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Synthesis, X-ray crystal structure and computational study of novel
pyrazolo[3,4-b]pyridin-3-ol derivatives.
Li-Qun Shen1,2, Yong Tang, Ai-Qun Wu, Dan Pan, Kai-Sheng Diao*
1
College of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Guangxi
Key Laboratory of Chemistry and Engineering of Forest Products, Nanning 530006, China
2
Hechi University, Yizhou 546300, China
E-mail: liqunshen@126.com
Supplemental Materials
Synthesis of 2,6-Dichloro-4-methylnicotinamide 115
A solution of 2,6-dichloro-4-methylnicotinonitrile (5.0 g, 26.7 mmol) in concentrated H2SO4
(25 mL) was heated at 80 °C for 4 h, then the resulting solution was cooled to 25 °C, and poured
into ice water (100 mL). The suspension was filtered and the filter cake was washed thoroughly
with water. The filter cake recrystallized from acetone to give the product (4.05 g, 80.9 %) as a
white solid .
mp: 173.5-175 °C (lit 169-173 °C). 1H NMR ((CD3)2SO): δ 8.10 (s, 1H), 7.93 (s, 1H), 7.55 (s,
1H), 2.31 (s, 3H). IR (KBr): 3444, 3343, 3169, 1682, 1577, 1081, 917, 848 cm-1.
6-Hydrazino-4-methyl-1-H-pyrazolo[3,4-b]pyridine-3-ol 216
A solution of 2,6-dichloro-4-methylnicotinamide (1, 5.000 g, 4.9 mmol) in 80 % hydrazine
hydrate (5 mL) was heated at 100 °C for 5 h, then the resulting solution was cooled to room
temperature, and a yellow solid formed. The yellow solid product was isolated filtration and the
filter was washed with 95 % ethanol to give 2 (3.44 g, 71.8 %). mp > 300 °C. 1H NMR (600
MHz, (CD3)2SO): δ 11.56 (s, 1H), 10.35 (s, 1H), 7.97 (s, 1H), 6.09 (s, 1H), 4.2 (brs, 2H), 2.37 (s,
3H). IR (KBr): 3395, 3325, 3207, 1619, 1505, 1306, 1015,747 cm-1. The product was used
without further purification.
6-(3,5-Dimethyl-pyrazol-1-yl)-4-methyl-1H-pyrazolo[3,4-b]pyridin-3-ol 3a16
To a solution of 6-hydrazino-4-methyl-1-H-pyrazolo[3,4-b]pyridine-3-ol (0.9 g, 5.0 mmol) in
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ethanol (10 mL) was added 2,4-pentanedione (1 mL, 9.7 mmol). The reaction mixture was stirred
at room temperature for 30 min, then was heated to 80 °C for 3h. The yellow solution was
evaporated in vacuum, the residue was isolated by filtration and the filter was washed with cold
methanol. The filter cake recrystallized from ethanol to obtain 3a as an white solid ( 1.0 g,
75.8 %). mp: 270.1-271.9 °C . 1H NMR (600 MHz, (CD3)2SO): δ 11.89 (s, 1H), 10.94 (s, 1H),
7.32 (s, 1H), 6.11 (s, 1H), 2.61 (s, 3H), 2.49 (s, 3H), 2.19 (s, 3H).
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C NMR (150 MHz,
(CD3)2SO): δ 13.5, 14.5, 17.8, 102.3, 107.9, 109.3, 141.2, 146.2, 149.0, 151.8, 153.0, 157.1.
IR(KBr) 3638, 3141, 3089, 2929, 1602, 1567, 1553, 1390, 1289, 903, 827 cm-1. HRMS(m/z):
Calcd. for C12H13N5O: 243.1120 Found: 243.1117.
Figure S 1: View along a axis showing the H-bonds in compound 3a
Table S 1: Hydrogen bond geometry of 3a, 4-6 (Å and °)
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DH···A
3a
N2H2···N5c
O1H1···N1b
4
N4H4···O1c
N7H7···O1d
O1H1D···N1
0
O1H1E···N1
5
N2H2···O1e
O1H1A···N1
DH (Å)
H···A ( Å)
D···A(Å)
0.86
0.82
2.17
1.89
3.002(3)
2.712(3)
162.8
173.7
0.86
0.86
0.85
2.06
2.05
1.99
2.87
2.85
2.84
156.0
155.8
172.6
0.85
1.99
2.84
174.6
0.86
0.85
1.90
2.08
2.75
2.92
169.7
170.1
O1H1B···N5
0.85
2.13
2.97
170.2
6
N2H2···O4
O4H4A···N5
0.86
0.85
2.08
2.01
2.87
2.86
152.0
177.1
O4H4B···N5
0.85
2.01
2.86
177.1
DH···A (° )
Symmetry codes:a -x+1/2,
y+1/2, -z+1/2; b-x, -y, z+1; c x+1, y, z; d x+1, y,
z; e x, y, z−1; f−x+1, −y+1,
−z+1; g x+1, y, z+1; h x,
y−1, z; l−x+1/2, y−1,
−z+1/2
f
g
h
l
Figure S 2: Packing diagram of molecular structure of compounds 4∙ H2O
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Figure S 3: Packing diagram of molecular structure of compounds 5∙H2O
Figure S 4: Packing diagram of molecular structure of compounds 6∙H2O
HOMO
LUMO
Figure S 5: B3LYP/6-31+G* HOMO (top) and LUMO (bottom) orbitals of the compound 3a at
the 0.02 a.u. level