978
P. Van Rompaey et al. / Bioorg. Med. Chem. 13 (2005) 973–983
evaporated in vacuo. Precipitation from MeOH and
subsequent filtration for 3–6 or purification by silica
gel chromatography (CH2Cl2–MeOH) for 24–26, 30
and 31 furnished the desired product as a white pure
solid.
3.45 (dd, 1H, J = 5.7 Hz and ꢀ12.3 Hz, 30-CHb), 3.55
(ddd, 1H, J = 3.7 Hz, 5.4 Hz and ꢀ12.2 Hz, H-5B0),
3.65 (dd, 1H, J = 8.1 Hz, 30-CHa), 3.75 (ddd, 1H,
J = 2.9 Hz and 5.0 Hz, H-5A0), 3.83 (s, 3H, Ar–
OCH3), 4.01 (dt, 1H, J = 3.2 Hz and 8.7 Hz, H-40),
4.63 (m, 3H, H-20 and N6–CH2–Ar), 5.16 (t, 1H,
J = 5.4 Hz, 50-OH), 5.95 (d, 1H, J = 2.1 Hz, H-10), 6.01
(d, 1H, J = 5.0 Hz, 20-OH), 7.01 (d, 1H, J = 8.8 Hz,
Ar–H-3), 7.08 (br s, 1H, Ar–H-6), 7.24 (dd, 1H,
J = 2.6 and 8.8 Hz, Ar–H-4), 8.19 (br s, 2H, H-2 and
N6–H), 8.44 (s, 1H, H-8); exact mass (ESI-MS) calcu-
lated for C19H22ClN8O4 [M+H]+: 461.1452, found
461.1460. Anal. (C19H21ClN8O4) C , H, N.
4.3. 9-(3-C-Azidomethyl-3-deoxy-b-D-ribofuranosyl)-ade-
nine (3)
Compound 2 (300 mg, 0.62 mmol) yielded 80 mg (42%)
1
of 3: H NMR (DMSO-d6) d 2.58–2.67 (m, 1H, H-30),
3.44 (dd, 1H, J = 5.7 Hz and ꢀ12.4 Hz, 30-CHb), 3.53
(ddd, 1H, J = 3.8 Hz and 5.9 Hz and ꢀ12.2 Hz, H-5B0),
3.65 (dd, 1H, J = 8.2 Hz, 30-CHa), 3.73 (ddd, 1H,
J = 3.0 Hz and 5.1 Hz, H-5A0), 3.99 (dt, 1H, J = 3.2 Hz
and 8.6 Hz, H-40), 4.54–4.58 (m, 1H, H-20), 5.22 (t, 1H,
J = 5.5 Hz, 50-OH), 5.91 (d, 1H, J = 2.1 Hz, H-10), 6.04
(d, 1H, J = 4.6 Hz, 20-OH), 7.29 (s, 2H, 6-NH2), 8.13
and 8.39 (2s, 2H, H-2 and H-8); exact mass (ESI-MS)
calculated for C11H15N8O3 [M+H]+: 307.1267, found
307.1270. Anal. (C11H14N8O3Æ1/4H2O) C, H, N.
4.7. 9-[3-Azido-3-deoxy-5-(methylcarbamoyl)-b-D-ribo-
furanosyl]-N6-(3-iodobenzyl) adenine (24)
Compound 21 (300 mg, 0.79 mmol) yielded 250 mg
(60%) of 24; spectroscopic data of this compound in
accordance with those reported in Ref. 40; Anal.
(C18H18IN9O3Æ3/2 H2O) C, H, N.
4.4. 9-(3-C-Azidomethyl-3-deoxy-b-D-ribofuranosyl)-N6-
methyladenine (4)
4.8. 9-[3-C-Azidomethyl-3-deoxy-5-(methylcarbamoyl)-b-
D-ribofuranosyl]-N6-(3-iodobenzyl)adenine (25)
Compound 2 (400 mg, 0.82 mmol) yielded 180 mg (68%)
Compound 22 (300 mg, 0.75 mmol) yielded 360 mg
(73%) of 25: 1H NMR (DMSO-d6) d 2.63 (d, 3H,
J = 4.4 Hz, CH3–N), 2.75–2.84 (m, 1H, H-30), 3.50
(dd, 1H, J = 5.9 Hz and ꢀ12.3 Hz, 30-CHb), 3.71 (dd,
1H, J = 7.9 Hz, 30-CHa), 4.33 (d, 1H, J = 8.5 Hz, H-
40), 4.63 (m, 3H, H-20 and N6–CH2–Ar), 6.03 (d, 1H,
J = 2.1 Hz, H-10), 6.15 (d, 1H, J = 4.7 Hz, 20-OH), 7.09
(t, 1H, J = 7.8 Hz, Ar–H-5), 7.35 (d, 1H, J = 7.6 Hz,
Ar–H-6), 7.57 (d, 1H, J = 7.9 Hz, Ar–H-4), 7.71 (s,
1H, Ar–H-2), 8.24 (m, 2H, H-2 and NH–CO), 8.43 (br
s, 1H, N6–H), 8.55 (s, 1H, H-8); exact mass (ESI-MS)
calculated for C19H21IN9O3 [M+H]+: 550.0813, found
550.0803. Anal. (C19H20IN9O3Æ3/2H2O) C, H, N.
1
of 4: H NMR (DMSO-d6) d 2.58–2.68 (m, 1H, H-30),
2.93 (br s, 3H, N6–CH3), 3.44 (dd, 1H, J = 5.6 Hz and
ꢀ12.31 Hz, 30-CHb), 3.53 (ddd, 1H, J = 3.7 Hz, 5.7 Hz
and ꢀ12.2 Hz, H-5B0), 3.64 (dd, 1H, J = 7.9 Hz, 30-
CHa), 3.73 (ddd, 1H, J = 2.9 Hz and 5.3 Hz, H-5A0),
3.99 (dt, 1H, J = 3.2 Hz and 8.8 Hz, H-40), 4.55 (dt,
1H, J = 2.1 Hz and 5.2 Hz, H-20), 5.23 (t, 1H,
J = 5.4 Hz, 50-OH), 5.92 (d, 1H, J = 2.3 Hz, H-10), 6.05
(d, 1H, J = 5.0 Hz, 20-OH), 7.78 (s, 1H, N6–H), 8.22
and 8.39 (2s, 2H, H-2 and H-8); exact mass (ESI-MS)
calculated for C12H17N8O3 [M+H]+: 321.1423, found
321.1429. Anal. (C12H16N8O3Æ2/3H2O) C, H, N.
4.5. 9-(3-C-Azidomethyl-3-deoxy-b-D-ribofuranosyl)-N6-
(3-iodobenzyl)adenine (5)
4.9. 2-Chloro-9-[3-azido-3-deoxy-5-(methylcarbamoyl)-b-
D-ribofuranosyl]-N6-(3-iodobenzyl)adenine (26)
Compound 2 (340 mg, 0.69 mmol) yielded 227 mg (62%)
Compound 23 (200 mg, 0.48 mmol) yielded 210 mg
(77%) of 26: 1H NMR (DMSO-d6) d 2.69 (d, 3H,
J = 4.1 Hz, CH3–N), 4.35 (d, 1H, J = 2.9 Hz, H-40),
4.47 (t, 1H, J = 4.1 Hz, H-30), 4.60 (br s, 2H, N6–
CH2–Ar), 4.92 (app d, 1H, J = 4.9 Hz, H-20), 5.92 (d,
1H, J = 6.2 Hz, H-10), 6.31 (d, 1H, J = 4.7 Hz, 20-OH),
7.12 (t, 1H, J = 7.8 Hz, Ar–H-5), 7.35 (d, 1H,
J = 7.3 Hz, Ar–H-6), 7.59 (d, 1H, J = 7.9 Hz, Ar–H-4),
7.74 (s, 1H, Ar–H-2), 8.25 (d, 1H, J = 4.1 Hz, NH–
CO), 8.49 (s, 1H, H-8), 8.99 (br s, 1H, N6–H); exact mass
(ESI-MS) calculated for C18H17ClIN9O3Na [M+Na]+:
592.0087, found 592.0092. Anal. (C18H17ClIN9O3Æ
1/2H2O) C, H, N.
1
of 5: H NMR (DMSO-d6) d 2.59–2.68 (m, 1H, H-30),
3.44 (dd, 1H, J = 5.6 Hz and ꢀ12.3 Hz, 30-CHb), 3.54
(ddd, 1H, J = 3.7 Hz, 5.6 Hz and ꢀ12.3 Hz, H-5B0),
3.64 (dd, 1H, J = 8.2 Hz, 30-CHa), 3.73 (ddd, 1H,
J = 2.9 Hz and 5.3 Hz, H-5A0), 4.00 (dt, 1H, J = 3.2 Hz
and 8.6 Hz, H-40), 4.55–4.59 (m, 1H, H-20), 4.64 (br s,
2H, N6–CH2–Ar), 5.20 (t, 1H, J = 5.6 Hz, 50-OH), 5.93
(d, 1H, J = 2.1 Hz, H-10), 6.05 (d, 1H, J = 5.0 Hz, 20-
OH), 7.05 (t, 1H, J = 7.8 Hz, Ar–H-5), 7.34 (d, 1H,
J = 7.9 Hz, Ar–H-6), 7.56 (d, 1H, J = 8.2 Hz, Ar–H-4),
7.70 (s, 1H, Ar–H-2), 8.20 and 8.44 (2s, 2H, H-2 and
H-8), 8.46 (br s, 1H, N6–H); exact mass (ESI-MS) calcu-
lated for C18H20IN8O3 [M+H]+: 523.0704, found
523.0698. Anal. (C18H19IN8O3) C , H, N.
4.10. 9-[3-Azido-3-deoxy-5-(methylcarbamoyl)-b-D-ribo-
furanosyl]-N6-(5-chloro-2-methoxybenzyl)adenine (30)
4.6. 9-(3-C-Azidomethyl-3-deoxy-b-D-ribofuranosyl)-N6-
(5-chloro-2-methoxybenzyl) adenine (6)
Compound 21 (300 mg, 0.79 mmol) yielded 251 mg
(67%) of 30: 1H NMR (DMSO-d6) d 2.68 (d, 3H,
J = 4.7 Hz, CH3–N), 3.83 (s, 3H, Ar–OCH3), 4.34 (d,
1H, J = 3.2 Hz, H-40), 4.49 (dd, 1H, J = 3.2 Hz and
Compound 2 (300 mg, 0.62 mmol) yielded 100 mg (35%)
1
of 6: H NMR (DMSO-d6) d 2.61–2.70 (m, 1H, H-30),