P. Y. F. Deghati et al. / Bioorg. Med. Chem. 11 (2003) 899–908
907
2H), 3.78 (m, 3H), 2.29 (m, 3H), 1.75 (m, 3H); 13C
NMR (CDCl3): d 158.6, 151.1, 148.4, 145.6, 141.2,
129.7, 128.1, 127.0, 126.7, 123.4, 121.5, 97.9, 64.6, 61.8,
36.1, 32.3, 31.4, 23.6; HR-MS calcd for C17H18N5O3S
m/z=372.1131 (M+H), found 372.1104.
stirring a mixture of 51 (315 mg, 1.38 mmol), 6-mercap-
topurine (245 mg, 1.55 mmol) and K2CO3 (228 mg,
1.65 mmol) in DMF (5 mL) at rt for 3 h. (general
method A). After addition of water (30 mL) the mixture
was allowed to stand at 5 ꢀC for 4 days. An oily residue
separated from the water layer. After removal of the
water layer, toluene (20 mL) was added and evaporated
in vacuo. This procedure was repeated twice after which
the remaining residue was dissolved in DMF (10 mL).
At 0 ꢀC NaH (60% dispersion in mineral oil, 70 mg,
1.75 mmol) was added. After 30 min n-butylbromide
(200 mL, 1.85 mmol) was added. The reaction was stirred
overnight at rt and poured into water (40 mL). Extrac-
tion with EtOAc (3 ꢃ 20 mL), drying (MgSO4) and
concentration in vacuo gave an orange oil that was
purified by silicagel column chromatography (n-hep-
tane/EtOAc=2/1) to afford 55 (245 mg, 50%) as a white
4-[6-(4-Nitrobenzylsulfanyl)-9H-purine-9-yl]butan-1-ol (47).
Compound 46 was made from 42 by general method B
in 86% yield. 1H NMR (CDCl3): d 8.65 (s, 1H), 8.05 (d,
1H, J=9.2 Hz), 7.97 (s, 1H), 7.70 (d, 1H, J=9.2 Hz),
4.65 (s, 2H), 4.42 (m, 1H), 4.21 (m, 3H), 3.72 (m, 3H),
3.33 (m, 3H), 2.12 (m, 3H), 1.51 (m, 4H).
Deprotection of 46 was achieved with p-toluene sulfonic
1
acid to give 47 in 65% yield. H NMR (CDCl3): d 8.70
(s, 1H), 8.36 (s, 1H), 8.10 (d, 2H, J=9.2 Hz), 7.70 (d, 2H,
J=9.2 Hz), 4.82 (broad s, 1H), 4.74 (s, 2H), 4.43 (t, 2H,
J=7.3 Hz), 3.57 (t, 2H, J=7.3 Hz), 1.97 (m, 2H), 1.51
(m, 2H); 13C NMR (CDCl3): d 159.2, 151.7, 148.9, 147.2,
145.8, 143.0, 132.1, 131.9, 129.9, 128.6, 123.7, 62.1, 43.9,
31.8, 29.2, 27.0. Mp: 128–130 ꢀC; HR-MS calcd for
C16H19N5O3S m/z=360.1130 (M+H), found 360.1123.
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solid. H NMR (CDCl3): d 9.11 (s, 1H), 8.77 (s, 1H),
7.95 (s, 1H), 7.86 (s, 1H), 7.79 (d, 1H, J=9.5 Hz), 7.55
(d, 1H, J=9.5 Hz), 4.77 (s, 2H), 4.28 (t, 2H, J=6.6 Hz),
1.89 (m, 2H), 1.33 (m, 2H), 0.95 (t, 3H, J=7.3 Hz); 13C
NMR (CDCl3): d 160.6, 159.5, 151.4, 148.4, 143.9,
142.6, 134.2, 133.5, 130.9, 130.3, 121.4, 121.2, 43.4, 32.3,
31.6, 19.5, 13.1. Mp: 93–94 ꢀC; HR-MS calcd for
C17H17N5BrS2 m/z=434.0109 (M+H), found 434.0080.
6-(4-Nitrobenzylsulfanyl)-9-cyclopentyl-9H-purine (48).
This compound was obtained from 42 by method B in
1
56% yield. H NMR (CD3OD): d 8.73 (s, 1H), 8.16 (d,
2H, J=9.2 Hz), 8.02 (s, 1H), 7.65 (d, 2H, J=9.2 Hz),
4.96 (m, 1H), 4.72 (s, 2H), 2.29 (m, 1H), 1.97.80 (m,
8H); 13C NMR (CDCl3): d 158.6, 151.1, 148.4, 145.6,
141.2, 129.7, 126.7, 123.4, 56.1, 32.3, 31.0, 23.6. Mp: 92–
94 ꢀC; HR-MS calcd for C17H18N5O2S m/z=356.1181
(M+H), found 356.1179.
6-(3-Bromo-benzo-[2,1]-isothiazol-5-yl)methylsulfanyl-
9H-purine (52). This compound was made by general
method A, from bromide 30 in 90% yield as a white
solid. 1H NMR (DMSO-d6): d 8.79 (s, 1H), 8.48 (s, 1H),
7.79 (m, 2H), 7.67 (d, 1H, J=9.5 Hz), 4.85 (s, 2H), 3.33
(b, s, 1H, NH); 13C NMR (DMSO-d6) d 160.3, 156.9,
151.3, 150.6, 143.7, 135.9, 133.8, 132.7, 131.7, 129.2,
122.0, 119.5, 31.3.
9-But-1-yl-6-(4-nitrobenzylsulfanyl)-9H-purine (53). This
compound was prepared by general method A from 42
in 98% yield. 1H NMR (DMSO-d6): d 8.76 (s, 1H), 8.52
(s, 1H), 8.18 (d, J=8.77 Hz), 7.76 (d, J=8.77 Hz), 4.79
(s, 2H), 4.25 (t, 2H, J=7.31 Hz), 1.82 (tt, 2H,
J=7.31 Hz), 1.24 (tq, 2H, J=7.31 Hz), 0.89 (t, 3H,
J=7.31 Hz); HR-MS calcd for C16H18N5O2S m/
z=344.1181 (M+H), found 344.1148.
1-[6-(3-Bromo-benzo[c]isothiazol-5-yl)methylsulfanyl-9H-
purine-9-yl]butane (56). This compound was prepared
by the general method D from 52 and n-butylbromide in
1
69% yield. H NMR (CDCl3): d 8.78 (s, 1H), 7.95 (s,
1H), 7.71 (m, 2H), 7.57 (d, 1H, J=9.5 Hz), 4.78 (s, 2H),
4.25 (t, 2H, J=6.6 Hz), 1.89 (m, 2H), 1.34 (m, 2H), 0.96
(t, 3H, J=7.3 Hz); 13C NMR (CDCl3): d 160.7, 159.3,
151.4, 148.5, 142.6, 134.9, 134.0, 131.9, 131.1, 130.9,
122.1, 119.7, 43.5, 32.3, 31.7, 19.6, 13.2. Mp: 118–
119 ꢀC; HR-MS calcd for C17H18N5S2 m/z=356.1003
(M+H), found 356.0927.
6-(Benzo[1,2,5]oxadiazol-4-ylmethylsulfanyl)-9H-purine
(50). This compound was prepared by general method
1
A, from 49 and bromide 12 in 88% yield. H NMR
(CD3OD): d 8.77 (s, 1H), 8.13 (s, 1H), 7.72 (d, 1H,
J=8.77 Hz), 7.57 (d, 1H, J=6.58 Hz), 7.32 (dd, 1H,
J=8.77, 5.84 Hz), 5.07 (s, 2H).
5-Chloro-7-benzylsulfanyl-3-ꢀ-D-ribofuranosyl-3H-imi-
dazo[4,5-b]pyridine (60). A mixture of 57 (166 mg,
0.37 mmol), benzylthiol (65 mg, 0.60 mmol) and 0.02 mL
of Et3N in 2 mL of DMF was stirred at rt for 18 h under
N2 atmosphere. The solution was extracted with ether,
dried and purified by flash chromatography (PE/EA, 1:1),
yielding 5-chloro-7-(benzylsulfanyl)-3-(20,30,50-tri-O-acetyl
-b-d-ribofuranosyl)-3H-imidazo[4,5-b]pyridine 58 (168mg)
1-[6-(Benzo[1,2,5]oxadiazol-4-ylmethylsulfanyl-9H-
purine-9-yl]butane (54). This compound was made by
general method D from 50 and n-butyl bromide in 63%
1
yield. H NMR (CD3OD): d 8.76 (s, 1H), 7.93 (s, 1H),
7.63 (d, 1H, J=8.77 Hz), 7.52 (d, 1H, J=6.58 Hz), 7.26
(dd, 1H, J=6.58, 8.78 Hz), 4.97 (s, 2H), 4.20 (t, 2H,
J=7.31 Hz), 1.83 (t, 2H, J=7.31 Hz), 1.28 (t, 2H,
J=7.31 Hz), 0.89 (t, 3H, J=7.31 Hz); 13C NMR
(CDCl3): d 151.5, 145.6, 142.7, 129.8, 123.4, 121.3, 98.1,
43.6, 31.7, 31.4, 19.6, 13.2; HR-MS calcd for
C16H17N6OS (M+H), 341.1106 found 341.1184.
1
in 85% yield. H NMR (CDCl3): d 8.13 (s, 1H), 7.42.31
(m, 5H), 7.08 (s, 1H), 6.23 (d, 1H, J=5.1 Hz), 5.85 (dd,
1H, J=5.1, 5.9 Hz), 5.65 (dd, 1H, J=5.1, 5.9 Hz), 4.43 (s,
2H), 4.38 (m, 2H), 2.28 (s, 1H), 2.12 (s, 1H), 1.90 (s, 1H).
Deprotection of 58 with a saturated solution of ammo-
nia in methanol at 0 ꢀC for 18 h gave 83 mg of 60 (65%).
1H NMR (CD3OD): d 8.60 (s, 1H), 7.40.29 (m, 5H),
1-[6-(Benzo-[2,1]-isothiazol-5-yl)methylsulfanyl-9H-
purine-9-yl]butane (55). This compound was made by