N. Kojima et al. / Tetrahedron 56 (2000) 7909±7914
7913
5-[N-(tert-Butoxycarbonyl)]amino-1-(5-O-tert-butyldi-
methylsilyl-2,3-O-isopropylidene-b-d-ribofuranosyl)-
imidazole-4-(N-benzyl)carboxamide (7). To a solution of
3 (406 mg, 0.5 mmol) in dichloromethane (4 mL) was
added benzylamine (0.22 mL, 2.0 mmol), and the reaction
mixture was stirred for 24 h at room temperature. The
solvent was removed in vacuo, and the residue was puri®ed
by a silica gel column, eluted with hexane/AcOEt (5:1±1:1),
to give 7 (265 mg, 88% as a white foam): FAB-LRMS m/z
603 (MH1); FAB-HRMS calcd for C30H47N4O7Si 603.3213,
6-Cyano-5,7-dihydroxy-3-(5-O-tert-butyldimethylsilyl-2,3-
O-isopropylidene-b-d-ribofuranosyl)imidazo[4,5-b]pyri-
dine (10). A solution of 8 (300 mg, 0.56 mmol) in a mixture
of EtOH (10 mL), 5% aqueous Na2CO3 (5 mL) was heated
at 1008C for 2 h. The solvent was removed in vacuo, and
the residue was dissolved in H2O (50 mL). The solution was
neutralized with 1N HCl, and then activated charcoal was
added to the aqueous solution until no UV absorption
was observed in the supernatant. The solution including
the activated charcoal was poured into a glass tube, and
the activated charcoal was washed with H2O. The desired
10 was then eluted with a mixture of 28% ammonium
hydroxide/EtOH (3:7). The UV-absorbing fractions were
combined, and the solvent was removed to give 10
(233 mg, 91%, crystallized from AcOEt): mp .3008C;
1
found 603.3229. H NMR (CDCl3) 7.76 (br s, 1H, D2O
exchangeable), 7.57 (s, 1H), 7.31±7.23 (m, 6H), 6.11 (d,
1H, J2.3 Hz), 4.76 (m, 2H), 4.55 (m, 2H), 4.38 (m, 1H),
3.83 (dd, 1H, J3.0, 11.5 Hz), 3.73 (dd, 1H, J3.3,
11.5 Hz), 1.52 (s, 3H), 1.48 (s, 9H), 1.33 (s, 3H), 0.82 (s,
9H), 0.05 and 0.02 (each s, each 3H); 13C NMR (CDCl3)
163.42, 153.18, 138.42, 131.43, 129.96, 128.55, 127.59,
127.24, 113.63, 92.75, 86.67, 86.08, 81.78, 80.97, 63.42,
42.60, 28.06, 27.25, 25.83, 25.54, 18.25, 25.53, 25.67.
FAB-LRMS m/z 462 (M1); IR 2210 cm21 1H NMR
;
(DMSO-d6) 10.59 (br s, 1H, D2O exchangeable), 7.71 (s,
1H), 6.04 (d, 1H, J2.9 Hz), 5.17 (m, 1H), 4.89 (m, 1H),
4.09 (m, 1H), 3.65 (dd, 1H, J5.3, 11.2 Hz), 3.61 (dd, 1H,
J5.3, 11.2 Hz), 1.54 and 1.33 (each s, each 3H), 0.84 (s,
9H), 0.03 (s, 6H); 13C NMR (DMSO-d6) 173.03, 164.47,
134.06, 122.20, 120.94, 113.35, 87.72, 85.55, 83.16,
80.73, 79.49, 63.18, 26.86, 25.77, 25.31, 17.96, 25.47.
Anal. Calcd for C21H30N4O6Si´1/4H2O: C, 54.00; H, 6.58;
N, 11.99. Found: C, 53.82, H, 6.53; N, 12.14.
5-[N-(tert-Butoxycarbonyl)]amino-4-cyanoacetyl-1-(5-O-
tert-butyldimethylsilyl-2,3-O-isopropylidene-b-d-ribo-
furanosyl)imidazole (8) and 5-[N-(tert-butoxycarbonyl)]-
amino-1-(5-O-tert-butyldimethylsilyl-2,3-O-isopropyl-
idene-b-d-ribofuranosyl)imidazole-4-[N-(tert-butoxy-
carbonyl)]carboxamide (9). To a solution of acetonitrile
(1.5 mL, 28.5 mmol) in THF (70 mL) was added n-BuLi
(1.63 M in THF, 15.6 mL, 25.5 mmol) over 20 min at
2788C. To the resulting orange solution, a THF solution
(30 mL) of 3 (4.14 g, 5.1 mmol) was added dropwise, and
the whole was stirred for 1 h at the same temperature. The
reaction was quenched by addition of saturated aqueous
NH4Cl, and the reaction mixture was partitioned between
AcOEt and H2O. The separated organic layer was washed
with H2O, followed by brine. The organic layer was dried
(Na2SO4) and concentrated in vacuo. The residue was puri-
®ed by a silica gel column, eluted with hexane/AcOEt (5:1±
1:1), to give 8 (2.1 g, 76% as a white foam) and 9 (533 mg,
19% as a white foam).
5-Amino-4-cyanoacetyl-1-b-d-ribofuranosylimidazole
(11). A solution of 8 (2.73 g, 5.1 mmol) in 70% aqueous
TFA (60 mL) was sitrred for 12 h at room temperature.
The solvent was removed in vacuo, and the residue was
co-evaporated three times with EtOH. The residue was
puri®ed by a silica gel column, eluted with EtOH in
CHCl3 (0±30%), to give 11 (1.4 g, 96%, crystallized from
1
MeOH): mp 202±2038C; FAB-LRMS m/z 283 (MH1); H
NMR (DMSO-d6) 7.39 (s, 1H), 7.01 (br s, 2H, D2O
exchangeable), 5.54 (d, 1H, J6.7 Hz), 5.40 (d, 1H, J
6.4 Hz, D2O exchangeable), 5.36 (t, 1H, J4.9 Hz, D2O
exchangeable), 5.18 (d, 1H, J4.3 Hz, D2O exchangeable),
4.27 (ddd, 1H, J6.7, 6.4, 5.6 Hz), 4.13 (s, 2H), 4.04 (ddd,
1H, J5.6, 4.3, 2.5 Hz), 3.93 (m, 1H), 3.59 (m, 2H); 13C
NMR (DMSO-d6) 180.25, 146.84, 130.75, 118.32, 116.60,
87.50, 85.70, 72.76, 70.40, 61.10, 27.26. Anal. Calcd for
C11H14N4O5: C, 46.81; H, 5.00; N, 19.85. Found: C,
46.71, H, 5.05; N, 19.68.
Physical data for 8. FAB-LRMS m/z 537 (MH1); FAB-
HRMS calcd for C25H41N4O7Si 537.2744, found 537.2712.
IR 2260 cm21 1H NMR (CDCl3) 7.78 (br s, 1H, D2O
;
exchangeable), 7.66 (s, 1H), 6.15 (d, 1H, J1.8 Hz), 4.73
(m, 2H), 4.46 (m, 1H), 4.15 and 4.06 (each d, each 1H,
J19.6 Hz), 3.86 (dd, 1H, J2.5, 11.5 Hz), 3.75 (dd, 1H,
J2.8, 11.5 Hz), 1.54 (s, 3H), 1.51 (s, 9H), 1.36 (s, 3H),
0.82 (s, 9H), 0.04 and 0.02 (each s, each 3H); 13C NMR
(CDCl3) 183.94, 152.07, 132.99, 132.86, 127.35, 114.23,
113.72, 93.58, 87.07, 85.97, 82.70, 81.19, 63.53, 28.87,
27.98, 27.17, 25.76, 25.42, 18.20, 25.62, 25.76.
5-Amino-3-(b-d-ribufuranosyl)imidazo[4,5-b]pyridin-7-
one (1-deazaguanosine, 12). In the same manner as
described for 10, 11 (240 mg, 0.85 mmol) was heated in a
mixture of EtOH (10 mL), 5% aqueous Na2CO3 (5 mL) to
give 12 (155 mg, 65%, crystallized from EtOH): mp 144±
1468C (lit.17 mp 148±1508C); 1H NMR (DMSO-d6) 7.94 (s,
1H), 5.80 (s, 1H), 5.76 (d, 1H, J6.4 Hz), 5.56 (br s, 2H,
D2O exchangeable), 5.49 (br s, 1H, D2O exchangeable),
5.29 (br s, 1H, D2O exchangeable), 5.05 (br s, 1H, D2O
exchangeable), 5.52 (br t, 1H), 4.08 (br s, 1H), 3.89 (br s,
1H), 3.64 (dd, 1H, J3.5, 12.1 Hz), 3.53 (dd, 1H, J3.5,
12.1 Hz); 13C NMR (DMSO-d6) 157.99, 157.16, 147.11,
136.70, 119.06, 89.57, 87.15, 85.40, 72.99, 70.74, 61.80.
Physical data for 9. FAB-LRMS m/z 613 (MH1); FAB-
HRMS calcd for C28H49N4O9Si 613.3268, found 613.3268.
1H NMR (CDCl3) 8.79 (br s, 1H, D2O exchangeable), 7.70
(br s, 1H, D2O exchangeable), 7.60 (s, 1H), 6.10 (d, 1H,
J2.3 Hz), 4.75 (m, 2H), 4.40 (m, 1H), 3.83 (dd, 1H,
J2.3, 11.2 Hz), 3.73 (dd, 1H, J2.6, 11.2 Hz), 1.52 (s,
3H), 1.50 and 1.47 (each s, each 9H), 1.33 (s, 3H), 0.82
(s, 9H), 0.04 and 0.02 (each s, each 3H); 13C NMR
(CDCl3) 161.19, 152.74, 149.38, 132.19, 131.69, 122.68,
113.70, 93.23, 86.84, 86.11, 82.20, 82.01, 81.13, 63.53,
28.03, 27.27, 25.84, 25.54, 18.28, 25.51, 25.68.
Acknowledgements
We would like to thank Ms Matsumoto and Ms Maeda