 127.14, 127.93, 128.01, 128.24, 129.70, 131.06 (Tr and
CH2Ph), 135.66 (C-6), 139.60 (CH2Ph), 143.48 (Tr), 150.34 (C-2),
163.67 (C-4). HRMS (ESI-MS) for C36H35ClN3O4 [M+H]+ found,
608.2357; calcd, 608.2311.
3¢-(4-Chlorobenzylamino)-3¢-deoxy-b-D-thymidine 6b
Compound 6b (14 mg, 56%, colourless solid) was synthesized from
5b (40 mg, 0.066 mmol) using the same procedure as was described
1
for the synthesis of 6a. H NMR (300 MHz, DMSO-d6): d 1.76
(3H, d, J = 1.0 Hz, 5-CH3), 2.04-2.10 (2H, m, H-2¢a and H-2¢b),
3.24–3.40 (1H, m, H-3¢), 3.51–3.66 (2H, m, H-5¢a and H-5¢b), 3.69
(2H, d, J = 3.3 Hz, CH2Ph), 3.75–3.79 (1H, m, H-4¢), 5.02 (1H,
br s, 5¢-OH), 6.14 (1H, app t, J = 6.5 Hz, H-1¢), 7.37 (4H, app s,
CH2Ph), 7.73 (1H, d, J = 1.3 Hz, H-6), 11.25 (1H, s, 3-NH). 13C
NMR (75 MHz, DMSO-d6): d 12.35 (5-CH3), 37.58 (C-2¢), 50.30
(CH2Ph), 57.33 (C-3¢), 61.77 (C-5¢), 84.03 (C-1¢), 85.35 (C-4¢),
109.27 (C-5), 128.12, 129.88 and 131.12 (CH2Ph), 136.35 (C-6),
139.95 (CH2Ph), 150.51 (C-2), 163.90 (C-4). HRMS (ESI-MS) for
C17H21ClN3O4 [M+H]+ found, 366.1215; calcd, 366.1215.
3¢-[(3-Trifluoromethyl-4-chloro)-benzylamino]-3¢-deoxy-5¢-O-
triphenylmethyl-b-D-thymidine 5c
3¢-[(3-Trifluoromethyl-4-chloro)-benzylamino]-3¢-deoxy-b-D-
thymidine 6c
Reaction of compound 4 (108 mg, 0.22 mmol), 4-chloro-3-
(trifluoromethyl)benzaldehyde (51 mg, 0.24 mmol) in 0.8 mL
MeOH was performed as described in the general synthesis
of 3¢-benzylamino-3¢-deoxy-5¢-O-triphenylmethyl-b-D-thymidine
Compound 6c (80 mg, 58%, colourless solid) was synthesized
from 5c (97 mg, 0.14 mmol) using the same procedure as was
1
1
analogues affording 5c as a colourless solid (103 mg, 68%). H
described for the synthesis of 6a. H NMR (300 MHz, DMSO-
NMR (300 MHz, DMSO-d6): d 1.44 (3H, d, J = 0.9 Hz, 5-CH3),
2.18-2.26 (2H, m, H-2¢a and H-2¢b), 3.19 (2H, d, J = 3.6 Hz, H-
5¢a and H-5¢b), 3.30–3.38 (1H, m, H-3¢), 3.74 (2H, app q, J =
14.1 Hz, CH2Ph), 3.88–3.89 (1H, m, H-4¢), 6.18 (1H, app t, J =
6.6 Hz, H-1¢), 7.24–7.34 (15H, m, Tr), 7.50 (1H, d, J = 1.5 Hz,
H-6), 7.55–7.63 (2H, m, CH2Ph), 7.76 (1H, d, J = 1.5 Hz, CH2Ph),
11.31 (1H, s, 3-NH). 13C NMR (75 MHz, DMSO-d6): d 11.79
(5-CH3), 37.29 (C-2¢), 49.49 (CH2Ph), 57.09 (C-3¢), 59.74 (C-5¢),
83.22 (C-1¢), 83.87 (C-4¢), 86.28 (Tr), 109.38 (C-5), 121.15, 124.77,
126.93–128.22, 128.63 (Tr and CH2Ph), 131.28 (CH2Ph), 133.47
(CH2Ph), 135.70 (C-6), 140.99 (CH2Ph), 143.49 (Tr), 150.34 (C-
d6): d 1.77 (3H, d, J = 1.2 Hz, 5-CH3), 2.05–2.12 (2H, m, H-2¢a
and H-2¢b), 3.25–3.33 (1H, m, H-3¢), 3.52–3.67 (2H, m, H-5¢a,
H-5¢b), 3.73–3.84 (3H, m, H-4¢ and CH2Ph), 4.07 (1H, app br s,
3¢-NH), 5.01 (1H, br s, 5¢-OH), 6.15 (1H, app t, J = 6.3 Hz, H-
1¢), 7.67 (2H, app s, CH2Ph), 7.73 (1H, d, J = 0.9 Hz, H-6), 7.84
(1H, app s, CH2Ph), 11.25 (1H, s, 3-NH). 13C NMR (75 MHz,
DMSO-d6): d 12.25 (5-CH3), 37.43 (C-2¢), 49.63 (CH2Ph), 57.24
(C-3¢), 61.62 (C-5¢), 83.88 (C-1¢), 85.22 (C-4¢), 109.15 (C-5), 124.83,
126.06–128.57, 131.30 and 133.59 (CF3 and CH2Ph), 136.21 (C-6),
141.23 (CH2Ph), 150.41 (C-2), 163.76 (C-4). HRMS (ESI-MS) for
C18H20ClF3N3O4 [M+H]+ found, 434.1114; calcd, 434.1089.
896 | Org. Biomol. Chem., 2011, 9, 892–901
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