334 JOURNAL OF CHEMICAL RESEARCH 2007
Methyl 5-deoxy-5-(pyrimidin-2-ylamino)-β-d-ribofuranosides 4a–d
Compounds 3a–d (0.25 g) were refluxed in 80% aqueous acetic acd
(10 ml) for 2 h. The solvents were removed in vacuo and the residue
coevaporated with water (4 ¥ 5 ml) and finally EtOH (3 × 5 ml).
The residue was purified on column chromatography using 10%
MeOH in CHCl3 to give 4a–d in 67–71% yields.
J = 6.5 Hz, H-5), 4.39 (t, 1 H, J = 6.5 Hz, H-4), 4.50 (d, 1 H, J = 5.9 Hz,
H-3), 4.59 (d, 1 H, J = 5.9 Hz, H-2), 5.07 (s, 1 H, H-1). EI-MS:
m/z (%): 247 (67). Anal. Calcd. for C11H21NO5: C, 53.43; H, 8.56;
N, 5.66. Found: C, 53.23; H, 8.29; N, 5.39%.
Methyl 2,3-O-isopropylidene-5-(pyrimidin-2-ylaminoethyl)-β-d-ribo-
furanosides 9a–d
Methyl 5-deoxy-5-(pyrimidin-2-ylamino)-b-d-ribofuranoside (4a):
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Yield 70% as a white foam. H NMR (DMSO-d6) d: 3.35 (s, 3 H,
Asolution of 2a–d (5 mmol) and 8 (1.23 g, 5 mmol) in ethanol (20 ml)
was stirred under reflux for 3–5 h (TLC). The solvent was removed
in vacuo and the residue was chromatographed on a silica gel column
using 5% MeOH in CHCl3 to give 9a–d in 80–88% yields.
Methyl 2,3-O-isopropylidene-5-(pyrimidin-2-ylaminoethyl)-β-d-
OMe), 4.41–4.55 (m, 3 H, H-4', H-5'), 4.70–4.81 (m, 2 H, H-2', H-
3'), 5.01 (s, 1 H, H-1'), 5.25 (d, 1 H, J = 5.9 Hz, 3'-OH), 5.56 (d, 1 H,
J = 5.9 Hz, 2'-OH), 6.50 (d, 1 H, J = 5.0 Hz, H-5), 7.00 (t, 1 H, J = 4.1
Hz, NH), 8.20 (d, 1 H, J = 5.0 Hz, H-6). EI-MS: m/z (%): 257 (51).
Anal. Calcd. for C10H15N3O5: C, 46.69; H, 5.87; N, 16.33. Found: C,
46.53; H, 5.66; N, 16.16%.
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ribofuranoside (9a): Yield 85% as a white foam. H NMR (CDCl3)
d: 1.33 (s, 3H, CH3), 1.44 (s, 3H, CH3), 3.34 (s, 3H, OMe), 4.38–4.82
(m, 9H, H-2', H-3', H-4', H-5', OCH2, NCH2), 5.08 (s, 1H, H-1'), 6.78
(d, 1H, J = 5.0 Hz, H-5), 7.08 (t, 1H, J = 4.1 Hz, NH), 7.17 (d, 1H,
J = 5.0 Hz, H-6), 10.01 (brs, 1H, NH). EI-MS: m/z (%): 341 (15).
Anal. Calcd. for C15H23N3O6: C, 52.78; H, 6.79; N, 12.31. Found: C,
52.70; H, 6.66; N, 12.23%.
Methyl 2,3-O-isopropylidene-5-(5-methylpyrimidin-2-ylaminoethyl)-
β-d-ribofuranoside (9b): Yield 88% as a white foam. 1H NMR
(CDCl3) d: 1.31 (s, 3H, CH3), 1.47 (s, 3H, CH3), 2.08 (s, 3H, CH3),
3.38 (s, 3H, OMe), 4.35–4.80 (m, 9H, H-2', H-3', H-4', H-5', OCH2,
NCH2), 5.02 (s, 1H, H-1'), 7.00 (t, 1H, J = 4.0 Hz, NH), 8.09 (s, 1H,
H-6), 10.01 (brs, 1H, NH). EI-MS: m/z (%): 355 (17). Anal. Calcd.
for C16H25N3O6: C, 54.07; H, 7.09; N, 11.82. Found: C, 54.00; H,
6.97; N, 11.62%.
Methyl 2,3-O-isopropylidene-5-(6-methylpyrimidin-2-ylaminoethyl)-
β-d-ribofuranoside (9c): Yield 83% as a white foam. 1H NMR
(CDCl3) d: 1.33 (s, 3H, CH3), 1.48 (s, 3H, CH3), 2.39 (s, 3H, CH3),
3.35 (s, 3H, OMe), 4.30–4.79 (m, 9H, H-2', H-3', H-4', H-5', OCH2,
NCH2), 5.00 (s, 1H, H-1'), 6.32 (s, 1H, H-5), 6.99 (t, 1H, J = 4.2 Hz,
NH), 9.95 (brs, 1H, NH). EI-MS: m/z (%): 355 (14). Anal. Calcd. for
C16H25N3O6: C, 54.07; H, 7.09; N, 11.82. Found: C, 53.93; H, 7.01;
N, 11.77%.
Methyl 2,3-O-isopropylidene-5-(6-propylpyrimidin-2-ylaminoethyl)-
β-d-ribofuranoside (9d): Yield 80% as a white foam. 1H NMR
(CDCl3) d: 0.99 (t, 3H, J = 7.5 Hz, CH3), 1.42 (s, 3H, CH3), 1.60
(s, 3H, CH3), 1.80–1.99 (m, 2H, CH2), 2.57–2.69 (m, 2H, CH2),
3.35 (s, 3H, OMe), 4.33–4.84 (m, 9H, H-2', H-3', H-4', H-5', OCH2,
NCH2), 5.01 (s, 1H, H-1'), 6.29 (s, 1H, H-5), 6.96 (t, 1H, J = 4.0 Hz,
NH), 9.99 (brs, 1H, NH). EI-MS: m/z (%): 383 (13). Anal. Calcd. for
C18H29N3O6: C, 56.38; H, 7.62; N, 10.96. Found: C, 56.31; H, 7.53;
N, 10.82%.
Methyl 5-deoxy-5-(5-methylpyrimidin-2-ylamino)-b-d-ribofurano-
side (4b): Yield 71%. M.p. 116–117°C. 1H NMR (DMSO-d6) d: 2.10
(s, 3 H, CH3), 3.35 (s, 3 H, OMe), 4.48–4.58 (m, 3 H, H-4', H-5'),
4.78 (d, 1 H, J = 5.9 Hz, H-3'), 4.88 (d, 1 H, J = 5.9 Hz, H-2'), 5.01
(s, 1 H, H-1'), 5.31 (d, 1 H, J = 5.9 Hz, 3'-OH), 5.61 (d, 1 H, J = 5.9
Hz, 2'-OH), 7.05 (t, 1 H, J = 4.2 Hz, NH), 8.02 (s, 1 H, H-6). EI-MS:
m/z (%): 271 (67). Anal. Calcd. for C11H17N3O5 C, 48.70; H, 6.31; N,
15.48. Found: C, 48.60; H, 6.21; N, 15.37%.
Methyl 5-deoxy-5-(6-methylpyrimidin-2-ylamino)-b-d-ribofurano-
side (4c): Yield 69%. M.p. 134–135°C. 1H NMR (DMSO-d6) d: 2.35
(s, 3 H, CH3), 3.35 (s, 3 H, OMe), 4.45–4.55 (m, 3 H, H-4', H-5'),
4.61 (d, 1 H, J = 5.8 Hz, H-3'), 4.75 (d, 1 H, J = 5.8 Hz, H-2'), 5.02 (s,
1 H, H-1'), 5.30 (d, 1 H, J = 5.9 Hz, 3'-OH), 5.60 (d, 1 H, J = 5.9 Hz,
2'-OH), 6.28 (s, 1 H, H-5), 7.02 (t, 1 H, J = 4.0 Hz, NH). EI-MS: m/z
(%): 271 (54). Anal. Calcd. for C11H17N3O5: C, 48.70; H, 6.31; N,
15.48. Found: C, 48.63; H, 6.36; N, 15.50%.
Methyl 5-deoxy-5-(6-propylpyrimidin-2-ylamino)-b-d-ribofurano-
side (4d): Yield 67%. M.p. 154–156°C. 1H NMR (DMSO-d6) d: 0.95
(t, 3 H, J = 7.2 Hz, CH3), 1.60–1.75 (m, 2 H, CH2), 2.50–2.65 (m,
2 H, CH2), 3.35 (s, 3 H, OMe), 4.45–4.55 (m, 3 H, H-4', H-5'), 4.62
(d, 1 H, J = 5.9 Hz, H-3'), 4.73 (d, 1 H, J = 5.9 Hz, H-2'), 5.01 (s,
1 H, H-1'), 5.30 (d, 1 H, J = 5.9 Hz, 3'-OH), 5.60 (d, 1 H, J = 5.9 Hz,
2'-OH), 6.28 (s, 1 H, H-5), 7.01 (t, 1 H, J = 4.0 Hz, NH). EI-MS: m/z
(%): 299 (44). Anal. Calcd. for C13H21N3O5: C, 52.16; H, 7.07; N,
14.03. Found: C, 52.23; H, 7.17; N, 14.20%.
Methyl 2,3-O-isopropylidene-5-O-[2-(p-toluenesulfonyloxyethyl)]-
b-d-ribofuranoside (6): p-Toluenesulfonyl chloride (9.52 g, 50 mmol)
was added in a small portions to a stirred cold solution of 5 (12.15 g,
49 mmol) in dry pyridine (100 ml). The reaction mixture was
stirred overnight at room temperature. The solvent was evaporated
and coevaporated with toluene. The residue was dissolved in water
(100 ml) and extracted with dichloromethane (3×50 ml). The organic
layer was dried over Na2SO4 and evaporated under reduced pressure
to give 6 (17.72 g, 90%). M.p. 91–93°C. 1H NMR (CDCl3) d: 1.28 (s,
3 H, CH3), 1.44 (s, 3 H, CH3), 2.42 (s, 3 H, CH3), 3.29 (s, 3 H, OMe),
3.67 (d, 2 H, J = 6.5 Hz, H-5), 3.88–4.00 (m, 4 H, 2xOCH2), 4.31 (t,
1 H, J = 6.5 Hz, H-4), 4.52 (d, 1 H, J = 5.9 Hz, H-3), 4.61 (d, 1 H, J =
5.9 Hz, H-2), 4.99 (s, 1 H, H-1), 7.35 (d, 2 H, J = 7.9 Hz, Ar-H), 7.70
(d, 2 H, J = 8.0 Hz, Ar-H). EI-MS: m/z (%): 402 (19). Anal. Calcd.
for C18H26O8S: C, 53.72; H, 6.51. Found: C, 53.60; H, 6.31%.
Methyl 2,3-O-isopropylidene-5-O-phthalimidoethyl-β-d-ribofurano-
side (7):Asuspension of 6 (11.25 g, 28 mmol), potassium phthalimide
(6.7 g, 36 mmol) and sodium iodide (8 g) in dry DMF (100 ml) was
heated at about 150°C for 20 min. The resulting solution was cooled
and poured into 1l of ice water. The colourless crystals which formed
were collected by filtration and washed with water to yield 9.81 g
Methyl 5-(pyrimidin-2-ylaminoethyl)-β-d-ribofuranosides 10a–d
Compounds 9a–d (0.25 g) were refluxed in 70% aqueous acetic acd
(10 ml) for 2 h. The solvents were removed in vacuo and the residue
was coevaporated with water (4×5 ml) and finally EtOH (3×5 ml).
The residue was purified on column chromatography using 10%
MeOH in CHCl3 to afford 10a–d in 70–80% yields.
Methyl 5-(pyrimidin-2-ylaminoethyl)-β-d-ribofuranoside (10a):
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Yield 78%. M.p. 133–135°C. H NMR (DMSO-d6) d: 3.36 (s, 3H,
OMe), 4.43–4.90 (m, 9H, H-2', H-3', H-4', H-5', OCH2, NCH2), 5.01
(s, 1H, H-1'), 5.29 (d, 1H, J = 5.9 Hz, 3'-OH), 5.59 (d, 1H, J = 5.9 Hz,
2'-OH), 6.48 (d, 1H, J = 5.0 Hz, H-5), 7.03 (t, 1H, J = 4.1 Hz, NH),
8.18 (d, 1H, J = 5.0 Hz, H-6), 9.98 (brs, 1H, NH). EI-MS: m/z (%):
301 (34). Anal. Calcd. for C12H19N3O6: C, 47.84; H, 6.36; N, 13.95.
Found: C, 47.77; H, 6.23; N, 13.79%.
Methyl 5-(5-methylpyrimidin-2-ylaminoethyl)-β-d-ribofuranoside
(10b): Yield 80%. M.p. 139–141°C. 1H NMR (DMSO-d6) d: 2.13 (s,
3H, CH3), 3.39 (s, 3H, OMe), 4.45–4.98 (m, 9H, H-2', H-3', H-4',
H-5', OCH2, NCH2), 5.04 (s, 1H, H-1'), 5.37 (d, 1H, J = 5.9 Hz, 3'-
OH), 5.67 (d, 1H, J = 5.9 Hz, 2'-OH), 7.04 (t, 1H, J = 4.2 Hz, NH),
8.00 (s, 1H, H-6), 9.97 (brs, 1H, NH). EI-MS: m/z (%): 315 (29).
Anal. Calcd. for C13H21N3O6: C, 49.52; H, 6.71; N, 13.33. Found: C,
49.43; H, 6.54; N, 13.19%.
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(93%). M.p. 145–147°C. H NMR (CDCl3) d: 1.30 (s, 3 H, CH3),
1.43 (s, 3 H, CH3), 3.32 (s, 3 H, OMe), 3.60 (d, 2 H, J = 6.5 Hz, H-5),
3.68 (m, 2 H, OCH2), 4.08 (m, 2 H, NCH2), 4.37 (t, 1 H, J = 6.5 Hz,
H-4), 4.49 (d, 1 H, J = 5.9 Hz, H-3), 4.58 (d, 1 H, J = 5.9 Hz, H-2),
5.09 (s, 1 H, H-1), 7.95 (m, 2 H, Ar–H), 8.09 (m, 2 H, Ar–H). EI-MS:
m/z (%): 377 (15). Anal. Calcd. for C19H23NO7: C, 60.47; H, 6.14; N,
3.71. Found: C, 60.34; H, 6.05; N, 3.49%.
Methyl 5-O-(2-aminoethyl)-2,3-O-isopropylidene-b-d-ribofurano-
side (8): A solution of 7 (2.82 g, 7.5 mmol) and 80% hydrazine
hydrate (2 ml) in methanol (20 ml) was heated under reflux for 2 h.
The methanol was removed in vacuo from the resulting suspension,
and the white solid residue was dissolved in 40 ml of water and
acdified to pH 1. The precpitate of phthalhydrazine was removed by
filtration, and the colourless filtrate was brought to pH > 12. The basic
solution was extracted three times with 30 ml of dichloromethane
and the extracts were dried. Evaporation of the solvent gave 1.64 g
Methyl 5-(6-methylpyrimidin-2-ylaminoethyl)-β-d-ribofuranoside
(10c): Yield 75%. M.p. 176–177°C. 1H NMR (DMSO-d6) d: 2.33 (s,
3H, CH3), 3.38 (s, 3H, OMe), 4.45–4.98 (m, 9H, H-2', H-3', H-4',
H-5', OCH2, NCH2), 5.02 (s, 1H, H-1'), 5.33 (d, 1H, J = 5.9 Hz, 3'-
OH), 5.67 (d, 1H, J = 5.9 Hz, 2'-OH), 6.33 (s, 1H, H-5), 7.05 (t, 1H,
J = 4.0 Hz, NH), 9.96 (brs, 1H, NH). EI-MS: m/z (%): 315 (26). Anal.
Calcd. for C13H21N3O6: C, 49.52; H, 6.71; N, 13.33. Found: C, 49.47;
H, 6.66; N, 13.21%.
Methyl 5-(6-propylpyrimidin-2-ylaminoethyl)-β-d-ribofuranoside
(10d): Yield 70%. M.p. 199–201°C. 1H NMR (DMSO-d6) d: 0.94 (t,
3H, J = 7.2 Hz, CH3), 1.63–1.79 (m, 2H, CH2), 2.50–2.69 (m, 2H,
CH2), 3.38 (s, 3H, OMe), 4.45–4.98 (m, 9H, H-2', H-3', H-4', H-5',
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(89%) of the colourless liquid amine. H NMR (CDCl3) d: 1.33 (s,
3 H, CH3), 1.44 (s, 3 H, CH3), 2.12 (brs, 2 H, NH2), 2.59 (m, 2 H,
NCH2), 3.34 (s, 3 H, OMe), 3.48 (m, 2 H, OCH2), 3.58 (d, 2 H,
PAPER: 07/4562