Synthesis and transformations of substituted 4,6-dimethylpyrazolo[3,4-b] pyridyl-3-azides and -sulfonyl chlorides

Article abstract of DOI:10.1007/s10593-009-0169-y

Diazotization of the amino group of 3-amino-4,6-dimethylpyrazolo[3,4-b] pyrimidines and subsequent replacement of the diazo group in the formed diazonium chlorides by an azide group gave the corresponding 3-azido derivatives. Their reactions with active methylene compounds have been studied. Substitution of the diazo group by a sulfo group gave the related 4,6-dimethylpyrazolo-[3,4-b]pyridyl-3-sulfonyl chlorides and sulfonylamides.

Full text of DOI:10.1007/s10593-009-0169-y

Chemistry of Heterocyclic Compounds, Vol. 44, No. 10, 2008
SYNTHESIS AND TRANSFORMATIONS
OF SUBSTITUTED 4,6-DIMETHYLPYRA-
ZOLO[3,4-b]PYRIDYL-3-AZIDES AND
-SULFONYL CHLORIDES
I. G. Dmitrieva1, L. V. Dyadyuchenko2, V. D. Strelkov2, and E. A. Kaigorodova1
Diazotization of the amino group of 3-amino-4,6-dimethylpyrazolo[3,4-b]pyrimidines and subsequent
replacement of the diazo group in the formed diazonium chlorides by an azide group gave the
corresponding 3-azido derivatives. Their reactions with active methylene compounds have been
studied. Substitution of the diazo group by a sulfo group gave the related 4,6-dimethylpyrazolo-
[3,4-b]pyridyl-3-sulfonyl chlorides and sulfonylamides.
Keywords: azides, pyrazolo[3,4-b]pyrimidines, sulfonylamides, sulfonyl chlorides, diazotization,
substitution, mass spectra, synthesis, elimination.
We have previously reported [1] the synthesis of the 3-aminopyrazolo[3,4-b]pyridines 1a-d which can
be used as starting materials in the synthesis of novel chemical materials with differently useful properties. With
this in view we report in the current study an investigation of the possible diazotization of the amino group in
compounds 1a-d and subsequent substitution of the diazo group in the diazonium chlorides formed by an azide
group to give azido derivatives and by a sulfo group to give the corresponding sulfonyl chlorides (Scheme 1).
The 3-aminopyrazolo[3,4-b]pyridines 1a-d show aromatic amine properties and readily undergo
diazotization in hydrochloric acid solution from -2 to 0°C to give the corresponding diazonium chlorides 2a-d.
Compounds 2a-c react with a saturated sodium azide solution from -1 to +1°C (optimum conditions) to form the
3-azido-4,6-dimethylpyrazolo[3,4-b]pyridines 3a-c in high yields (76-84%). When carrying out the reaction of
salts 2a-c with hydrazine under an analogous temperature regime according to a known method [2] the yield of
the azide derivatives 3a-c is significantly lower (54-67%).
It was found that the reaction of the diazonium chloride 2d both with sodium azide and with hydrazine did
not give the corresponding azido derivative but in both cases gave the 3,5-dichloro-4,6-dimethyl-
(1H)pyrazolo[3,4-b]pyridine 4. The reaction conditions could not be varied to yield the target 3-azido-5-chloro-
4,6-dimethyl-(1H)pyrazolo[3,4-b]pyridine. In all likelihood the diazonium chloride 2d is characterized by greater
instability, the rate of elimination of the diazo group being greater than its substitution by the azide group.
Azides 3a-c are colorless, crystalline materials stable to light but changing in color to a bright-yellow upon
storage in light.
__________________________________________________________________________________________
1Kuban State Agrarian University, Krasnodar 350044, Russia; e-mail: chem._dmitrieva@mail.ru, e-mail:
e_kaigorodova@mail.ru. 2All-Russian Research Institute of Biological Plant Protection, Krasnodar 350039, Russia;
e-mail: vladstrelkov@yandex.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1556-1565,
October, 2008. Original article submitted November 22, 2006; revision submitted June 10, 2008.
0009-3122/08/4410-1267©2008 Springer Science+Business Media, Inc.
1267

1
The physicochemical and spectroscopic characteristics, elemental analytical data, and the H NMR
spectra of azides 3a-c are given in Table 1 and the mass spectra in Table 2.
The IR spectra of compounds 3a-c show a characteristic azide group absorption in the range
1
2121-2138 cm-1 [3]. The H NMR spectra show signals for all of the protons of compounds 3a-c in the
corresponding regions.
Scheme 1
R3
N
R2
O
Me
N
S
NH2
N
Me
R
O
R
N
N
R1
Me
N
Me
N
R1
8a–h
1а–d
R3R2NH
HNO2
Cl
O
+
O
–
Me
N2 Cl
Me
N
Me
Cl
S
R
Cl
R
SO2
– N2
N
N
N
R1
N
N
R1
N
Me
N
Me
Me
N
H
4
7a–c
2a–d
N
N
O
NaN3
N3
N
N
C
N
Me
Me
N
Me
N
N
Me
R
R
R
Me
NH2
N
N
R1
N
N
R1
N
N
R1
Me
N
Me
Me
N
6a–c
3a–c
5a–c
2–7 a R = R1 = H, b R = H, R1 = Me, c R = Cl, R1 = Me, d R = Cl, R1 = H; 8 a–f R = H, a R1 = H,
R2, R3 = (CH2CH2)2CH–Me; b R1 = Н, R2 = Me, R3 = CH2CH2OH; c R1 = R2 = H,
R3 = 2-ClC6H4CH2; d R1= Me, R2 = H, R3 = furfuryl; е R1 = Me; R2 = R3 = CH2CH=CH2;
f R1= R2= Me; R3 =PhCH2; g R = Cl; R1 = Me; R2 = H, R3 = 4-MeOC6H4;
h R = Cl; R1 = Me, R2, R3 = (CH2CH2)2CH–Me
The mass spectra of azides 3a-c show molecular ion peaks with relatively low intensities (3-19%). At
the primary stage of fragmentation all three compounds 3a-c show the elimination of two molecules of N2 from
the molecular ion to give the quite stable fragments F1 which then undergo loss of an R1 fragment and HCN
molecule (Scheme 2).
Scheme 2
.
.
.
+
+
+
N3
N
N
N
N
R
R
R
R
– 2 N2
F3
N
N
– R1
– HCN
N
+
N
N
N
N
R1
N
N
R1
+
R1
F1
F2
M
1268

It is known that organic azides form 1,2,3-triazoles with 1,3-diketones and β-keto esters [4-6]. We have
studied the reactions of the previously unreported azides 3a-c with acetylacetone and malononitrile.
Heating the azides 3a-c with excess acetylacetone in the presence of Et3N base gave the 4,6-dimethyl-
3-(1,2,3-triazolyl)pyrazolo[3,4-b]pyridines 5a-c (Scheme 1). The reaction occurs upon refluxing in acetonitrile over
4-6 h. Reaction of azides 3a-c under milder conditions occurs at 55-60ºC in a proton solvent medium in the
presence of Et3N base to give the 3-(5-amino-4-cyano-1,2,3-triazolyl)-4,6-dimethylpyrazolo[3,4-b]pyridines 6a-c.
The cycloaddition of acetylacetone and malononitrile to the azido group occurs selectively to form
single reaction products in agreement with literature data [4, 5]. The yield of addition products 5a-c, 6a-c was
56-81%. The structure was confirmed by mass and 1H NMR spectroscopic data (Tables 1-3).
When compared with the starting azides 3a-c the 1H NMR spectra of compounds 5a-c show signals for
the protons of two methyl groups as singlets with δ 2.11-2.14 ppm (5-CH3 triazole) and 2.69-2.72 ppm
(COCH3). The spectra of derivatives 6a-c show NH2 protons signals as a broadened singlet at 7.41-7.46 ppm.
The mass spectra of derivatives 5a-c, 6a-c show molecular ion peaks with relative intensities 6-72%.
Under electron impact conditions the triazole ring first undergoes destruction as reflected in the general
fragmentation for compounds 5a-c (Scheme 3). In addition, all of the compounds are also characterized by
clevage of the C–N bond joining the pyrazole and triazole rings in the molecular ion with possible transfer of a
hydrogen atom from the ortho-positioned methyl group to the pyrazole C(3).
Scheme 3
.
+
N
N
N
+
– N2
N
– COMe
Het
N
N
Het
N
O
Het
N
+
+
F5
F7
M
– N2
– HCN
.
+
N
O
N
Het
N
N
O
Het
N
+
F4
N
N
F6
N
O
.
+
Het –H
F8
+
Het
F9
In order to synthesize the 4,6-dimethylpyrazolo[3,4-b]pyridyl-3-sulfonyl chlorides 7a-d (Scheme 1) the
diazonium chlorides 2a-d were added dropwise to a saturated solution of SO2 in glacial acetic acid. Anhydrous
copper sulphate was used as the catalyst. The use of optimized conditions (0-4ºC) allowed the preparation of the
sulfonyl chlorides 7a-c in 68-93% yield. It was found that the diazonium chloride 2d and SO2 gave a mixture
very difficult to resolve containing mainly the 3-chloro derivative 4 and a small amount of the target sulfonyl
1
chloride (10-15% according to H NMR spectroscopy), while a change in reaction conditions did not lead to a
marked increase in the yield of the latter.
The synthesized sulfonyl chlorides 7a-c are light-yellow crystalline materials hydrolyzing readily upon
storage in air (Table 1).
As might be expected, the 1H NMR spectra of the sulfonyl chlorides 7a-c showed signals for the protons
of the pyrazolopyridine system shifted to lower field when compared with the corresponding azides 3a-c and
this is explained by the effect of the strongly electron attracting SO2Cl group (Table 2).
1269

The mass spectrometric behavior of the products 7a-c is similar. The spectra of all of the compounds
(Table 3) show the presence of highly stable molecular ion peaks (54-100%). The initial fragmentation occurs in
two directions, i.e. elimination of a chlorine molecular ion and the loss of the SO2 molecule. The later stages of
the fragmentation show the destruction of the pyrazole ring through the elimination of a N2 molecule.
By reaction of the sulfonyl chlorides 7a-c with different amines we have prepared a series of
N-alkyl(aryl, heteryl)-substituted pyrazolo[3,4-b]pyridyl-3-sulfonylamides 8a-h (Scheme 1). The synthesis was
carried out in anhydrous benzene medium in the presence of Et3N as hydrogen chloride acceptor. The high
reactivity of the sulfonyl chlorides even allowed the preparation of the substituted sulfonylamides 8a-h at room
temperature in quite high yields (64-88%) (Table 1).
TABLE 1. Physicochemical Characteristics of Compounds 3-8
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °C
Yield, %
С
Н
N
3a
3b
3c
4
C8H8N6
50.68
51.06
52.88
52.46
45.41
45.68
44.16
44.47
56.81
56.24
58.60
59.14
52.58
52.75
51.39
51.96
53.49
53.72
47.15
47.61
39.40
39.11
41.89
41.62
36.46
36.75
54.83
54.52
46.15
46.47
51.58
51.35
4.43
4.28
5.25
4.98
4.20
3.83
3.40
3.27
5.16
4.72
6.02
5.67
5.16
4.74
4.30
3.96
4.80
4.51
3.92
3.66
3.14
3.28
3.71
3.88
3.18
3.08
6.31
6.54
5.83
5.67
4.16
4.31
44.12
44.66
41.31
41.56
35.19
35.51
19.64
19.44
31.12
31.09
29.41
29.56
25.99
26.36
43.82
44.07
41.34
41.77
36.60
37.01
17.29
17.10
15.97
16.18
14.03
14.28
18.22
18.17
19.65
19.70
15.82
15.97
206-207 (EtOH)
95-96 (hexane)
76
84
78
52
56
81
69
66
80
74
76
68
93
81
71
74
64
72
76
65
69
C9H10N6
C9H9ClN6
115-116 (cyclohexane)
188-190 (EtOH)
Dec. ≈280 (DMF)
156-158 (EtOAc)
197-199 (EtOH)
Dec. ≈330 (DMF)
Dec ≈290 (DMF)
Dec 262-265 (DMF)
238-240 (MeCN)
108-109 (hexane)
115-116 (hexane)
204-205 (EtOH)
168-170 (EtOAc)
198-200 (EtOH)
96-97 (hexane)
C8H7Cl2N3
5a
5b
5c
6a
6b
6c
7a
7b
7c
8a
8b
8c
8d
8e
8f
C13H14N6O
C14H16N6O
C14H15ClN6O
C11H10N8
C12H12N8
C12H11ClN8
C8H8ClN3O2S
C9H10ClN3O2S
C9H9Cl2N3O2S
C14H20N4O2S
C11H16N4O3S
C15H15ClN4O2S
C14H16N4O3S
C15H20N4O2S
C17H20N4O2S
C16H17ClN4O3S
C15H21ClN4O2S
52.23
52.49
56.41
56.23
58.99
59.28
50.24
50.46
4.88
5.03
6.13
6.29
5.74
5.85
4.58
4.50
17.60
17.49
17.22
17.49
16.34
16.27
14.49
14.71
67-68 (hexane)
92-93 (hexane)
8g
8h
163-165 (EtOAc)
151-152 (EtOAc)
50.69
50.48
6.08
5.93
15.54
15.70
1270

1
The H NMR spectra of the sulfonylamides 8a-h showed both the signals for the pyrazolopyridine
system protons and all of the protons signals corresponding to the amine component of the molecule (Table 2).
The IR spectra of sulfonylamides 8a-h showed the presence of two strong, characteristic bands in the
regions 1315-1332 and 1149-1166 cm-1 which respectively correspond to the asymmetric and symmetric
stretching absorption bands of the SO2 group [3]. In addition the spectra contain medium intensity N–H
absorption bands in the region 3174-3286 cm-1 (Experimental section).
By contrast to the sulfonyl chlorides 7a-c under electron impact conditions the sulfonylamides Het–
SO2NR2R3 8a-h form very unstable molecule ions and in the majority of cases they are absent in the mass
spectra. The typical direction of breakdown of the molecule ion is dissociation of the Het–S bond but the
maximum intensity occurs for the fragment peaks [NR2N3]+. Due to the low information available from the mass
spectra of amides 8a-h they are not reported in this publication.
TABLE 2. 1H NMR Spectra of Compounds 3-8
Com-
pound
Chemical shifts*, δ, ppm (J, Hz)
3a
3b
3c
4
13.16 (1Н, br. s, N–Н); 6.82 (1Н, s, Н-5); 2.61 (3H, s, 6-CH3); 2.55 (3H, s, 4-CH3)
6.82 (1Н, s, Н-5); 3.93 (3Н, s, N–СН3); 2.56 (3H, s, 6-CH3); 2.45 (3H, s, 4-CH3)
3.94 (3Н, s, N–СН3); 2.71 (3H, s, 6-CH3); 2.62 (3H, s, 4-CH3)
13.82 (1Н, br. s, N–Н); 2.74 (3H, s, 6-CH3); 2.64 (3H, s, 4-CH3)
5a
13.82 (1Н, br. s, NН); 7.09 (1Н, s, Н-5); 2.72 (3Н, s, СОCH3);
2.60 (3H, s, 6-CH3); 2.55 (3H, s, 4-CH3); 2.11 (3H, s, 5-CH3 triazole)
7.11 (1Н, s, Н-5); 4.12 (3Н, s, N–СН3); 2.72 (3Н, s, СОCH3);
2.63 (3H, s, 6-CH3); 2.55 (3H, s, 4-CH3); 2.22 (3H, s, 5-CH3 triazole)
5b
5c
4.13 (3Н, s, N–СН3); 2.69 (3Н, s, СОCH3); 2.62 (3H, s, 6-CH3);
2.55 (3H, s, 4-CH3); 2.14 (3H, s, 5-CH3 triazole)
6a
6b
14.08 (1Н, br. s, N–Н); 7.46 (2Н, br. s, NН2); 7.05 (1Н, s, Н-5);
2.66 (3H, s, 6-CH3); 2.18 (3H, s, 4-CH3)
7.41 (2Н, br. s, NН2); 7.10 (1Н, s, Н-5); 4.09 (3Н, s, N–СН3);
2.62 (3H, s, 6-CH3); 2.17 (3H, s, 4-CH3)
7.45 (2Н, br. s, NН2); 4.11 (3Н, s, N–СН3); 2.73 (3H, s, 6-CH3); 2.22 (3H, s, 4-CH3)
15.05 (1Н, br. s, N–Н); 7.20 (1Н, s, Н-5); 2.96 (3H, s, 6-CH3); 2.90 (3H, s, 4-CH3)
6c
7a
7b
7c
8a
7.12 (1Н, s, Н-5); 4.48 (3Н, s, N–СН3); 2.62 (3H, s, 6-CH3); 2.51 (3H, s, 4-CH3)
4.48 (3Н, s, N–СН3); 2.92 (3H, s, 6-CH3); 2.80 (3H, s, 4-CH3)
14.21 (1Н, br. s, N–Н); 7.08 (1Н, s, Н-5); 2.70 (3H, s, 6-CH3);
2.55 (3H, s, 4-CH3 Py); piperidine ring: 3.78 (m); 3.16 (m), 1.74 (m), 1.53 (m),
1.18 (m), 0.94 (3Н, m, 4-CH3)
8b
14.19 (1Н, br. s, N–Н); 7.08 (1Н, s, Н-5); 4.82 (1H, br. s, ОН);
3.88 (2H, t, J = 5.8, CH2OH); 3.62 (2H, t, J = 5.8, NCH2);
3.08 (3Н, s, N–СН3); 2.68 (3H, s, 6-CH3); 2.56 (3H, s, 4-CH3)
8c
14.18 (1Н, br. s, N–Н); 8.78 (1Н, br. s, SO2NH); 7.30-7.55 (4Н, m, Ar);
7.07 (1Н, s, Н-5); 4.43 (2H, s, CH2); 2.72 (3H, s, 6-CH3); 2.56 (3H, s, 4-CH3)
8d
8.54 (1Н, br. s, NH); 7.11 (1Н, s, Н-5 Py); furan ring: 7.52 (1Н, d, J5,4 = 1.8, Н-5);
6.32 (1Н, dd, J3,4 = 3.5, J5,4 = 1.8, Н-4); 6.23 (1H, d, J3,4 = 3.5, Н-3); 4.27 (2H, s, CH2);
4.04 (3H, s, N–CH3); 2.71 (3H, s, 6-CH3); 2.57 (3H, s, 4-CH3)
8e
7.09 (1Н, s, Н-5); 5.82-5.94 (2H, m, СH2CH=CH2);
5.18-5.30 (4H, m, CH2CH=CH2); 4.08 (3H, s, N–CH3);
3.96 (4H, d, J = 6.2, CH2CH=CH2); 2.81 (3H, s, 6-CH3); 2.68 (3H, s, 4-CH3)
8f
7.32-7.45 (5Н, m, C6H5); 7.05 (1Н, s, Н-5 Py); 4.52 (2H, s, CH2); 4.11 (3Н, s, N–СН3);
2.94 (3H, s, CH3–N–CH2–Ar); 2.82 (3H, s, 6-CH3); 2.71 (3H, s, 4-CH3)
8g
8h
10.50 (1Н, br. s, N–Н); 7.03 (2H, d, J = 8.9, Н-2,4 Ar); 6.83 (2H, d, J = 8.9, Н-3,5 Ar);
4.04 (3Н, s, N–СН3); 3.68 (3H, s, OCH3); 2.79 (3H, s, 6-CH3); 2.71 (3H, s, 4-CH3)
4.09 (3H, s, N–CH3); 2.82 (3H, s, 6-CH3); 2.70 (3H, s, 4-CH3); piperidine ring:
3.77 (m), 3.04 (m), 1.73 (m), 1.55 (m), 1.21 (m), 0.95 (3Н, m, 4-CH3)
_______
1
* H NMR spectra were recorded in DMSO-d6 (compounds 3-6, 8) or
CDCl3 (compound 7).
1271

TABLE 3. Electron Impact Mass Spectra of Compounds 3a-c, 4, 5a-c, 6a-c
Com-
pound*
Mass-spectrum, m/z (Irel, %)
3а
3b
3c
4
188 [М]+ (19), 132 [F1]+ (100), 131 [F2]+ (12), 117 [F1–CH3]+ (15), 104 [F3]+ (22)
202 [М]+ (6), 146 [F1]+ (31), 131 [F2]+ (29), 104 [F3]+ (32)
236 [М]+ (3), 180 [F1]+ (21), 165 [F2]+ (21), 145 [F1–Cl] (25), 103 [F2–Cl, –HCN]+ (11)
215 [М]+ (100), 180 [M–Cl]+ (58), 152 [180–N2]+ (20), 117 [152–Cl]+ (16),
90 [117–HCN]+ (16)
5a
270 [М]+ (23), 242 [F4]+ (49), 227 [F5]+ (61), 200 [F6]+ (88), 199 [F7]+ (100),
147 [F8]+ (37), 146 [F9]+ (10)
5b
5c
284 [М]+ (24), 256 [F4]+ (25), 241 [F5]+ (26), 214 [F6]+ (97), 213 [F7]+ (84),
161 [F8]+ (21), 160 [F9]+ (32)
318 [М]+ (6), 290 [F4]+ (29), 275 [F5]+ (19), 248 [F6]+ (37), 247 [F7]+ (26), 195 [F8]+ (23),
194 [F9]+ (10)
6a*
254 [М]+ (72), 226 [M–N2]+ (53), 225 [M–H, –N2]+ (13), 211 [226–CH3]+ (23),
200 [226–CN]+ (14), 199 [226–HCN]+ (50), 198 [225–HCN]+ (31),
184 [200–NH2]+ (28), 147 [M–Het]+ (26)
6b*
6c*
7a
268 [М]+ (28), 240 [M–N2]+ (77), 239 [M–Н, –N2]+ (100), 225 [M–CH3N2]+ (12),
199 [225–CN]+ (28), 160 [M–Het]+ (21), 133 [160–HCN]+ (33)
302 [М]+ (36), 274 [M–N2]+ (31), 273 [M–Н, –N2]+ (100), 233 [M–CN, –CH3N2]+ (34),
198 [233–Cl]+ (22), 195 [M–Het]+ (24), 167 [198–N2]+ (22)
245 [М]+ (59), 210 [М–Cl]+ (23), 181 [M–SO2]+ (25), 146 [210–SO2]+ (48),
118 [146–N2]+ (82), 105 [146–CN2H]+ (31), 78 [105–HCN]+ (100)
7b
259 [М]+ (85), 224 [М–Cl]+ (59), 176 [224–SO]+ (48), 160 [224–SO2]+ (100),
132 [160–N2]+ (54), 117 [160–N2, –CH3]+ (8)
7c
293 [М]+ (54), 258 [М–Cl]+ (28), 229 [M–SO2]+ (33), 210 [258–SO]+ (28),
194 [258–SO2]+ (100), 166 [194–N2]+ (37), 131 [166–Cl]+ (28)
_______
N
N
*
N
Het =
CN
HN
Hence we have found optimum conditions for the synthesis of the 3-azido-4,6-dimethylpyrazolo-
[3,4-b]pyridines 3a-c and 4,6-dimethylpyrazolo[3,4-b]pyridine-3-sulfonyl chlorides 7a-d and prepared
derivatives based on them. Amongst the sulfonylamides 8a-h synthesized there were discovered compound
having antidotal and growth regulating activity.
EXPERIMENTAL
1
IR spectra were recorded for KBr tablets on an Infra LUM FT-02 instrument. H NMR spectra were
obtained on a Bruker WM-500 radio spectrometer (500 MHz) using TMS as internal standard. Electron impact
mass spectra were recorded on a Finnigan MAT INCOS 50 instrument (ionization energy 70 eV). CHN elemental
analysis was performed on a Carol-Erba model 1106 analyzer. Monitoring of the reaction course and the purity of
the products obtained was carried out by TLC on Silufol UV-254 plates using the system hexane–acetone (1:1) and
revealed using iodine vapor.
The solvents used in the synthesis were purified from admixtures and dehydrated using known methods [7].
The starting 3-amino-4,6-dimethylpyrazolo[3,4-b]pyridines 1a-d were prepared by method [1].
4,6-Dimethyl(1H)pyrazolo[3,4-b]pyridyl-3-azide (3a). A solution of sodium nitrite (0.73 g, 9.3 mmol)
in water (2 ml) was added dropwise with stirring to a solution of 3-amino-4,6-dimethyl(1H)pyrazolo-
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[3,4-b]pyridine (1a), (1.0 g, 6.2 mmol) in conc. HCl (8 ml) at -5ºC, the reaction mixture temperature being held
in the range -1 to +1ºC. At the end of the addition the product was stirred at 0°C for a further 20-30 min and the
4,6-dimethyl(1H)pyrazolo[3,4-b]pyridine-3-yl diazonium salt 2a formed was added in small portions with
vigorous stirring of the reaction mixture to an aqueous solution of sodium azide (2.0 g, 31 mmol) cooled to -5ºC
(the temperature must not exceed 4ºC). To complete the reaction the temperature was slowly raised to room
temperature and the precipitate formed was filtered off, washed with water, and dried. Recrystallization from
ethanol gave the target product 3a (0.88 g, 76%) as colorless crystals. IR spectrum, ν, cm-1: 2952, 2927 (C–H
Me), 2131 (N3), 1614, 1606 (C=C, C=N).
Compounds 3b,c were prepared similarly. Compound 3b. IR spectrum, ν, cm-1: 2952, 2925 (C–H,
Me), 2854 (N–Me), 2138 (N3), 1598, 1581 (C=C, C=N). Compound 3c. IR spectrum, ν, cm-1: 2958, 2923 (C–
H, Me), 2851 (N–Me), 2121 (N3), 1594, 1571 (C=C, C=N).
2,5-Dichloro-4,6-dimethyl-(1H)pyrazolo[3,4-b]pyridine (4). The 2,5-dichloro-3-amino-4,6-dimethyl-
(1H)pyrazolo[3,4-b]pyridine (1b) (1.0 g, 5.1 mmol) was diazotized similarly to the above and the solution of the
diazonium chloride 2b obtained was treated with an aqueous solution of sodium azide. The precipitate was
filtered off, washed with water, and dried. Recrystallization from benzene gave product 4 (0.57 g, 52%) as
pale-yellow crystals.
3-(4-Acetyl-5-methyl-1,2,3-triazol-1-yl)-1,4,6-trimethylpyrazolo[3,4-b]pyrimidine (5b). A solution
of acetylacetone (0.93 g, 9.3 mmol) and triethylamine (0.93 g, 9.3 mmol) in acetonitrile (3 ml) was added to a
suspension of the 1,4,6-trimethylpyrazolo[3,4-b]pyridyl-3-azide 3b in acetonitrile (9 ml) and refluxed for
5.5-6 h. The reaction product was evaporated to dryness, washed with water, and dried. Recrystallization from a
mixture of hexane and ethyl acetate (1:3) gave the target product 5b (0.85 g, 81%) as colorless crystals.
Compounds 5a,c were prepared similarly.
3-(5-Amino-4-cyano-1,2,3-triazol-1-yl)-5-chloro-1,4,6-trimethylpyrazolo[3,4-b]pyridine (6c). 5-Chloro-
1,4,6-trimethyl-pyrazolo[3,4-b]pyridyl-3-azide (3c) (1.0 g, 4.2 mmol), malononitrile (0.55 g, 8.4 mmol), and
triethylamine (0.85 g, 8.4 mmol) were mixed in ethanol (10 ml) and heated at 55-60ºC for 3.5-4 h. The reaction
product was doubly diluted with water and the precipitate formed was filtered off, washed with water, and dried.
Recrystallization from acetone gave the target product 6c (0.95 g, 74%) as an amorphous, pink powder.
Compounds 6a,b were prepared similarly.
4,6-Dimethyl(1H)pyrazolo[3,4-b]pyridyl-3-sulfonyl Chloride (7a). The 3-amino-4,6-dimethyl-
(1H)pyrazolo[3,4-b]pyridine 1a (5.0 g, 31 mmol) was diazotized as described above. Anhydrous copper sulphate
(0.85 g) was added to a previously prepared saturated solution of SO2 in glacial acetic acid (30 ml) and then,
with vigorous stirring, a solution of 4,6-dimethyl(1H)pyrazolo[3,4-b]pyridyl-3-diazonium chloride was added
dropwise such that the temperature remained at 0-4ºC. At the end of the nitrogen evolution the flask contents
were poured into a 5% NaCl solution (100 ml), cooled to 0ºC, and the precipitate formed was filtered off,
washed with iced water, dried in air, and then in a vacuum desiccator (5-10 mm Hg). Recrystallization from
anhydrous acetonitrile gave the product 7a (5.8 g, 76%) as light-yellow crystals.
Compounds 7b-c were prepared similarly.
N-(2-Chlorobenzyl)-4,6-dimethyl(1H)pyrazolo[3,4-b]pyridyl-3-sulfonylamide (8c). A solution of
2-chlorobenzylamine (0.62 g, 4.4 mmol) and triethylamine (0.4 g, 4.0 mmol) in benzene (10 ml) was added at
room temperature with stirring to a suspension of compound 7a (1.0 g, 4.0 mmol) in anhydrous benzene (20 ml).
At the end of the addition stirring was continued for a further 3 h and the precipitate was filtered off, liberally
washed with warm water, and dried. Recrystallization from ethanol gave the product 8c (1.05 g, 74%) as light-
yellow crystals. IR spectrum, ν, cm-1: 3286 (N–H), 1618, 1583 (C=C, C=N arom.), 1332, 1449 (SO2).
Compounds 8a,b,d-h were prepared similarly.
Compound 8j. IR spectrum, ν, cm-1: 3174 (N–H), 1581, 1564 (C=C, C=N arom.), 1326, 1155 (SO2).
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