1016
Chem. Pharm. Bull.
Vol. 64, No. 7 (2016)
yl-3H-pyrazol-3-one (10b)
A
solution of 14 (2.70g, (s), 157.67 (s), 169.34 (s), 169.45 (s), 170.27 (s), 170.77 (s).
7.70mmol) in THF (30mL) was hydrogenated over 10% Pd/C HR-MS (ESI) m/z: 591.2554 [M+H]+ (Calcd for C29H39N2O11:
(50% wet, 0.30g) for 10h at room temperature under atmo- 591.2548).
spheric pressure. The Pd–C was filtered off and the filtrate was
4-[(4-Isopropoxyphenyl)methyl]-5-methyl-3-(2,3,4,6-
concentrated under reduced pressure to provide 10b (1.98g, tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole
(2a)
99%) as a white solid. mp 160–162°C. IR (KBr) cm−1: 1613, A mixture of 11a (0.618g, 1.0mmol) and KHCO3 (0.030g,
1
1540, 1511, 1372, 1300. H-NMR (DMSO-d6) δ: 1.22 (6H, d, 0.30mmol) in MeOH (3mL) was stirred at 50°C for 1h;
J=6.0Hz), 2.03 (3H, s), 3.45 (2H, s), 3.47 (3H, s), 4.46–4.55 AcOH (0.018g, 0.30mmol) was then added at room tempera-
(1H, m), 6.76 (2H, d, J=8.5Hz), 7.03 (2H, d, J=8.5Hz), 9.37 ture. After the reaction mixture was concentrated under re-
(1H, brs). 13C-NMR (DMSO-d6) δ: 9.31(q), 21.76 (q×2), 26.56 duced pressure, the residue was purified by silica gel chroma-
(t), 34.97 (q), 68.87 (d), 100.95 (s), 115.27 (d×2), 128.76 (d×2), tography (eluent AcOEt–n-hexane, 1:2) to provide 2a (0.259g,
133.59 (s), 136.22 (s), 155.24 (s), 157.91 (s). HR-MS (ESI) m/z: 45% yield). An analytical sample of 2a was obtained as a
261.1609 [M+H]+ (Calcd for C15H21N2O2: 261.1598).
white solid by recrystallization from Et2O. mp 155–156°C.
1-Acetyl-4-[(4-isopropoxyphenyl)methyl]-5-methyl- [α]D20 −7.9 (c=1.0, DMSO). IR (KBr) cm−1: 3393, 3222, 2978,
3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H- 2943, 1751, 1735, 1612, 1509, 1474, 1434, 1374. 1H-NMR
pyrazole (11a) 5a (0.987g, 2.4mmol) was added to a mix- (CDCl3) δ: 1.30 (6H, dd, J=2.3, 5.9Hz), 1.89 (3H, s), 2.01 (3H,
ture of 10a (0.577g, 2.0mmol) and K2CO3 (0.387g, 2.8mmol) s), 2.03 (3H, s), 2.05 (3H, s), 2.10 (3H, s), 3.55 (2H, dd, J=15.7,
in MeCN (5mL), and the reaction mixture was stirred for 11.7Hz), 3.83–3.87 (1H, m), 4.11 (1H, dd, J=2.3, 12.5Hz), 4.31
16h at 60°C. The mixture was diluted with AcOEt (20mL) (1H, dd, J=4.1, 12.3Hz), 4.43–4.52 (1H, m), 5.18–5.30 (3H,
and washed with H2O (5mL). The resulting organic layer was m), 5.58 (1H, d, J=6.8Hz), 6.75 (2H, d, J=8.8Hz), 7.02 (2H,
concentrated under reduced pressure. The residue was purified d, J=8.8Hz), 9.09 (1H, brs). 13C-NMR (CDCl3) δ: 10.36 (q),
by silica gel chromatography (eluent AcOEt–n-hexane, 1:3) to 20.48 (q), 20.61 (q), 20.63 (q), 20.72 (q), 22.07 (q), 22.10 (q),
provide 11a (1.11g, 90% yield). An analytical sample of 11a 26.50 (t), 61.64 (t), 68.07 (d), 69.89 (d), 70.93 (d), 72.06 (d),
was obtained as a white solid by recrystallization from Et2O. 72.92 (d), 97.67 (d), 103.54 (s), 115.84 (d×2), 129.12 (d×2),
mp 68–72°C. [α]D20 −19.3 (c=1.0, dimethyl sulfoxide (DMSO)). 132.69 (s), 138.21 (s), 156.05 (s), 159.89 (s), 169.31 (s), 169.44
IR (KBr) cm−1: 3436, 2977, 2934, 1759, 1611, 1509, 1472, 1431, (s), 170.30 (s), 170.76 (s). HR-MS (ESI) m/z: 577.2380 [M+H]+
1
1373, 1336. H-NMR (CDCl3) δ: 1.29 (3H, dd, J=3.8, 6.2Hz), (Calcd for C28H37N2O11: 577.2392).
1.86 (3H, s), 2.02 (3H, s), 2.04 (3H, s), 2.06 (3H, s), 2.50 (3H,
1-Acetyl-4-[(4-isopropoxyphenyl)methyl]-5-methyl-3-
s), 2.55 (3H, s), 3.54 (2H, dd, J=15.6, 19.9Hz), 3.86–3.91 (2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-
(1H, m), 4.16 (1H, dd, J=2.3, 12.5Hz), 4.27 (1H, dd, J=4.8, pyrazole (11c) 5b (1.39g, 2.4mmol) was added to a mixture
12.2Hz), 4.43–4.52 (1H, m), 5.18 (1H, t, J=9.6Hz), 5.24–5.33 of 10a (0.577g, 2.0mmol) and K2CO3 (0.387g, 2.8mmol) in
(2H, m), 5.71 (1H, d, J=7.8Hz), 6.75 (2H, d, J=8.5Hz), 7.01 MeCN (5mL), and the mixture was stirred for 16h at 60°C.
(2H, d, J=8.5Hz). 13C-NMR (CDCl3) δ: 13.12 (q), 20.41 (q), The reaction mixture was diluted with AcOEt (20mL) and
20.60 (q×2), 20.71 (q), 22.03 (q), 22.09 (q), 23.19 (q), 26.25 washed with H2O (5mL). The resulting organic layer was con-
(t), 61.82 (t), 68.17 (d), 69.87 (d), 70.62 (d), 72.48 (d), 72.83 (d), centrated under reduced pressure. The obtained residue was
96.67 (d), 111.39 (s), 115.93 (d×2), 129.13 (d×2), 131.30 (s), purified by silica gel chromatography (eluent AcOEt–n-hexane,
141.76 (s), 156.31 (s), 160.45 (s), 169.15 (s), 169.42 (s), 170.23 1:3) to provide 11c (1.44g, 92% yield). An analytical sample
(s), 170.61 (s), 170.85 (s). HR-MS (ESI) m/z: 619.2473 [M+H]+ of 10c was obtained as a white solid by recrystallization from
(Calcd for C30H39N2O12: 619.2498).
n-hexane. mp 137–140°C. [α]D20 −2.0 (c=1.0, DMSO). IR (KBr)
4-[(4-Isopropoxyphenyl)methyl]-1,5-dimethyl-3-(2,3,4,6- cm−1: 3469, 2975, 2936, 2875, 1747, 1612, 1509, 1480, 1470,
1
tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole (11b) 1398, 1370, 1333. H-NMR (CDCl3) δ: 1.01 (9H, s), 1.13 (9H,
5a (0.987g, 2.4mmol) was added to a mixture of 10b (0.521 g, s), 1.16 (9H, s), 1.18 (9H, s), 1.29 (6H, dd, J=2.4, 6.1Hz), 2.47
2.0mmol) and K2CO3 (0.387g, 2.8mmol) in MeCN (5mL) (3H, s), 2.54 (3H, s), 3.53 (2H, s), 3.88–3.92 (1H, m), 4.12–4.20
and the reaction mixture was stirred for 16h at 60°C. The (2H, m), 4.42–4.51 (1H, m), 5.23 (1H, t, J=9.7Hz), 5.28–5.33
reaction mixture was diluted with AcOEt (20mL) and washed (1H, m), 5.43 (1H, t, J=9.4Hz), 5.84 (1H, d, J=8.2Hz),
with H2O (5mL). The resulting organic layer was concentrated 6.74–6.78 (2H, m), 7.01–7.04 (2H, m). 13C-NMR (CDCl3) δ:
under reduced pressure. The residue was purified by silica 13.19 (q), 22.05 (q), 22.10 (q), 23.22 (q), 26.23 (t), 26.88 (q×3),
gel chromatography (eluent AcOEt–n-hexane, 1:1) to provide 27.03 (q×6), 27.15 (q×3), 38.66 (s), 38.74 (s), 38.77 (s), 38.83
11b (0.311g, 26%). An analytical sample of 11b was obtained (s), 61.61 (t), 67.64 (d), 69.83 (d), 70.71 (d), 72.21 (d), 72.89 (d),
as a white solid by recrystallization from Et2O-n-hexane. mp 97.00 (d), 111.52 (s), 115.96 (d×2), 129.17 (d×2), 131.23 (s),
65–69°C. [α]D20 −11.2 (c=1.0, DMSO). IR (KBr) cm−1: 2977, 141.82 (s), 156.30 (s), 160.57 (s), 170.88 (s), 176.38 (s), 176.40
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1759, 1751, 1508, 1496, 1371. H-NMR (CDCl3) δ: 1.29 (6H, (s), 177.20 (s), 178.03 (s). HR-MS (ESI) m/z: 787.4373 [M+H]+
dd, J=1.9, 6.3Hz), 1.90 (3H, s), 2.01 (3H, s), 2.03 (3H, s), 2.06 (Calcd for C42H63N2O12: 787.4376).
(3H, s), 2.07 (3H, s), 3.54 (2H, dd, J=16.0, 14.7Hz), 3.60 (3H,
4-[(4-Isopropoxyphenyl)methyl]-5-methyl-3-(2,3,4,6-
s), 3.82–3.86 (1H, m), 4.09–4.16 (1H, m), 4.30 (1H, dd, J=4.3, tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole (2b)
12.5Hz), 4.42–4.51 (1H, m), 5.17–5.29 (3H, m), 5.53–5.55 (1H, A mixture of 11c (0.787g, 1.0mmol) and KHCO3 (0.030g,
m), 6.74 (2H, d, J=8.7Hz), 7.02 (2H, d, J=8.7Hz). 13C-NMR 0.30mmol) in MeOH (3mL) was stirred at 50°C for 1h;
(CDCl3) δ: 9.92 (q), 20.53 (q), 20.62 (q), 20.65 (q), 20.75 (q), AcOH (0.018g, 0.30mmol) was then added at room tem-
22.07 (q), 22.10 (q), 26.88 (t), 35.77 (q), 61.71 (t), 68.18 (d), perature. After the reaction mixture had been concentrated
69.85 (d), 70.98 (d), 71.94 (d), 72.96 (d), 97.76 (d), 103.62 under reduced pressure, the residue was purified by silica gel
(s), 115.78 (d×2), 129.06 (d×2), 133.09 (s), 137.63 (s), 155.97 chromatography (eluent AcOEt–n-hexane, 1:2) to provide