Youcef et al.
ethyl acetate 8:2) to give 4a (0.41 g, 79%) as a yellow solid;
mp ) 122-124 °C; [R]28D ) -3.40 (c 1.0, CHCl3); IR (ATR, cm-1
4-ꢀ-D-Ribosyl-1,2,3-triazole (9). The compound 4a (0.070 g,
0.12 mmol) was dissolved in methanol (5 mL), and Pd(OH)2/C
(20%) was added. The reaction mixture was hydrogenated at room
temperature for 24 h under 5 bar. The catalyst was removed after
filtration on Celite and washed with MeOH. The solvents were then
evaporated to give 9 (0.070 g, 99%) as a white solid; mp )
)
3061, 2888, 1479, 1454, 1349, 1048, 910, 751, 671; 1H NMR (400
MHz, CDCl3) δ 3.59 (dd, J ) 10.5, 3.7 Hz, 1H), 3.75 (dd, J )
10.5, 2.8 Hz, 1H), 4.05 (dd, J ) 6.9, 5.0 Hz, 1H), 4.25 (t, J ) 4.1
Hz, 1H), 4.31 (m, 1H), 4.42 (d, J ) 11.9 Hz, 1H), 4.44 (d, J )
11.9 Hz, 1H), 4.49 (d, J ) 11.9 Hz, 1H), 4.60 (d, J ) 11.9 Hz,
1H), 4.68 (d, J ) 11.9 Hz, 1H), 4.75 (d, J ) 11.9 Hz, 1H), 5.19
(d, J ) 15.1 Hz, 1H), 5.29 (d, J ) 3.1 Hz, 1H), 5.36 (d, J ) 15.1
Hz, 1H), 7-7.3 (m, 20H), 7.31 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 54.0, 69.4, 72.0, 72.1, 73.3, 76.7, 80.6, 80.8, 122.5,
127.7-128.7, 129.0, 134.7, 137.8, 137.9, 138.2, 148.2. HRMS-
CI: m/z [M + H]+ calcd for C35H35N3O4, 561.2628; found 561.2634.
1-Benzyl-5-(2,3,5-tri-O-benzyl-ꢀ-D-ribosyl)-1,2,3-triazole (4b).
118-120 °C; [R]28 ) +11.3 (c 1.0, CH3OH); IR (ATR, cm-1
)
D
1
3335, 2965, 2374, 1675, 995, 897. H NMR (400 MHz, CD3OD)
δ 3.63 (dd, J ) 11.9, 5.0 Hz, 1H), 3.77 (dd, J ) 11.9, 3.2 Hz, 1H),
3.95 (dd, J ) 7.8, 4.6 Hz, 1H), 4.12 (dd, J ) 10.1, 5.5 Hz, 1H),
4.14 (t, J ) 5.5 Hz, 1H), 4.95 (s, 1H), 7.66 (s, 1H); 13C NMR (100
MHz, CD3OD) δ 62.2, 71.3, 76.2, 77.6, 84.8, 128.0, 143.9. HRMS-
CI: m/z [M + H]+ calcd for C7H11N3O4, 201.0750; found 201.0746.
1-Benzyl-5-(2,3-isopropylidene-ꢀ-D-ribosyl)-1,2,3-triazole-4-
carboxamide (10). A solution of compound 8b (0.100 g, 0.224
mmol) in MeOH (5 mL) was cooled to -10 °C and treated with
gaseous NH3. The solution was maintained at -10 °C for 8 h and
then warmed to room temperature overnight. The reaction mixture
was evaporated, and the residue was purified by silica gel column
chromatography (petroleum ether/ethyl acetate 1:1) to give 10
1
Obtained as a mixture with 4a. Yellow oil, H NMR (400 MHz,
CDCl3) 3.39 (dd, J ) 3.7, 10.6 Hz, 1H), 3.44 (dd, J ) 3.7, 10.6
Hz, 1H), 3.85 (dd, J ) 10.9, 5 Hz, 1H), 3.95 (dd, J ) 4.6, 6.9 Hz,
1H), 4.16 (m, 1H), 4.2 (m, 1H), 4.35 (m, 2H), 4.4 (m, 1H), 4.48
(m, 2H), 4.9 (d, J ) 7.3 Hz, 1H), 5.46 (d, J ) 15 Hz, 1H), 5.5 (d,
J ) 15 Hz, 1H), 7-7.3 (m, 20H), 7,42 (s, 1H). HRMS-CI: m/z
[M + H]+ calcd for C35H35N3O4, 561.2628; found 561.2639.
Ethyl 3-(2,3-Isopropylidene-5-acetyl-ꢀ-D-ribosyl)propiolate
(7). Indium (0,272 g, 2.19 mmol) was stirred during 30 min under
vacuum/argon in a sealed tube. Then a solution of ethyl iodopro-
piolate 6 (0.408 g, 1.82 mmol) and 1,5-diacetyl-2,3-isopropylidene
riboside 5 (0.25 g, 0.91 mmol) in anhydrous CH2Cl2 (9 mL) was
introduced in the medium, which was refluxed for 3 days. The
mixture was evaporated, and the residue was directly purified by
flash column chromatography (cyclohexane/ethyl acetate 8:2) to
give 7 (0.17 g, 60%) as a yellow oil; [R]28D ) -0.68 (c 1.0, CHCl3);
IR (ATR, cm-1) 2985, 1743,1710, 1220, 1066, 860, 749. 1H NMR
(400 MHz, CDCl3) δ 1.24 (t, J ) 6.9 Hz, 3H), 1.27 (s, 3H), 1.45
(s, 3H), 2.05 (s, 3H), 4.11 (dd, J ) 5.5, 11.9 Hz, 1H) 4.16 (q, J )
6.9 Hz, 2H), 4.19 (dd, J ) 4.6, 11.5 Hz, 1H), 4.80 (dt, J ) 2.3, 5.0
Hz, 1H), 4.67 (dd, J ) 2.3, 6.0 Hz, 1H), 4.74 (d, J ) 2.3 Hz, 1H);
4,83 (dd, J ) 2.3, 6.0 Hz, 1H); 13C NMR (400 MHz, CDCl3) δ
13.9, 20.8, 25.1, 26.8, 62.26, 63.8, 74.7, 78.4, 82.8, 83.4, 83.8, 85.8,
114.1, 152.8, 170.5. HRMS-EI: m/z [M]+ calcd for C15H20O7,
312.1209; found 312.1210.
(0.080 g, 83%) as a white powder; mp ) 178-180 °C; [R]28
)
D
-22.39 (c 1.0, CHCl3); IR (ATR, cm-1) 3409, 3278, 2921, 1730,
1
1663, 1602, 1466, 1245, 1054, 870; H NMR (400 MHz, CDCl3)
δ 1.22 (s, 3H), 1.40 (s, 3H), 3.72 (dd, J ) 12.4, 11.2 Hz, 1H), 3.86
(d, J ) 12.4 Hz, 1H), 4.18 (s, 1H), 4.24 (d, J ) 11.2 Hz, 1H), 4.97
(m, 3H), 5.60 (d, J ) 15.5 Hz, 1H), 5.62 (d, J ) 15.5 Hz, 1H),
7.12-7.29 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 20.8, 23.0,
48.3, 57.9, 71.9, 72.1, 77.0, 79.9, 81.0, 110.4, 122.4, 124.2, 124.7,
124.8, 129.6, 132.4, 134.6, 158.12. HRMS-CI: m/z [M + H]+ calcd
for C18H22N4O5, 374.1590; found 374.1585.
1-Benzyl-5-ꢀ-D-ribosyl-1,2,3-triazole-4-carboxamide (11). To
a solution of compound 10 (0.067 g, 0.179 mmol) in methanol/
water (4:1) (5 mL) was added Dowex 50WX8 (0.5 g). The reaction
mixture was stirred at 50 °C for 6 h, then filtered and washed with
MeOH. After solvent evaporation, the crude powder 11 (0.041 g,
69%) was directly used directly for the next step without any further
purification; mp ) 208-210 °C; [R]28D ) +3.95 (c 1.0, CH3OH);
IR (ATR, cm-1) 3389, 2937, 1652, 1497, 1286, 1111, 872; 1H NMR
(400 MHz, CD3OD) δ 3.60 (dd, J ) 12.4, 2.7 Hz, 1H), 3.64 (dd,
J ) 12.4, 3.2 Hz, 1H), 3.83 (d, J ) 2.7 Hz, 1H), 3.93 (dd, J ) 6.0,
3.2 Hz, 1H), 4.03 (dd, J ) 7.8, 6.4 Hz, 1H), 5.36 (d, J ) 7.8 Hz,
1H), 5.75 (d, J ) 15.6 Hz, 1H), 5.8 (d, J ) 15.6 Hz, 1H), 7.2 (m,
5H); 13C NMR (100 MHz, CD3OD) δ 61.8, 70.9, 74.7, 75.2, 86.9,
126.9, 127.8, 128.5. HRMS-CI: m/z [M + H]+ calcd for
C15H18N4O5, 334.1277; found 334.1256.
Ethyl 1-Benzyl-4-(2,3-isopropylidene-5-acetyl-ꢀ-D-ribosyl)-
1,2,3-triazole-5-carboxylate (8a). To a solution of ethyl ribosyl-
propiolate 7 (0.100 g, 0.320 mmol) in water (10 mL) were added
benzyl azide (0.043 g, 0.320 mmol) and SDS (0.02 mmol). The
mixture was stirred at 70 °C for 24 h. After evaporation of the
solvent, the crude product was purified by flash column chroma-
tography (cyclohexane/ethyl acetate 9:1) to give compounds 8a
(0.022 g, 15%) and 8b (0.061 g, 43%). Compound 8a: yellow oil;
[R]28D ) -36.78 (c 1.0, CHCl3); IR (ATR, cm-1) 2984, 1725, 1497,
1370, 1211, 1097, 859; 1H NMR (400 MHz, CDCl3) δ 1.27 (t, J )
7.2 Hz, 3H), 1.30 (s, 3H), 1.51 (s, 3H), 1.97 (s, 3H), 4.05 (d, J )
5.2 Hz, 2H), 4.21 (m, 1H), 4.29 (q, J ) 7.2 Hz, 2H), 4,77 (dd,
J ) 6.4, 3.2 Hz, 1H), 5.22 (dd, J ) 6.4, 3.2 Hz, 1H), 5.46 (d, J )
3.3 Hz, 1H), 5.78 (d, J ) 14.2 Hz, 1H), 5.82 (d, J ) 14.2 Hz, 1H),
7.23 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 13.9, 20.8, 25.4,
27.2, 53.9, 62.1, 64.2, 76.4, 78.1, 82.6, 83.4, 83.9, 114.2, 125.7,
128.0, 128.5, 128.8, 134.7, 148.4, 158.2, 170.6. HRMS-CI: m/z
[M + H]+ calcd for C22H27N3O7, 445.1849; found 455.1828.
Ethyl 1-Benzyl-5-(2,3-isopropylidene-5-acetyl-ꢀ-D-ribosyl)-
1,2,3-triazole-4-carboxylate (8b). Yellow solid; mp ) 75-77 °C;
[R]28D ) -1.63 (c 1.0, CHCl3); IR (ATR, cm-1) 2989, 1739, 1728,
5-ꢀ-D-Ribosyl-1,2,3-triazole-4-carboxamide (12). Compound
11 (0.100 g, 0.267 mmol) was dissolved in methanol (5 mL), and
Pd/C (10%) was added. The reaction mixture was hydrogenated at
room temperature for 24 h under 5 bar. The catalyst was removed
after filtration on Celite and washed with MeOH. The solvents were
then evaporated to give 12 (0.07 g, 99%) as a yellow solid; mp )
204-206 °C; [R]28 ) +13.82 (c 1.0, CH3OH); IR (ATR, cm-1
)
D
1
3327, 2927, 2365, 1670, 1540, 1459, 1225, 1110, 995, 897; H
NMR (400 MHz, CD3OD) δ 3.72 (dd, J ) 12.4, 3.7 Hz, 1H), 3.85
(dd, J ) 12.4, 2.8 Hz, 1H), 4.01 (dd, J ) 3.7, 2.8 Hz, 1H), 4.14 (s,
2H), 5.38 (d, J ) 3.7 Hz, 1H); 13C NMR (100 MHz, CD3OD) δ
61.2, 70.1, 75.8, 76.1, 84.7. HRMS-CI: m/z [M + H]+ calcd for
C8H12N4O5, 244.0808; found 244.0811.
Ethyl 1-Benzyl-4-ꢀ-D-ribosyl-1,2,3-triazole-5-carboxylate (13).
To a solution of compound 8a (0.115 g, 0.258 mmol) in methanol/
water (4:1) (10 mL) was added Dowex 50WX8 (1.30 g). The
mixture was stirred at 50 °C for 6 h, then filtered and washed with
MeOH. After solvent evaporation, the crude 13 (0.100 g, 99%)
obtained as a yellow oil was used directly for the next step without
any further purification. [R]28D ) +5.22 (c 1.0, CH3OH); IR (ATR,
cm-1) 3269, 2928, 2499, 1722, 1455, 1256, 1102, 1029, 852, 730;
H NMR (400 MHz, CD3OD) δ 1.26 (t, J ) 7.1 Hz, 3H), 3.67 (dd,
J ) 11.9, 4.1 Hz, 1H), 3.82 (dd, J ) 11.9, 2.8 Hz, 1H), 3.99 (ddd,
J ) 5.1, 4.1, 2.8 Hz, 1H), 4.24 (dd, J ) 5.5, 5.1 Hz, 1H), 4.32-4.37
1
1439, 1379, 1237, 1188, 1096, 858; H NMR (400 MHz, CDCl3)
δ 1.13 (s, 3H), 1.35 (t, J ) 7.2 Hz, 3H), 1.46 (s, 3H), 1.99 (s, 3H),
4,05 (d, J ) 5.0 Hz, 1H), 4.24 (m, 2H), 4.35 (m, 2H), 4.37 (m,
1H), 4.43 (dd, J ) 6.9, 5.0 Hz, 1H), 5.50 (d, J ) 5.0 Hz, 1H), 5.63
(d, J ) 16 Hz, 1H), 5.71 (d, J ) 16 Hz, 1H), 7.27 (m, 5H); 13C
NMR (100 MHz, CDCl3) δ 10.0, 16.5, 20.9, 22.9, 26.6, 48.8, 57.2,
59.2, 76.7, 81.3, 82.7, 84.3, 111.8, 127.0, 128.0, 128.7, 129.1, 130.5,
133.3, 133.4, 156.7, 166.2. HRMS-CI: m/z [M + H]+ calcd for
C22H27N3O7, 445.1849; found 455.1864.
4322 J. Org. Chem. Vol. 74, No. 11, 2009