Use of the graebe-ullmann reaction in the synthesis of 8-methyl-γ- carboline and isomeric aromatic aza-γ-carbolines

Article abstract of DOI:10.1007/s10593-012-1127-7

Two variants of the Graebe-Ullmann reaction were used to obtain 8-methyl-5H-pyrido[4,3-b]indole (8-methyl-γ-carboline) and the conditions for this reaction were optimized. The feasibility of using this method was studied for the synthesis of a series of isomeric aromatic aza-γ- carbolines from the corresponding 1-(pyridyl)-1H-1,2,3-triazolo[4,5-c]pyridines under thermal and microwave irradiation conditions.

Full text of DOI:10.1007/s10593-012-1127-7

Chemistry of Heterocyclic Compounds, Vol. 48, No. 8, November, 2012 (Russian Original Vol. 48, No. 8, August, 2012)
USE OF THE GRAEBE-ULLMANN REACTION IN THE
SYNTHESIS OF 8-METHYL-γ-CARBOLINE AND ISOMERIC
AROMATIC AZA-γ-CARBOLINES
R. S. Alekseev1, A. V. Kurkin1, and M. A. Yurovskaya1*
Two variants of the Graebe-Ullmann reaction were used to obtain 8-methyl-5H-pyrido[4,3-b]indole
(8-methyl-γ-carboline) and the conditions for this reaction were optimized. The feasibility of using this
method was studied for the synthesis of a series of isomeric aromatic aza-γ-carbolines from the
corresponding 1-(pyridyl)-1H-1,2,3-triazolo[4,5-c]pyridines under thermal and microwave irradiation
conditions.
Keywords: 6-, 7-, 8- and 9-aza-γ-carboline, 1,6-, 2,6-, 3,6- and 4,5-diazacarbazole, 8-methyl-γ-carboline,
8-methyl-5H-pyrido[4,3-b]indole, 5H-pyrido[3',4':4,5]pyrrolo[2,3-c]pyridine, 5H-pyrido[3',4':4,5]pyrro-
lo[3,2-c]pyridine, 5H-pyrido[3',4':4,5]pyrrolo[3,2-b]pyridine, 9H-pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine,
1H-1,2,3-triazolo[4,5-c]pyridine, 3H-1,2,3-triazolo[4,5-b]pyridine, Graebe-Ullmann reaction, microwave
irradiation, paraffin, PPA.
The Graebe-Ullmann reaction, first proposed in 1896 for the synthesis of carbazoles, involves thermal
decomposition of the corresponding 1-arylbenzotriazoles [1]. This reaction was subsequently used for the
preparation of aromatic γ-carbolines by the decomposition of either 1-(4-pyridyl)-1H-1,2,3-benzotriazole [2] or
1-phenyl-1H-1,2,3-triazolo[4,5-c]pyridine as an alternative method [3] and has been commonly employed in the
synthesis of aromatic γ-carbolines. This synthesis was rather thoroughly considered in our recent review [4].
In the present work, we used the Graebe-Ullmann reaction for the synthesis of 8-methyl-γ-carboline (1),
which had not been prepared by this reaction previously. This γ-carboline derivative was selected since it can
serve as the starting compound for the preparation of aromatic analogs of well-known drugs, such as dicarbine
and latrepirdine [5].
8-Methyl-γ-carboline (1) was first prepared in 1964 by heating 2-benzyl-8-methyl-2,3,4,5-tetrahydro-
1H-pyrido[4,3-b]indole in the presence of metallic palladium. The pyridoindole precursor was synthesized from
N-benzylpiperid-4-one and p-tolylhydrazine by the Fischer reaction [6].
Either 5-methyl-1-(4-pyridin-4-yl)-1H-1,2,3-benzotriazole (2) or isomeric 1-(4-methylphenyl)-1H-1,2,3-tri-
azolo[4,5-c]pyridine (3) can be used as the starting compound for synthesis of carboline 1 by the Graebe-
Ullmann reaction. We obtained the benzotriazole 2 through an original synthetic scheme involving the
diazotation of diamine 4 obtained by the reduction of nitro derivative 5.
_______
*To whom correspondence should be addressed, e-mail: yumar@org.chem.msu.ru.
1M. V. Lomonosov Moscow State University, 1, Build. 3 Leninskie Gory, Moscow 119991, Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1326-1343, August, 2012.
Original article submitted February 28, 2012.
0009-3122/12/4808-1235©2012 Springer Science+Business Media New York
1235

Mononitrotoluidine 5 was synthesized through nitration of toluidine 6 with dilute nitric acid. Depending
on the reaction conditions, the dinitro derivative 7 was formed as a side product. In a study designed to increase
the yield of mononitrotoluidine 5 and to minimize the content of dinitrotoluidine 7, we nitrated
N-pyridyltoluidine 6 under various conditions (Table 1).
Me
+
NH3 Cl
1) SOCl2, 3 days
2) EtOH, 0°C
185–190°C, 90 min
79%
+
NH
N+
Cl
Cl
68%
N
Me
NO2
Na2S2O4
H
N
14.3% HNO3
85–90°C, 1 h
EtOH–H2O
NH
N
, 3.5 h
N
84%
Me
89%
6
5
Me
NH2
NH
Me
N
N
NaNO2, 6 N HCl
0–5°C
N
91%
N
2
N
4
Table 1 shows that the optimal conditions for preparation of mononitrotoluidine 5 feature nitration with
14.3% nitric acid at 85-90°C for 1 h. We should note that Nantka-Namirski [7] reported the mononitration of
2-(4-methylphenyl)aminopyridine in 81% yield using 27% nitric acid with the addition of a small amount of
sodium nitrite at 65-70°C for 15 min, but an attempt to extend this procedure for the preparation of the isomeric
aminopyridine 5 proved unsuccessful, and ~90% of the starting compound 6 was isolated.
Me
NO2
HNO3
N
6
5
+
N
H
NO2
7
TABLE 1. Ratio of Nitration Products from the Toluidine 6 Under Different
Reaction Conditions
HNO3 concentration, %
Ratio of nitration
reaction products*
Time, min
Temperature, °С
(ρ, g/cm3)
42.0 (1.25)
30.0 (1.18)
30.0 (1.18)
30.0 (1.18)
25.5 (1.15)
17.6 (1.10)
14.3 (1.08)
60
60
65–70
85–90
65–70
65–70
85–90
85–90
85–90
7 (100%)
5 (5%) : 7 (95%)
5 (50%) : 7 (50%)
5 (80%) : 7 (20%)
5 (40%) : 7 (60%)
5 (90%) : 7 (10%)
5 (100%)
60
150
60
60
60
_______
*From 1H NMR spectral data.
1236

In order to prepare 1,2,3-triazolo[4,5-c]pyridine 3, we carried out the following sequence of
transformations involving 4-chloro-3-nitropyridine (8) as the hetarylating agent:
98% HNO3
25% oleum
, 2 h
OH
OH
Cl
1 equiv. 4-MeC6H4NH2
PCl5, POCl3
, 6 h
NO2
NO2
i-Pr2EtN, MeCN, , 5 h
82%
95%
92%
N
N
N
8
NH2
NO2
Na2S2O4, H2O–EtOH
, 3.5 h
H
H
N
N
92%
N
N
Me
Me
10
9
N
N
NaNO2, 6 N HCl
0–5°C
N
Me
97%
N
3
This scheme involves the preparation of 4-amino-3-nitropyridine 9, the reduction of this intermediate
with sodium hydrosulfite to the corresponding 3,4-diamino derivative 10, and subsequent diazotation
accompanied by the formation of triazolo[4,5-c]pyridine 3.
A method has been described for the synthesis of nitropyridine 9 in 80% yield, consisting of the
reaction of 4-chloro-3-nitropyridine (8) with three equivalents of p-toluidine at 170°C [8]. An inconvenience of
this method lies in the significant excess of the aniline derivative, and the need for chromatographic isolation
and purification of the desired product. We have been able to retain the high yield (82%) with significant
simplification of the procedure for the isolation and purification of the nitropyridine 9 by carrying out the
reaction of chloropyridine 8 with one equivalent of p-toluidine in acetonitrile in the presence of Hunig's base
(diisopropylethylamine).
The decomposition of benzotriazole 2 and triazolopyridine 3 to prepare 8-methyl-5H-pyrido-
[4,3-b]indole (1) and the optimization of Graebe-Ullmann reaction was carried out under thermal conditions in
protic medium, such as polyphosphoric acid (PPA), and also in aprotic medium such as paraffin, or by
microwave irradiation in PPA, which has been successfully used in the synthesis of carbazoles and γ-carbolines
by the Graebe-Ullmann reaction [9]. Various conditions for carrying out this reaction and the yields of
8-methyl-γ-carboline (1) are given in Table 2.
N
, PPA or
, PPA or
Me
paraffin
paraffin
2
3
or MW, PPA
or MW, PPA
N
1
H
TABLE 2. Conditions for the Preparation and Yields of 8-Methyl-
γ-carboline (1) by the Graebe-Ullmann Reaction
Starting
compound
Method
Conditions
Yield, %
A
B
C
D
E
F
PPA, 220°С, 5–10 min
58
2
2
2
3
3
3
Paraffin, 350°С, 10 min, Ar atm.
PPA, MW 170 W, 5 min
PPA 250°С, 5–10 min
44 (1); 28* (6)
67
66
Paraffin, 370°С, 10 min, Ar atm.
PPA, MW 170 W, 5 min
48 (1); 32* (6)
72
_______
*The yields calculated from 1H NMR spectral data are given.
1237

The data in Table 2 show that carrying out the reaction in PPA gives higher yields of γ-carboline 1. The
yields of carboline 1 are slightly higher when using microwave irradiation (methods C and F) than under
thermal conditions (methods A and D). We should note that attempts to carry out the Graebe-Ullmann reaction
in paraffin (methods B and E) gave 4-(4-methylphenyl)aminopyridine (6) as a side product. Both raising the
temperature and increasing the thermolysis time to 1 h lead to tar formation and a decrease in the yield of
γ-carboline 1 without significant effect on the ratio of carboline 1 and aminopyridine 6. Such a discrepancy in
the yields of 8-methyl-γ-carboline (1) in PPA and in paraffin may be attributed to a difference in the
mechanisms for the Graebe-Ullmann reaction in different media. Kalinowski et al. [10] proposed that the
reaction in PPA proceeds as an intramolecular electrophilic substitution in the aromatic ring by the action of an
aryl or hetaryl cation.
N
N
N
Me
+
+
NH
N
PPA

PPA
–H+
1
3
N
–N2
H
Me
However, such protonation is impossible in paraffin, and the biradical mechanism described by
Katritzky et al. [11] is therefore more likely.
Me
Me
Me
N
C
H
N
C
HC

3
N
–N2
N
N
N
~H· from
paraffin
~H+
1
6
The formation of para-tolylaminopyridine 6 may be explained in the framework of this mechanism by
the reduction of the biradical formed in the thermolysis of triazolopyridine 3 due to transfer of the radical chain
reaction to paraffin molecules.
In order to obtain further isomeric unsubstituted aza-γ-carbolines, we attempted to extend this reaction
to 1H-1,2,3-triazolo[4,5-c]pyridines 11a-c, which contain isomeric pyridyl substituents at the atom N(1). For the
synthesis of triazolopyridines 11a-c, we selected a scheme previously used for the preparation of
triazolopyridine 3 from 4-chloro-3-nitropyridine (8) and isomeric aminopyridines, which involves the
preparation of nitropyridines 12a-c and their reduction to aminopyridines 13a-c with subsequent diazotation.
NO2
H
N
Na2S2O4
H2O–EtOH
NH2
Z
, 10–15 min
Y
X
8
+
, 3.5 h
87–91%
X
Z
32–65%
N
Y
12a–c
N
N
N
NH2
N
H
N
NaNO2, 6 N HCl
0–5°C
Z
Y
94–95%
N
Z
X
13a–c
Y
11a–c
X
a X = N, Y = Z = CH; b X = Z = CH, Y = N; с X = Y = CH, Z = N
1238

The procedure for the synthesis of nitropyridine 9 proved inapplicable to aminopyridines since, instead
of the formation of dipyridylamines 12a-c upon heating in acetonitrile at reflux, tar is formed in the case of
3-aminopyridine, while the quaternary salt 14a is formed when using 4-aminopyridine. Under analogous
conditions, salt 14b is formed from 2-chloro-3-nitropyridine. In the case of 2-aminopyridine, there is no reaction
and only the starting compounds are isolated.
NO2
NH2
NH2
N
Cl
Cl
NH2
N
NO2
N+
i-Pr2EtN
8, i-Pr2EtN
MeCN, , 5 h
N+
Cl
14b
MeCN, , 5 h
88%
N
N
84%
NO2
14a
The explanation of this result may be that the endocyclic nitrogen atom in all the isomeric
aminopyridines is the more nucleophilic and basic site. This atom will act as a nucleophile under the given
reaction conditions, i.e., kinetic control will prevail at 80°C. On the other hand, the result of carrying out the
reaction under thermodynamic control conditions at ~150-170°C is nucleophilic substitution at the exocyclic
amino group to give nitropyridines 12a-c. This hypothesis is supported by literature reports that nitropyridines
12b [12] and 12c [13] are obtained in low yield by fusion of 4-chloropyridine 8 with two equivalents of the
corresponding aminopyridines. However, in addition to nitropyridines 12b,c, side products such as 4-amino-
3-nitropyridine are also formed under these conditions. Bacon and Hamilton [12] proposed that the formation of
such side products results from thermal decomposition of the desired products 12b,c. In our view, the formation
of some amount of 4-amino-3-nitropyridine may be attributed to the hydrolysis of salt 14a with opening of the
quaternized pyridine ring upon treatment of the reaction mixture with water. Furthermore, we may assume that
the appearance of nitropyridine 12a may occur through the intermediate formation of pyridinium chloride 14a,
in which aromatic nucleophilic substitution occurs by the action of the second equivalent of 4-aminopyridine to
give the nitropyridine 12a as the thermodynamically favored product. This hypothesis is supported by the
finding that the salt 14a does not undergo any change upon heating with one equivalent of 4-aminopyridine in
acetonitrile at reflux (~80°C), while nitropyridine 12a is formed in 70% yield upon heating in DMF at reflux
(150-160°C).
NH2
H2N
DMF
MeCN
, 2 h
12а
(70%)
12a
14a
+
+
, 2 h
N ·HCl
N
The preparation of nitropyridines 12a-c by fusing chloropyridine 8 and the corresponding
aminopyridines is inefficient, because an additional equivalent of the valuable aminopyridine is consumed, and
there is a large amount of tar formed, which substantially complicates the isolation and purification of the
desired products. Furthermore, the formation of nitropyridines 12a-c is an exothermic reaction, thus it is very
important to provide efficient stirring and to prevent overheating of the reaction mixture when significant
amounts of the starting compounds are used (5-10 g).
An alternative for the synthesis of nitropyridine 12a is the mononitration of 4-(4-pyridylamino)pyridine
(15) obtained by fusing 4-aminopyridine and 4-chloropyridine hydrochlorides. However, this approach is
inapplicable for the preparation of nitropyridines 12b,c from the corresponding asymmetric dipyridylamines,
since the nitration would proceed nonselectively and lead to a mixture of different nitro derivatives.
1239

HNO3 (fuming)
H2SO4 (conc.)
120°С, 1 h
N
220–230°C
2 h
H2N
Cl
N
12а
+
86%
N
N
·HCl
·HCl
44%
N
H
15
Aminopyridines 13a-c were obtained using sodium hydrosulfite, which is quite convenient and effective
reducing agent, giving yields of 87-91% for up to 3 g of nitropyridines 12a-c. In case of larger amounts of the
starting compound, the best method is catalytic hydrogenation over palladium in an acidic medium, which
proceeds quantitatively, since the aminopyridines 13a-c form salts under these conditions and do not inhibit the
catalyst; the yield is 90-96% upon isolation of the free bases.
Triazolo[4,5-c]pyridines 11a-c, obtained by diazotation of the aminopyridines 13a-c, were subjected to
thermal decomposition in PPA and decomposition using microwave irradiation, in order to obtain aza-
γ-carbolines 16a-d. The results and conditions of the Graebe-Ullmann reaction in PPA for triazolopyridines
11a-c are given in Table 3.
We should note that there have been repeated attempts to obtain aza-γ-carbolines 16a,c by the Graebe-
Ullmann reaction. Thus, Bremer [3] reported the first unsuccessful attempt to prepare 6-aza-γ-carboline (16c) by
the thermal decomposition of triazole 11c at 320°C in paraffin, while Kalinowski et al. [10] later reported that
thermolysis of triazole 11c in PPA also gave negative results.
The reports concerning the preparation of 8-aza-γ-carboline (16a) have been rather contradictory.
Koenigs [13] found that the thermolysis of triazolopyridine 11a in PPA or paraffin at 320°C leads to
diazacarbazole 16a in ~60% yield, while Kalinowski et al. [10] reported the preparation of a mixture of
carboline 16a (23%) and hydroxypyridylamine 17a (38%) under analogous conditions.
N
N
N
N
OH
N
Y'
N
X
Y
PPA
X
Y
+
220–230°С, 10 min
or
MW 170 W, 3 min
N
N
H
Z
Z
Z
H
Y
16a–d
17a–c
X
11a–c
a X = N, Y(Y') = Z = CH; b X = Y' = Z = CH, Y = N;
с X = Y(Y') = CH, Z = N; d X = Y = Z = CH, Y' = N
TABLE 3. Conditions and Results from the Preparation of Aza-
γ-carbolines 16a-d by the Graebe-Ullmann Reaction
Thermal conditions
Microwave irradiation
MW 170 W, 3 min,
method C (yield, %)
Starting
compound
310–320°С, 5 min,
220–230°С, 10 min,
method А (yield, %)
method B (yield, %)
16а (58)
16а (69)
16а (30), 17а (44)
16b (11)*, 16d (10)*,
17b (52)
16c (33)*2
11а
16b (11)*, 16d (13)*,
17b (52)
16c (24)*2
16b (27)*, 16d (34)*,
17b (52)
11b
16c (44), 17c (47)
11c
_______
*The yield was found from the ratio of compounds16b and 16d in 1H NMR spectral data.
*22-Aminopyridine and 1H-pyridin-2-one were also found among the products.
We previously reported [14] obtaining 5H-pyrido[3',4':4,5]pyrrolo[3,2-c]pyridine (16a) in 58% yield by
thermolysis of the triazole 11a in PPA for 5 min at 320°C[14], while the yield was raised to 69% when the
reaction was carried out at 220-230°C for 10 min. The major reaction product using microwave irradiation was
3-hydroxy-4-(4-pyridylamino)pyridine (17a), while the yield of carboline 16a was only 30%.
1240

Despite the report that the thermolysis of 2-pyridyltriazolopyridines in PPA does not lead to the
formation of diazacarbazoles, but rather to hydroxy derivatives such as 17c or dipyridylamine [10], we were
able to convert triazolo[4,5-c]pyridine 11c into 6-aza-γ-carboline (16c) both by thermolysis and microwave
irradiation. We should note that the major product of the Graebe-Ullmann reaction at 220°C is hydroxy
derivative 17c (47%), while the yield of carboline 16c is 44%. The yield of carboline 16c at 320°C drops to
24%, while 2-aminopyridine and other decomposition products were found in the reaction mixture by GC-MS.
The reduced yield of 6-aza-γ-carboline (16c) at 320°C may be attributed to thermal decomposition since this
compound in its base form melts with decomposition already at ~240°C.
More complex behavior is expected when using triazolopyridine 11b, since the formation of a mixture
of 7-aza- (16b) and 9-aza-γ-carbolines (16d) is possible in this case. Indeed, the decomposition of
triazolopyridine 11b both under thermal conditions and upon microwave irradiation leads to the formation of
both carbolines 16b,d, as well as 3-hydroxypyridine 17b. The major reaction product upon thermolysis at
320°C and upon microwave irradiation is the hydroxypyridine 17b (52%), while aza-γ-carbolines 16b,d are
formed in yields of only about 10% (Table 3). The yield of aza-γ-carbolines 16b,d is significantly enhanced to
27% and 34%, respectively, upon the decomposition of triazolopyridine 11b at 220-230°C, while the yield of
hydroxypyridine 17b is reduced to 35%. Azacarbolines 16b,d have very similar chromatographic mobility, and
are isolated as a mixture. However, we were able to isolate analytical samples of azacarbolines 16b,d as pure
compounds by using preparative thin-layer chromatography. All these findings indicate a low preparative value
of the Graebe-Ullmann reaction for obtaining 5H-pyrido[3',4':4,5]pyrrolo[2,3-c]- (16b) and 5H-pyrido-
[3',4':4,5]pyrrolo[3,2-b]pyridines (16d), and the need to develop other methods for the synthesis of these
compounds.
We decided to use an alternative method for the preparation of 6-aza-γ-carboline (16c) based on the
decomposition of 3-(4-pyridyl)-3H-1,2,3-triazolo[5,4-b]pyridine (18) under both thermal and microwave
irradiation conditions. Triazolopyridine 18 was obtained according to the following scheme entailing the
formation of nitropyridine 19 from 2-chloro-3-nitropyridine and 4-aminopyridine, the subsequent reduction of
intermediate 19 to aminopyridine 20, and diazotation.
Na2S2O4
NO2
EtOH–H2O, 
190°C
10 min
NH2
NO2
NH2
(92%)
N
+
N
NH
N
or
N
63%
H2, Pd/C, EtOH
N
N
H
N
Cl
(90%)
20
i-Pr2EtN
MeCN
, 5 h
19
84%
N
NaNO2
N
HCl
0–5°C
NH2
92%
NH2
N
NO2
DMF, , 3 h
N
N+
N
86%
Cl
N
14b
N
18
Both the thermolysis and microwave irradiation of triazolopyridine 18, which is isomeric to
triazolopyridine 11c, lead to the exclusive formation of hydroxypyridine 21 instead of the expected 9H-pyrido-
[3',4':4,5]pyrrolo[2,3-b]pyridine (16c).
1241

PPA
N
310–320°С, 5 min (56%)
220–230°С, 10 min (72%)
OH
N
18
MW 170 W, 3min (76%)
N
N
H
N
N
H
21
16c
Thus, we are the first to report the preparation of isomeric 6-, 7-, and 9-aza-γ-carbolines by the Graebe-
Ullmann reaction under both thermolysis and microwave irradiation conditions and establish that the direction
of this reaction depends substantially both on the conditions and structure of the starting triazolopyridines.
Furthermore, we are the first to obtain previously unreported 5H-pyrido[3',4':4,5]pyrrolo[2,3-c]pyridine (7-aza-
γ-carboline) and 5H-pyrido[3',4':4,5]pyrrolo[3,2-b]pyridine (9-aza-γ-carboline).
EXPERIMENTAL
1
The H NMR and 13C NMR spectra using APT were recorded on a Bruker Avance-400 spectrometer
(400 and 100 MHz, respectively). The signals of the residual solvent protons served as standard: 7.27 ppm for
CDCl3, 2.51 ppm for DMSO-d6 in the 1H NMR spectra and 71.1 ppm for CDCl3 and 39.5 ppm for DMSO-d6 in
the 13C NMR spectra. The electron impact mass spectra were recorded on a Finnigan MAT ITD-700 mass
spectrometer at 70 eV for mass range m/z 45-400. The combined chromato-mass-spectral studies of the reaction
mixtures and isolated products were carried out using a Shimadzu Analytical HPLC SCL10Avp liquid
chromatograph and PE SCIX API 150 mass spectrometer with electrospray and positive ionization. The
elemental analysis was carried out on an Elemental Analyzer Euro EA CHNS-analyzer. The melting points were
measured in open capillaries and were not corrected. The course of the reactions and purity of the products
obtained were followed by thin-layer chromatography on Silufol UV-254 plates using 2:1 EtOAc–MeOH as the
eluent. A Funai MO785VT household microwave oven was used for carrying out the reactions with microwave
irradiation.
Hydrochloride salt of N-(4-pyridyl)pyridinium chloride was obtained according to Koenigs [15].
Yield 68%. Fine cream-colored crystals, mp 162–163°С (EtOH) (mp 151-152°С (modification I) and 172174°С
1
(modification II) from MeOH [15]). Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 8.08 (2Н, dd, J = 4.7,
J = 1.5, H-3',5'); 8.39 (2Н, dd, J = 7.8, J = 6.5, H-3,5); 8.88 (1Н, t, J = 7.8, Н-4); 9.03 (2Н, dd, J = 4.7, J = 1.5,
H-2',6'); 9.48 (2Н, d, J = 6.5, Н-2,6).
4-(4-Methylphenyl)aminopyridine (6) was obtained according to Jerchel [16]. Yield 79%. Light-gray
1
crystals, mp 198-199°С (MeOH–H2O) (mp 198°С (MeOH–H2O) [16]). Н NMR spectrum (CDCl3), δ, ppm (J,
Hz): 2.22 (3H, s, CH3); 6.68 (2H, dd, J = 4.7, J = 1.5, Н-3,5); 6.98 (2H, d, J = 8.3, Н-2',6'); 7.04 (2H, d, J = 8.3,
Н-3',5'); 7.19 (1H, br. s, NH); 8.09 (2H, dd, J = 4.7, J = 1.5, Н-2,6).
4-(4-Methyl-2-nitrophenyl)aminopyridine (5). A suspension of aminopyridine 6 (7.5 g, 41.0 mmol)
in 14.3% nitric acid (1.08 g/ml) (60 ml) was heated for 1 h at 85-90°C. The precipitate dissolved, and the
solution turned red-brown. Upon cooling, the reaction mixture was brought to pH 8.5-9.0 by adding ammonium
hydroxide with vigorous stirring. The precipitate formed was filtered off, washed with ice water, and
recrystallized from 75% ethanol. Yield 7.8 g (84%). Yellow-orange crystals, mp 136-137°С. 1Н NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.37 (3Н, s, СН3); 7.07 (2H, dd, J = 4.7, J = 1.5, Н-3,5); 7.36 (1H, dd, J = 8.6, J = 1.7,
Н-5'); 7.51 (1H, d, J = 8.6, Н-6'); 8.01 (1H, d, J = 1.7, Н-3'); 8.46 (2H, dd, J = 4.7, J = 1.5, Н-2,6); 9.08 (1H, br. s,
NH). 13С NMR spectrum (CDCl3), δ, ppm: 20.5 (CH3); 113.6 (C-3,5); 118.9 (C-6'); 126.5 (C-3'); 131.3 (C-4');
136.0 (C-2'); 136.6 (C-5'); 147.5 (C-1'); 151.09 (C-4); 151.13 (C-2,6). Found, %: С 62.64; Н 4.71; N 18.22.
C12H11N3O2. Calculated, %: С 62.87; Н 4.84; N 18.33.
4-(4-Methyl-2,6-dinitrophenyl)aminopyridine (7) was obtained from aminopyridine 6 by analogy to
the nitro derivative 5. Nitration was carried out with 42% nitric acid (1.25 g/ml) for 1 h at 60-65°C. Yield 65% .
1
Yellow-brown crystals, mp 173-174°С (EtOH). Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.50 (3Н, s, CH3);
1242

6.72 (2H, dd, J = 4.7, J = 1.6, Н-3,5); 8.12 (2H, s, Н-3',5'); 8.41 (2H, dd, J = 4.7, J = 1.6, Н-2,6); 8.66 (1H, br. s,
NH). 13C NMR spectrum, δ, ppm: 20.6 (CH3); 111.5 (C-3,5); 128.6 (C-4'); 131.8 (C-3',5'); 132.9 (C-2',6'); 142.5
(C-1'); 147.6 (C-4); 151.0 (C-2,6). Found, %: С 52.50; Н 3.70; N 20.37. C12H10N4O4. Calculated, %: С 52.56;
Н 3.68; N 20.43.
4-Hydroxy-3-nitropyridine was obtained by the nitration of 4-hydroxypyridine according to Kruger
1
[17]. Yield 92%. Fine lemon colored crystals, mp 279-280°С (H2O) (mp 278-279°C (H2O) [17]). Н NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 6.48 (1Н, d, J = 7.5, H-5); 7.77 (1Н, dd, J = 7.5, J = 1.4, H-6); 8.79 (1Н, d,
J= 1.4, H-2); 12.30 (1Н, br. s, ОН).
4-Chloro-3-nitropyridine (8) was obtained from 4-hydroxy-3-nitropyridine by the action of PCl5–
POCl3 according to Houston et al. [18]. Yield 95%. Orange oil, which crystallized upon standing, mp 43-44°С
(mp 43-45°С [18]). 1Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.56 (1Н, d, J = 5.4, H-5); 8.72 (1Н, d, J = 5.4,
H-6); 9.15 (1Н, s, H-2).
4-(4-Methylphenyl)amino-3-nitropyridine (9). A solution of 4-chloro-3-nitropyridine (8) (4.6 g, 29.0
mmol) in acetonitrile (10 ml) was added dropwise with vigorous stirring to a solution of p-toluidine (3.1 g, 29.0
mmol) and diisopropylethylamine (5.1 ml, 29.2 mmol) in acetonitrile (20 ml), and the mixture was heated at
reflux for 5 h. The reaction mixture was evaporated. The residue was dissolved in methylene chloride (100 ml)
and washed two or three times with aqueous potassium carbonate. The organic layer was dried over sodium
sulfate and evaporated to dryness. The residue was recrystallized from aqueous ethanol. Yield 5.4 g (82%).
Yellow-brown crystals, mp 121-122°С (mp 123°С [19]). 1Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.42 (3Н,
s, СН3); 6.89 (1H, d, J = 6.1, H-5); 7.17 (2H, d, J = 8.2, H-3',5'); 7.29 (2H, d, J = 8.2, H-2',6'); 8.23 (1Н, d,
J = 6.1, Н-6); 9.28 (1Н, s, H-2); 9.61 (1Н, br. s, NH). 13С NMR spectrum (CDCl3), δ, ppm: 21.1 (CH3); 109.2 (C-5);
125.5 (C-2',6'); 130.0 (C-4'); 130.6 (C-3',5'); 133.8 (C-3); 137.5 (C-1'); 147.9 (C-4); 149.1 (C-2); 153.1 (C-6). Found,
%: С 63.07; Н 4.76; N 18.23. C12H11N3O2. Calculated, %: С 62.87; Н 4.84; N 18.33.
Reduction of Nitro Derivatives 5 and 9 (General Method). Na2S2O4 (19.2 g, 110.0 mmol) was added
to a suspension of nitro derivative 5 or 9 (7.0 g, 31.0 mmol) in ethanol (70 ml) and water (30 ml), and the
mixture was heated at reflux for 3.5 h with vigorous stirring. After cooling, concentrated hydrochloric acid (40
ml) was added carefully to the reaction mixture, and it was heated at reflux for an additional 30 min. The
precipitate formed was filtered off and washed with a small amount of hot water. The filtrate was evaporated to
about 30 ml, brought to pH ~10 by adding ammonium hydroxide, and extracted with CH2Cl2 (4×70 ml). The
extract was dried over anhydrous sodium sulfate and evaporated to dryness.
4-(2-Amino-4-methylphenyl)aminopyridine (4). Yield 5.5 g (89%). Light-beige crystals, mp
1
144-145°С. Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.31 (3Н, s, СН3); 3.74 (2H, br. s, NH2); 5.62 (1H, br. s,
NH); 6.52 (2H, d, J = 6.4, H-3,5); 6.61 (1H, dd, J = 7.9, J = 1.2, Н-5'); 6.67 (1H, d, J = 1.2, Н-3'); 7.00 (1H, d,
J = 7.9, Н-6'); 8.24 (2H, d, J = 6.4, H-2,6). 13С NMR spectrum (CDCl3), δ, ppm: 21.2 (CH3); 108.8 (C-3,5); 116.9
(C-6'); 119.9 (C-3'); 122.1 (C-4'); 127.4 (C-5'); 138.0 (C-2'); 143.0 (C-1'); 150.2 (C-2,6); 152.3 (C-4). Found, %:
С 72.32; Н 6.40; N 20.90. C12H13N3. Calculated, %: С 72.34; Н 6.58; N 21.09.
3-Amino-4-(4-methylphenyl)aminopyridine (10). Yield 5.7 g (92%). Light-brown crystals, mp
165-166°С. 1Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.36 (3Н, s, СН3); 3.35 (2H, br. s, NH2); 5.95 (1H, br.
s, NH); 6.94 (1H, d, J = 5.5, H-5); 7.03 (2H, d, J = 8.0, H-3',5'); 7.17 (2H, d, J = 8.0, H-2',6'); 7.94 (1Н, d, J = 5.5,
Н-6); 8.05 (1Н, s, H-2). 13С NMR spectrum (CDCl3), δ, ppm: 20.8 (CH3); 108.2 (C-5); 122.0 (C-2',6'); 130.8
(C-4'); 131.0 (C-3',5'); 133.0 (C-3); 137.8 (C-1'); 138.5 (C-2); 141.3 (C-4); 142.7 (C-6). Found, %: С 72.09;
Н 6.75; N 20.98. C12H13N3. Calculated, %: С 72.34; Н 6.58; N 21.09.
Diazotation of Aminopyridines 4 and 10 (General Method). Water (15 ml) was added with stirring to
a suspension of diamine 4 or 10 (5.0 g, 25.0 mmol) in concentrated hydrochloric acid (15 ml) and cooled to
0°C. Then, a solution of NaNO2 (1.81 g, 26.0 mmol) in water (3 ml) was added dropwise to the mixture with
ice water cooling, maintaining the temperature of the reaction mixture at 0-5°C. The obtained mixture was
stirred for an additional 1 h at 20-25°, neutralized by adding ammonium hydroxide, and filtered. The precipitate
was washed with ice water and dried in air.
1243

5-Methyl-1-(4-pyridyl)-1H-1,2,3-benzotriazole (2). Yield 4.8 g (91%). Light-beige crystals, mp
195-197°С (decomp.). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.53 (3Н, s, СН3); 7.58 (1Н, dd, J = 8.6, J
= 1.2, Н-6); 8.01-8.05 (3Н, m, Н-4,3',5'); 8.08 (1Н, d, J = 8.6, Н-7); 8.85 (2Н, d, J = 6.2, Н-2',6'). 13С NMR
spectrum (DMSO-d6), δ, ppm: 21.3 (CH3); 111.5 (C-7); 115.7 (C-3',5'); 119.4 (C-4); 123.0 (C-5); 131.7 (C-6);
135.5 (C-7a); 143.6 (C-4'); 147.2 (C-3a); 152.1 (C-2',6'). Mass spectrum, m/z (Irel, %): 210 [M]+ (21), 182 [M-
N2]+ (35), 181 (86), 154 (3), 127 (3), 104 (9), 78 [Py]+ (56), 77 (16), 63 (9), 52 (16), 51 (100), 50 (27), 39 (14).
Found, %: С 68.70; Н 4.81; N 26.60. C12H10N4. Calculated, %: С 68.56; Н 4.79; N 26.65.
1-(4-Methylphenyl)-1H-1,2,3-triazolo[4,5-c]pyridine (3). Yield 5.0 g (96%). Light-brown crystals,
mp 152-153°С. 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.46 (3Н, s, СН3); 7.52 (2Н, d, J = 8.4, Н-3',5');
7.79 (2Н, d, J = 8.4, Н-2',6'); 7.95 (1H, dd, J = 5.9, J = 1.2, Н-6); 8.66 (1Н, d, J = 5.9, Н-7); 9.61 (1Н, d, J = 1.2,
13
H-4). С NMR spectrum (DMSO-d6), δ, ppm: 21.2 (CH3); 106.4 (C-7); 123.2 (C-2',6'); 131.0 (C-3',5'); 133.8 (C-
4'); 135.8 (C-7a); 139.6 (C-1'); 143.8 (C-3a); 144.8 (C-6); 146.2 (C-4). Mass spectrum, m/z (Irel, %): 210 [M]+ (9),
182 [M-N2]+ (45), 181 (100), 167 (3), 154 (4), 140 (2), 91 [Bn]+ (21), 89 (4), 77 (3), 65 (34), 51 (10), 50 (7), 39
(18). Found, %: С 68.67; Н 4.75; N 26.70. C12H10N4. Calculated, %: С 68.56; Н 4.79; N 26.65.
8-Methyl-5H-pyrido[4,3-b]indole (8-Methyl-γ-carboline) (1). A. A mixture of benzotriazole 2 (0.42
g, 2.0 mmol) and PPA (2.50 g) obtained according to Uhlig [20] was heated to 220°C and maintained at this
temperature for 5-10 min. Upon cooling, the reaction mixture was dissolved in water (10 ml) and neutralized by
adding ammonium hydroxide. The precipitate formed was filtered off, washed with cold water, and
recrystallized from aqueous ethanol. Yield 0.21 g (58%). Fine light-gray crystals, mp 243-244°С (mp 244°С
1
(EtOH–H2O) [6]). Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.48 (3Н, s, СН3); 7.31 (1Н, dd, J = 8.2,
J = 1.7, Н-7); 7.42 (1Н, dd, J = 5.7, J = 0.9, Н-3); 7.45 (1Н, d, J = 8.2, H-6); 8.02 (1Н, d, J = 1.7, H-9); 8.39
(1Н, d, J = 5.7, Н-4); 9.28 (1Н, d, J = 0.9, Н-1); 11.58 (1Н, br. s, NH). 13С NMR spectrum (DMSO-d6), δ, ppm:
21.5 (СН3); 106.9 (С-4); 111.6 (С-6); 119.7 (С-9b); 120.8 (С-7); 121.4 (С-9а); 128.4 (С-9); 129.3 (С-5а); 138.2
(С-8); 143.0 (С-3); 144.2 (С-4а); 144.7 (С-1). Mass spectrum, m/z (Irel, %): 182 [M]+ (100), 181 (68), 154 [M-
HCN]+ (3), 127 (4), 91 (4), 77 (6), 63 (5), 52 (5), 51 (6), 39 (5). Found, %: С 79.32; Н 5.64; N 15.26. C12H10N2.
Calculated, %: С 79.10; Н 5.53; N 15.37.
B. A mixture of benzotriazole 2 (0.42 g, 2.0 mmol) and paraffin (2.00 g) was maintained at 340-350°C
for 10 min in an inert atmosphere. Upon cooling, the reaction mixture was diluted with benzene (20 ml), and
3 N hydrochloric acid (10 ml) was added. The aqueous layer was separated, washed with petroleum ether (2×10 ml),
and made basic by adding ammonium hydroxide. The precipitate formed was washed with cold water, and air
1
dried to give 0.27 g fine crystalline light-beige product mixture, which was shown by H NMR spectroscopy to
consist of carboline 1 (44% relative to triazole 2) and aminopyridine 6 (28% relative to triazole 2).
C. A mixture of benzotriazole 2 (0.42 g, 2.0 mmol) and PPA (2.5 g) was thoroughly mixed and
maintained in a microwave oven for 5 min at 170 W irradiation power. The reaction mixture was treated as in
method A. Yield 0.24 g (67%). Fine, light-beige crystals, mp 242-243°C (EtOH–H2O).
D. By analogy to the method A, but using triazolopyridine 3 (0.42 g, 2.0 mmol), which was heated at
250°C. Yield 0.24 g (66%), mp 243-244°C.
E. By analogy to the method B, but using triazolopyridine 3 (0.42 g, 2.0 mmol), which was heated at 360-
370°C for 10 min, we obtained 0.29 g fine crystalline light-beige product mixture. 1H NMR spectroscopy indicated
that the product contained carboline 1 (48% relative to triazole 3) and aminopyridine 6 (32% relative to triazole 3).
F. By analogy to the method C, but using triazolopyridine 3 (0.42 g, 2.0 mmol). Yield 0.26 g (72%), mp
242-243°C.
Nitro(pyridylamino)pyridines 12a-c and 19 (General Method). A. A solution of 4-chloro-3-nitro-
pyridine 8 or 2-chloro-3-nitropyridine (4.72 g, 29.8 mmol) in acetonitrile (10 ml) was added dropwise with
vigorous stirring to a solution of 4-aminopyridine (2.80 g, 29.8 mmol) and diisopropylethylamine (5.20 ml,
29.8 mmol) in acetonitrile (20 ml), and the mixture was heated at reflux for 5 h. The reaction mixture was
evaporated to a small volume. The precipitate formed was filtered off, washed with a small amount of benzene,
and dried in air.
1244

B. A mixture of 4-chloro-3-nitropyridine (8) or 2-chloro-3-nitropyridine (3.17 g, 20.0 mmol) and the
corresponding aminopyridine (3.76 g, 40.0 mmol) was heated to 150-170°C (spontaneous heating was
observed) and maintained at or below 190°C for 10 min. The cooled reaction mixture was dissolved in 2 N
hydrochloric acid (40 ml), evaporated to about 10 ml, made basic by adding 25% ammonium hydroxide, and
extracted with CH2Cl2 (5×30 ml). The extract was dried over anhydrous sodium sulfate, evaporated to dryness,
and subjected to chromatography on silica gel using 15:1 EtOAc–MeOH as the eluent. The residue was
recrystallized from water and dried in air.
3-Nitro-4-(4-pyridylamino)pyridine (12a) was obtained using the method B from 4-chloro-3-nitro-
pyridine (8) and 4-aminopyridine. Yield 1.94 g (45%). Light-yellow crystals, mp 118-119°С (H2О) (mp
1
122-123°С (H2O) [21]). Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.24 (2Н, d, J = 6.2, Н-3',5'); 7.34 (1Н, d,
J = 6.0, Н-5); 8.47 (1Н, d, J = 6.0, Н-6); 8.68 (2Н, d, J = 6.2, H-2',6'); 9.37 (1Н, s, H-2); 9.73 (1Н, br. s, NH).
13С NMR spectrum (CDCl3), δ, ppm: 109.8 (С-5); 116.9 (С-3',5'); 131.5 (С-3); 144.7 (С-4); 145.0 (С-4'); 149.3
(6-СН); 151.7 (С -2',6'); 154.1 (С-2). Found, %: С 55.65; Н 3.91; N 25.76. C10H8N4О2. Calculated, %: С 55.56;
Н 3.73; N 25.91.
The first chromatographic fraction gave 4-amino-3-nitropyridine. Yield 0.70 g (25%). Light-yellow
1
crystals, mp 200-201°C (water) (mp 198-200°C [12], mp 202-204°C [22], mp 225-226°C [23]). The H NMR
spectrum corresponded to the data of Antoine et al. [23].
3-Nitro-4-(3-pyridylamino)pyridine (12b) was obtained using the method B from 4-chloro-3-nitro-
pyridine (8) and 3-aminopyridine. Yield 1.38 g (32%). Yellow-orange crystals, mp 159-160°С (H2О) (mp
161°С (CH2Cl2–Et2O–petroleum ether) [12]). 1Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 6.87 (1Н, d, J = 6.1,
Н-5); 7.43 (1Н, dd, J = 8.1, J = 4.7, Н-5'); 7.65 (1Н, ddd, J = 8.1, J = 2.4, J = 1.3, Н-4'); 8.30 (1Н, d, J = 6.1,
Н-6); 8.58 (1Н, dd, J = 4.7, J = 1.3, Н-6'); 8.61 (1Н, d, J = 2.4, H-2'); 9.29 (1Н, s, H-2); 9.63 (1Н, br. s, NH). 13С
NMR spectrum (CDCl3), δ, ppm: 108.9 (С-5); 124.5 (С-5'); 133.0 (С-4'); 133.6 (С-3); 147.2 (С-2'); 147.4 (С-4);
148.6 (С-6'); 149.3 (С-6); 152.9 (С-3'); 153.9 (С-2). Found, %: С 55.41; Н 3.80; N 25.95. C10H8N4О2.
Calculated, %: С 55.56; Н 3.73; N 25.91.
3-Nitro-4-(2-pyridylamino)pyridine (12c) was obtained using the method B from 4-chloro-3-nitro-
pyridine (8) and 2-aminopyridine. Yield 2.20 g (51%). Bright yellow crystals, mp 130-131°С (H2О) (mp
1
131-132°С (H2O) [3]). Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.05 (1Н, d, J = 8.2, Н-3'); 7.12 (1Н, dd,
J = 7.1, J = 4.8, Н-5'); 7.75 (1Н, ddd, J = 8.2, J = 7.1, J = 1.9, Н-4'); 8.46 (1Н, dd, J = 4.8, J = 1.9, Н-6'); 8.52
(1Н, d, J = 6.1, Н-5); 8.83 (1Н, d, J = 6.1, H-6); 9.38 (1Н, s, H-2); 10.41 (1Н, br. s, NH). 13С NMR spectrum
(CDCl3), δ, ppm: 112.5 (С-5); 115.0 (С-3'); 119.6 (С-5'); 131.0 (С-3); 138.6 (С-4'); 144.3 (С-4); 148.2 (С-6');
148.7 (С-6); 152.5 (С-2'); 154.2 (С-2). Found, %: С 55.41; Н 3.95; N 25.79. C10H8N4О2. Calculated, %:
С 55.56; Н 3.73; N 25.91.
3-Nitro-2-(4-pyridylamino)pyridine (19) was obtained using the method B from 2-chloro-3-nitro-
pyridine and 4-aminopyridine. Yield 2.72 g (63%). Yellow-brown crystals, mp 165-166°С (H2О) (mp 165-167°С
1
[24]). Н NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.03 (1Н, dd, J = 8.2, J = 4.7, Н-5); 7.75 (2Н, d, J = 5.4,
Н-3',5'); 8.56 (2Н, d, J = 5.4, Н-2',6'); 8.59-8.62 (2Н, m, Н-4,6); 10.28 (1Н, br. s, NH). 13С NMR spectrum
(CDCl3), δ, ppm: 114.9 (С-3',5'); 115.7 (5-СН); 119.8 (С-3); 124.7 (С-2); 135.6 (С-4); 149.2 (С-4'); 150.7
(С-2',6'); 154.6 (С-6). Found, %: С 55.51; Н 3.68; N 25.92. C10H8N4О2. Calculated, %: С 55.56; Н 3.73; N 25.91.
4-Amino-1-(3-nitropyridin-4-yl)pyridinium chloride (14a) was obtained using the method A from
4-chloro-3-nitropyridine (8) and 4-aminopyridine. Yield 4.40 g (88%). Light orange crystals, mp 266-267°С
1
(decomp.). Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.09 (2H, d, J = 6.8, Н-3',5'); 8.06 (1H, dd, J = 5.2,
J = 1.0, Н-5); 8.38 (2Н, d, J = 6.8, Н-2',6'); 9.14 (2H, br. s, NH2); 9.21 (1Н, d, J = 5.2, Н-6); 9.55 (1Н, d, J = 1.0,
Н-2). 13С NMR spectrum (DMSO-d6), δ, ppm: 109.2 (С-3',5'); 123.7 (С-5); 139.2 (С-3); 142.0 (С-4);
142.5 (С-2',6'); 147.5 (С-2); 156.6 (С-6); 159.9 (С-4'). Found, %: С 47.75; Н 3.49; N 22.24. C10H9ClN4О2.
Calculated, %: С 47.54; Н 3.59; N 22.17.
1245

4-Amino-1-(3-nitropyridin-2-yl)pyridinium chloride (14b) was obtained using the method A from
2-chloro-3-nitropyridine and 4-aminopyridine. Yield 4.20 g (84%). Light-yellow crystals, mp 285-286°С
(decomp.). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.07 (2H, d, J = 7.7, Н-3',5'); 7.98 (1H, dd, J = 8.2,
J = 4.8, Н-5); 8.42 (2Н, d, J = 7.7, Н-2',6'); 8.86 (1H, dd, J = 8.2, J = 1.5, Н-4); 8.95 (1H, dd, J = 4.8, J = 1.5,
13
Н-6); 9.09 (2H, br. s, NH2). С NMR spectrum (DMSO-d6), δ, ppm: 109.0 (С-3',5'); 127.3 (С-5); 136.8 (С-4);
139.7 (С-3); 142.0 (С-2',6'); 144.9 (С-2); 153.7 (С-6); 160.2 (С-4'). Found, %: С 47.38; Н 3.65; N 22.30.
C10H9ClN4О2. Calculated, %: С 47.54; Н 3.59; N 22.17.
4-(4-Pyridylamino)pyridine (15). A mixture of 4-aminopyridine hydrochloride (2.7 g, 2.1 mmol) and
4-chloropyridine hydrochloride (3.0 g, 2.0 mmol) was heated to 230°C (bath temperature) and maintained at
220-230°C for 3 h. Upon cooling, the solid reaction mixture was dissolved in water (10 ml), made basic by
adding ammonium hydroxide, and filtered. The precipitate was recrystallized from a small amount of water and
dried in air. Yield 1.52 g (44%). Fine light-gray crystals, mp 273-274°С (Н2О) (mp 273-275°С (H2O) [21]).
1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.12 (4Н, d, J = 6.0, H-3,3',5,5'); 8.34 (4Н, d, J = 6.0,
Н-2,2',6,6'); 9.34 (1Н, br. s, NH). 13С NMR spectrum (DMSO-d6), δ, ppm: 111.7 (C-3,3',5,5'); 147.8 (С-4,4');
150.4 (C-2,2',6,6').
Alternative Methods for the Synthesis of 3-Nitro-4-(4-pyridylamino)pyridine (12a). C. A
suspension of the pyridinium chloride 14a (0.25 g, 1.0 mmol) and 4-aminopyridine (0.10 g, 1.1 mmol) in DMF
(2 ml) was heated at reflux for 2 h. Upon cooling, ammonium hydroxide (l ml) was added to the reaction
mixture, which was then evaporated to dryness. The residue was subjected to chromatography on silica gel
using 15:1 EtOAc–MeOH as the eluent. Yield 0.15 g (70%). Light-yellow crystals, mp 119-120°C. The
1H NMR spectrum was identical to the spectrum of the sample obtained using method B.
D. 4-(4-Pyridylamino)pyridine (15) (1.45 g, 8.5 mmol) was added in portions with vigorous stirring and
cooling to concentrated sulfuric acid (4.0 ml). Then, fuming nitric acid (ρ=1.51 g/cm3) (0.8 ml, 19.0 mmol) was
added to the resultant solution. The reaction mixture was maintained for 1 h at 110-120°C (bath temperature).
The obtained orange reaction mixture was poured onto ice and neutralized by adding ammonium hydroxide.
The precipitate formed was filtered off, washed with ice water, and dried in air. Yield 1.57 g (86%).
1
Light-yellow crystals, mp 119-120°C. The H NMR spectrum was identical to the spectrum of the sample
obtained using method B.
Amino(pyridylamino)pyridines 13a-c and 20 (General Method). A. Sodium hydrosulfite (3.13 g,
18.0 mmol) was added to a suspension of nitro compound 12a-c or 19 (1.08 g, 5.0 mmol) in ethanol (15 ml) and
water (5 ml), and the reaction mixture was heated at reflux for 3.5 h with vigorous stirring. Upon cooling,
concentrated hydrochloric acid (4 ml) was carefully added to the reaction mixture, which was heated at reflux
for an additional 30 min. The precipitate formed was removed by filtration through a paper or microporous glass
filter and washed with a small portion of hot water. The filtrate was evaporated to 3-4 ml, brought to pH ~10 by
adding ammonium hydroxide, cooled, and filtered. The precipitate was recrystallized from 1-2 ml water and
dried in air.
B. Concentrated hydrochloric acid (4 ml) and 10% Pd/C (0.13 g) were added to a solution of nitro
compound 12a-c or 19 (2.5 g, 11.6 mmol) in methanol (50 ml) and hydrogenated until hydrogen consumption
ceased (~0.8 liters). The reaction mixture was filtered, and the filtrate was evaporated to dryness. The residue
may be used for the subsequent preparation of triazolopyridines 11a-c or 18, assuming quantitative yield. In
order to isolate the free base, the residue was dissolved in water (5 ml), neutralized by the addition of
ammonium hydroxide, and cooled. The precipitate was filtered off and dried in air.
3-Amino-4-(4-pyridylamino)pyridine (13a). Yield 0.83 g (89%, method A), 2.07 g (96%, method B).
1
Light-gray crystals, mp 235-236°С (H2О) (mp 239°С (H2O) [21]). Н NMR spectrum (DMSO-d6), δ, ppm (J,
Hz): 5.66 (2Н, br. s, NH2); 7.08 (2Н, d, J = 6.8, Н-3',5'); 7.20 (1Н, d, J = 5.4, Н-5); 7.51 (1Н, br. s, NH); 7.84 (1Н,
13
d, J = 5.4, Н-6); 8.11 (1Н, s, H-2); 8.33 (2Н, d, J = 6.8, H-2',6'). С NMR spectrum (DMSO-d6), δ, ppm: 110.3
(С-3',5'); 114.9 (С-5); 131.9 (С-3); 137.0 (С-4); 137.9 (С-6); 138.2 (С-2); 149.6 (С-4'); 149.8 (С-2',6'). Found,
%: С 64.75; Н 5.37; N 30.23. C10H10N4. Calculated, %: С 64.50; Н 5.41; N 30.09.
1246

3-Amino-4-(3-pyridylamino)pyridine (13b). Yield 0.81 g (87%, method A), 1.94 g (90%, method B).
Light-beige crystals, mp 166-167°С (H2О). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 4.92 (2Н, br. s,
NH2); 6.91 (1Н, d, J = 5.5, Н-5); 7.26 (1Н, ddd, J = 8.3, J = 4.7, J = 0.7, Н-5'); 7.45 (1Н, ddd, J = 8.3, J = 2.8,
J = 1.3, Н-4'); 7.67 (1Н, d, J = 5.5, Н-6); 7.75 (1H, br. s, NH); 7.93 (1Н, s, H-2); 8.13 (1Н, dd, J = 4.7, J = 1.3,
13
Н-6'); 8.61 (1Н, dd, J = 2.8, J = 0.7, H-2'). С NMR spectrum (DMSO-d6), δ, ppm: 105.6 (С-5); 122.0 (С-4');
124.6 (С-5'); 130.3 (С-2'); 130.9 (С-6'); 135.0 (С-3); 135.6 (С-4); 143.5 (С-3'); 143.9 (С-6); 145.3 (С-2).
Found, %: С 64.71; Н 5.20; N 30.26. C10H10N4. Calculated, %: С 64.50; Н 5.41; N 30.09.
3-Amino-4-(2-pyridylamino)pyridine (13c). Yield 0.85 g (91%, method A), 1.98 g (92%, method B).
Dark-brown crystals, mp 147-148°С (H2О) (mp 148-149°С (H2O) [3]). 1Н NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 4.60 (2Н, br. s, NH2); 7.13 (1Н, ddd, J = 7.2, J= 5.0, J= 1.0, Н-5'); 7.24 (1Н, ddd, J = 8.3, J = 1.0, J = 0.8,
Н-3'); 7.76 (1Н, br. s, NH); 7.89 (1Н, ddd, J = 8.3, J = 7.2, J = 1.9, Н-4'); 8.11 (1Н, d, J = 5.4, Н-5); 8.26 (1Н, d,
J = 5.4, H-6); 8.44 (1Н, s, H-2); 8.55 (1Н, ddd, J = 5.0, J = 1.9, J= 0.8, Н-6'). 13С NMR spectrum (DMSO-d6), δ,
ppm: 110.1 (С-5); 114.6 (С-3'); 118.5 (С-5'); 122.6 (С-6); 129.6 (С-3); 135.4 (С-2); 138.2 (С-4'); 140.6 (С-4);
147.1 (С-6'); 153.8 (С-2'). Found, %: С 64.36; Н 5.59; N 29.97. C10H10N4. Calculated, %: С 64.50; Н 5.41;
N 30.09.
3-Amino-2-(4-pyridylamino)pyridine (20). Yield 0.86 g (92%, method A), 1.94 g (90%, method B).
1
Red-brown crystals, mp 200-201°С (EtOH) (mp 203-205°С (EtOH) [25]). Н NMR spectrum (CDCl3), δ, ppm
(J, Hz): 4.12 (2Н, br. s, NH2); 6.64 (1Н, dd, J = 7.8, J = 4.7, Н-5); 6.86 (1Н, dd, J = 7.8, J = 1.5, Н-4); 7.27 (2Н,
d, J = 6.4, Н-3',5'); 7.62 (1Н, dd, J = 4.7, J = 1.5, Н-6); 7.67 (1Н, br. s, NН); 8.14 (2Н, d, J = 6.4, Н-2',6'). 13С
NMR spectrum (CDCl3), δ, ppm: 111.2 (С-3',5'); 117.5 (С-5); 120.9 (С-4); 132.9 (С-3); 134.6 (С-6); 141.5
(С-4'); 148.7 (С-2); 149.0 (С-2',6'). Found, %: С 64.56; Н 5.26; N 30.06. C10H10N4. Calculated, %: С 64.50;
Н 5.41; N 30.09.
Triazolopyridines 11a-c and 18 (General Method). A solution of NaNO2 (0.37 g, 5.4 mmol) in water
(1 ml) was added dropwise with vigorous stirring to a solution of amino derivative 13a-c or 20 (0.75 g,
5.0 mmol) in 6 N hydrochloric acid (5 ml), while keeping the temperature of the reaction mixture in the range of
0-5°C. The mixture was then stirred for an additional 30 min at 20-25°C, neutralized by adding ammonium
hydroxide, and filtered. The precipitate was washed with ice water and dried in air.
1-(4-Pyridyl)-1H-1,2,3-triazolo[4,5-c]pyridine (11a). Yield 0.93 g (94%). Light-gray crystals, mp
181-182°С (Н2О) (mp 183°С (Н2О) [21]). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 8.07 (2Н, d, J = 5.5,
Н-3',5'); 8.24 (1Н, d, J = 4.6, Н-7); 8.76 (1Н, d, J = 4.6, Н-6); 8.89 (2Н, d, J = 5.5, H-2',6'); 9.65 (1Н, s, Н-4).
13С NMR spectrum (DMSO-d6), δ, ppm: 106.5 (С-7); 115.6 (С-3',5'); 134.9 (С-7а); 142.5 (С-4'); 143.2 (С-3а);
144.5 (С-6); 146.5 (С-4); 151.7 (С-2',6'). Mass spectrum, m/z (Irel, %): 197 [M]+ (6), 169 [M-N2]+ (34), 168 (10),
142 [169-HCN]+ (8), 118 (5), 115 (11), 88 (4), 78 (23), 64 (18), 52 (18), 51 (100), 50 (38), 38 (31). Found, %: С
60.89; Н 3.78; N 35.36. C10H7N5. Calculated, %: С 60.91; Н 3.58; N 35.51.
1-(3-Pyridyl)-1H-1,2,3-triazolo[4,5-c]pyridine (11b). Yield 0.93 g (94%). Light-pink crystals, mp
1
218-219°С (Н2О). Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.78 (1Н, dd, J = 8.2, J = 4.7, Н-5'); 8.08
(1Н, d, J = 5.9, Н-7); 8.41 (1Н, ddd, J = 8.2, J = 2.4, J = 1.0, Н-4'); 8.71 (1Н, d, J = 5.9, H-6); 8.84 (1Н, dd,
J = 4.7, J = 1.0, Н-6'); 9.18 (1Н, d, J = 2.4, Н-2'); 9.61 (1Н, s, Н-4). 13С NMR spectrum (DMSO-d6), δ, ppm:
105.8 (С-7); 124.7 (С-5'); 130.5 (С-4'); 132.6 (С-3'); 135.5 (С-7а); 142.9 (С-3а); 143.5 (С-6); 144.2 (С-2');
146.0 (С-6'); 150.1 (С-4). Mass spectrum, m/z (Irel, %): 197 [M]+ (5), 169 [M-N2]+ (43), 168 (13), 142
[169-HCN]+ (11), 129 (4), 118 (3), 115 (15), 103 (5), 88 (6), 78 (37), 64 (28), 52 (25), 51 (100), 50 (72), 38
(37). Found, %: С 60.99; Н 3.69; N 35.30. C10H7N5. Calculated, %: С 60.91; Н 3.58; N 35.51.
1-(2-Pyridyl)-1H-1,2,3-triazolo[4,5-c]pyridine (11c). Yield 0.94 g (95%). Yellowish crystals, mp 196-
197°С (Н2О) (mp 194°С (Н2О) [3]). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.60 (1Н, dd, J = 7.8, J = 5.5,
Н-5'); 8.20 (1Н, dd, J = 8.1, J = 7.8, Н-4'); 8.29 (1Н, d, J = 8.1, Н-3'); 8.49 (1Н, d, J = 5.5, H-6'); 8.73 (2Н, d,
J = 5.0, Н-6,7); 9.63 (1Н, s, Н-4). 13С NMR spectrum (DMSO-d6), δ, ppm: 108.8 (С-7); 114.3 (С-3'); 123.6
(С-5'); 134.4 (С-7а); 140.0 (С-4'); 143.1 (С-3а); 144.1 (С-6); 146.4 (С-6'); 148.8 (С-4); 150.1 (С-2'). Mass
spectrum, m/z (Irel, %): 197 [M]+ (9), 169 [M-N2]+ (63), 168 (16), 142 [169-HCN]+ (12), 118 (4), 115 (6),
1247

91 (4), 78 (100), 64 (36), 52 (47), 51 (94), 50 (56), 38 (38). Found, %: С 60.90; Н 3.73; N 35.48. C10H7N5.
Calculated, %: С 60.91; Н 3.58; N 35.51.
3-(4-Pyridyl)-3H-1,2,3-triazolo[4,5-b]pyridine (18). Yield 0.91 g (92%). Light-gray crystals, mp
1
197-198°С (Н2О) (mp 196-198°С [26], mp 195-197°С [24]). Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
7.67 (1Н, dd, J = 8.2, J = 4.6, Н-6); 8.41 (2Н, d, J = 5.5, Н-3',5'); 8.75 (1Н, d, J = 8.2, Н-7); 8.86 (2Н, d,
J = 5.5, Н-2',6'); 8.91 (1Н, d, J = 4.6, H-5). 13С NMR spectrum (DMSO-d6), δ, ppm: 114.0 (С-3',5'); 121.3
(С-6); 129.6 (С-7); 137.7 (С-7а); 142.4 (С-4'); 144.9 (С-3а); 151.4 (С-2',6'); 151.8 (С-5). Mass spectrum, m/z
(Irel, %): 197 [M]+ (4), 169 [M-N2]+ (26), 142 [M-N2-HCN]+ (4), 127 (4), 92 (18), 78 (45), 64 (17), 52 (11), 51
(100), 50 (33), 38 (20). Found, %: С 60.95; Н 3.70; N 35.33. C10H7N5. Calculated, %: С 60.91; Н 3.58; N 35.51.
Aza-γ-carbolines 16a-d (General Method). A. A suspension of triazolopyridine 11a-c or 18 (0.20 g,
1.0 mmol) in PPA (1.20 g) was heated with stirring to 310°C and maintained for 5 min at 310-320°C. After
cooling, the reaction mixture was dissolved in a small volume of water, made basic by adding ammonium
hydroxide, and cooled. The precipitate formed was filtered off. If a precipitate did not form, the solution was
evaporated to dryness and the residue was washed several times with hot ethanol. Then ethanol was evaporated
off, and water (1 ml) was added to the dry residue. The residue was filtered off, washed on the filter with a small
amount of ice water, and dried in a desiccator over solid sodium hydroxide. When a mixture of products was
formed, the individual products were separated by chromatography on silica gel. The eluents are indicated below.
B. By analogy with method A, but the reaction mixture was heated at 220-230°C for 10 min until gas
evolution ceased.
C. A suspension of triazolopyridine 11a-c or 18 (0.20 g, 1.0 mmol) in PPA (1.2 g) was heated in a heat-
resistant glass flask for 3 min in a 170 W household microwave oven. The reaction mixture was treated by
analogy to the method A.
5H-Pyrido[3',4':4,5]pyrrolo[3,2-c]pyridine (3,6-diazacarbazole, 8-aza-γ-carboline) (16a) was
obtained from the triazolopyridine 11a. The product obtained by methods A and B did not require
chromatographic purification. In the case of method C, 15:1 EtOAc–MeOH was used as the eluent for column
chromatography. Yield 0.098 g (58%, method A), 0.117 g (69%, method B), 0.051 g (30%, method C). Light
gray crystals, mp 315-316°C (H2O) (mp > 300°C [28], mp 344-347°C [10], mp 328°C [13], 312-313°C (subl.)
[29]). The 1H and 13C NMR spectra were identical to the spectra presented in our previous work [29].
When the reaction was carried out by using the method C, 3-hydroxy-4-(4-pyridylamino)pyridine
(17a) was also formed as gray crystals. The eluent was 4:1 EtOAc–MeOH. Yield 0.082 g (44%); mp 194-195°С
1
(EtOH–H2O) (mp 258-260 °C [10]). Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.13 (2Н, d, J = 5.7,
Н-3',5'); 7.28 (1Н, d, J = 5.3, Н-5); 7.97 (1Н, d, J = 5.3, Н-6); 8.16 (1Н, s, Н-2); 8.30 (2Н, d, J = 5.7, Н-2',6');
8.65 (1Н, br. s, NH). 13С NMR spectrum (DMSO-d6), δ, ppm: 111.3 (С-3',5'); 113.1 (С-5); 135.1 (C-3); 136.8
(С-2); 140.6 (С-6); 145.1 (С-4); 147.8 (С-2',6'); 150.1 (С-4'). Mass spectrum, m/z (Irel, %): 187 [M]+ (100), 186
(13), 170 [M-OH]+ (9), 169 (25), 131 (9), 121 (10), 79 (16), 78 (10), 67 (7), 52 (31), 51 (43), 50 (11), 39 (24),
38 (19). Found, %: С 63.95; Н 4.78; N 22.56. C10H9N3О. Calculated, %: С 64.16; Н 4.85; N 22.45.
5H-Pyrido[3',4':4,5]pyrrolo[2,3-c]pyridine (2,6-diazacarbazole, 7-aza-γ-carboline) (16b) was
obtained from triazolopyridine 11b using 15:1 EtOAc–MeOH as the eluent. Yield 0.018 g (11%) by method A,
0.045 g (27%) by method B, and 0.018 g (11%) by method C. Light cream-colored crystals. Mp 236-237°С
(H2O). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz)*: 7.53 (1Н, dd, J = 5.9, J= 0.9, Н-9); 8.13 (1Н, dd, J = 5.1,
J = 0.8, Н-4); 8.39 (1Н, d, J = 5.1, Н-3); 8.48 (1Н, d, J = 5.9, Н-7); 8.93 (1Н, d, J= 0.9, Н-6); 9.38 (1Н, d, J = 0.8,
H-1); 11.33 (1Н, br. s, NH). 13С NMR spectrum (DMSO-d6), δ, ppm: 107.2 (С-4); 115.0 (С-9); 118.1 (C-9a); 122.3
(С-9b); 134.6 (С-6); 137.8 (С-5a); 139.7 (С-8); 140.2 (C-4a); 144.7 (С-3); 146.5 (С-1). Mass spectrum, m/z (Irel, %):
169 [M]+ (100), 168 (27), 143 (9), 142 [M-HCN]+ (8), 141 (8), 115 [M-2HCN]+ (8), 114 (14), 103 (4), 88 (12), 87
(12), 76 (19), 75 (13), 63 (12), 62 (14), 52 (19), 51 (10), 50 (14), 39 (24), 38 (15). Found, %: С 69.09; Н 4.37;
N 24.15. C10H7N3·0.25Н2О. Calculated, %: С 69.15; Н 4.35; N 24.19.
_______
*The numbering of the atoms in 16b-d is given in accord with our previous review [27].
1248

5H-Pyrido[3',4':4,5]pyrrolo[3,2-b]pyridine (3,5-diazacarbazole, 9-aza-γ-carboline) (16d) was
obtained from the triazolopyridine 11b. Eluent 20:1 EtOAc–EtOH. Yield 0.022 g (13%, method A), 0.057 g
1
(34%, method B), 0.017 g (10%, method C). Light-gray crystals, mp 264-265°С (decomp., Н2О). Н NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 7.40 (1Н, dd, J = 8.2, J = 4.6, Н-3); 7.47 (1Н, dd, J = 5.7, J = 0.8, Н-6);
7.89 (1Н, dd, J = 8.2, J = 1.1, Н-4); 8.47 (1Н, d, J = 5.7, Н-7); 8.50 (1Н, dd, J = 4.6, J = 1.1, Н-2); 9.36 (1Н, d,
J = 0.8, H-9); 11.74 (1Н, br. s, NH). 13С NMR spectrum (DMSO-d6), δ, ppm: 107.0 (С-6); 118.4 (C-9a); 118.8
(С-3); 121.0 (С-4); 132.9 (С-4a); 139.9 (С-9b); 142.5 (С-7); 142.6 (С-9); 144.2 (С-5а); 145.6 (С-2). Mass
spectrum, m/z (Irel, %): 169 [M]+ (100), 168 (37), 143 (12), 142 [M-HCN]+ (9), 141 (9), 115 [M-2HCN]+ (7),
114 (11), 103 (4), 88 (8), 87 (8), 76 (20), 62 (13), 52 (20), 51 (12), 50 (17), 39 (35), 38 (20). Found, %: С 68.63;
Н 4.35; N 23.88. C10H7N3·0.33Н2О. Calculated, %: С 68.56; Н 4.41; N 23.99.
Changing the eluent to 1:1 EtOAc–MeOH permitted the isolation of 3-hydroxy-4-(3-pyridyl-
amino)pyridine (17b). Yield 0.097 g (52%, method A), 0.065 g (35%, method B), 0.097 g (52%, method C).
1
Dark-violet crystals, mp 103-104°С. Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.02 (1Н, d, J = 5.5, Н-5);
7.34 (1Н, dd, J = 8.2, J= 4.7, Н-5'); 7.67 (1Н, dd, J = 8.4, J = 2.4, Н-4'); 7.82 (1Н, d, J = 5.5, Н-6); 7.99 (1Н, s,
Н-2); 8.22 (1Н, d, J = 5.5, H-6'); 8.32 (1Н, br. s, NH); 8.34 (1Н, br. s, OH); 8.53 (1Н, d, J = 2.4, Н-2').
13С NMR spectrum (DMSO-d6), δ, ppm: 106.9 (С-5); 123.8 (С-4'); 127.2 (С-5'); 133.2 (С-2'); 134.0 (С-4);
137.1 (С-3); 139.5 (С-6'); 142.7 (С-2); 143.2 (С-3'); 143.4 (С-6). Mass spectrum, m/z (Irel, %): 187 [M]+ (100),
186 (69), 170 [M-OH]+ (24), 158 (54), 142 (10), 134 (16), 131 (42), 121 (10), 105 (10), 104 (19), 94 (15), 83
(16), 79 (45), 78 (43), 67 (49), 64 (24), 55 (44), 52 (76), 51 (96), 50 (40), 39 (100), 38 (74). Found, %: С 64.02;
Н 4.98; N 22.36. C10H9N3О. Calculated, %: С 64.16; Н 4.85; N 22.45.
9H-Pyrido[3',4':4,5]pyrrolo[2,3-b]pyridine (1,6-diazacarbazole, 6-aza-γ-carboline) (16c) was
obtained from triazolopyridine 11c. Eluent 20:1 EtOAc–EtOH. Yield 0.041 g (24%, method A), 0.074 g (44%,
method B), 0.056 g (33%, method C). Light cream-colored crystals, mp 245-246°С (decomp.) (MeOH–EtOAc)
(mp > 237°C (decomp.) [30]). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.32 (1Н, dd, J = 7.6, J = 4.6,
Н-3); 7.49 (1Н, dd, J = 5.7, J= 0.8, Н-8); 8.49 (1Н, d, J = 5.7, Н-7); 8.50 (1Н, dd, J = 4.6, J = 1.6, Н-2); 8.63 (1Н,
dd, J = 7.6, J= 1.6, Н-4); 9.38 (1Н, d, J = 0.8, H-9); 12.26 (1Н, br. s, NH). 13С NMR spectrum (DMSO-d6), δ, ppm:
106.6 (С-8); 113.5 (C-4a); 116.4 (С-3); 117.5 (С-4b); 129.2 (С-4); 143.0 (С-9a); 143.6 (С-7); 145.4 (С-5); 147.2
(С-8а); 151.8 (С-2). Mass spectrum, m/z (Irel, %): 169 [M]+ (100), 168 (12), 142 [M HCN]+ (10), 141 (10), 128 (12),
115 [M-2HCN]+ (10), 114 (22), 103 (10), 88 (23), 87 (28), 76 (21), 75 (23), 63 (33), 62 (33), 52 (29), 51 (21), 50
(23), 39 (28), 38 (24). Found, %: С 71.25; Н 4.20; N 24.95. C10H7N3. Calculated, %: С 70.99; Н 4.17; N 24.84.
Changing the eluent to 5:1 EtOAc–MeOH permitted the isolation of 3-hydroxy-4-(2-pyridyl-
1
amino)pyridine (17c). Yield 0.088 g (47%, method B). Light-brown crystals, mp 87-88°С. Н NMR spectrum
(DMSO-d6), δ, ppm (J, Hz): 6.90 (1Н, ddd, J = 7.2, J= 5.1, J= 0.6, Н-5'); 7.27 (1Н, dd, J = 8.4, J= 0.6, Н-3');
7.67 (1Н, ddd, J = 8.4, J= 7.2, J = 1.8, Н-4'); 7.90 (1Н, d, J = 5.4, Н-5); 8.01 (1Н, s, Н-2); 8.24-8.26 (2Н, m,
13
Н-6,6'); 8.82 (1Н, br. s, NH). С NMR spectrum (DMSO-d6), δ, ppm: 111.3 (С-5); 112.8 (С-3'); 115.7 (С-5');
133.5 (С-2); 137.7 (С-4'); 138.1 (С-6); 138.2 (С-3); 143.8 (С-4); 146.4 (С-6'); 154.6 (С-2'). Mass spectrum, m/z
(Irel, %): 187 [M]+ (20), 186 (6), 170 [M-OH]+ (100), 131 (14), 128 (12), 105 (7), 79 (45), 78 (56), 76 (22), 75
(23), 67 (23), 66 (15), 52 (72), 51 (43), 50 (16), 39 (37), 38 (30). Found, %: С 64.35; Н 4.70; N 22.30.
C10H9N3О. Calculated, %: С 64.16; Н 4.85; N 22.45.
3-Hydroxy-2-(4-pyridylamino)pyridine (21) was obtained from triazolopyridine 18. Chromatographic
purification was not required. Yield 0.105 g (56%, method A), 0.135 g (72%, method B), 0.142 g (76%, method
C). Light-gray crystals, mp 258-259°С (decomp.) (EtOH–H2O). 1Н NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
6.79 (1Н, dd, J= 7.8, J= 4.8, Н-5); 7.12 (1Н, dd, J = 7.8, J= 1.2, Н-4); 7.76 (1Н, dd, J = 4.8, J= 1.2, Н-6); 7.86
(2Н, d, J = 5.5, Н-3',5'); 8.27 (2Н, d, J = 5.5, H-2',6'); 8.63 (1Н, br. s, NH); 10.42 (1Н, br. s, ОН). 13С NMR
spectrum (DMSO-d6), δ, ppm: 112.0 (С-3',5'); 116.8 (С-5); 120.2 (С-4); 136.8 (С-6); 141.4 (С-3); 144.6 (С-4');
148.3 (С-2); 149.0 (С-2',6'). Mass spectrum, m/z (Irel, %): 187 [M]+ (85), 186 (100), 170 [M-OH]+ (15), 132 (19),
105 (8), 94 (11), 79 (12), 78 [Py]+ (16), 67 (16), 55 (45), 54 (23), 51 (49), 50 (15), 39 (56), 38 (14), 36 (13). Found,
%: С 64.02; Н 4.98; N 22.36. C10H9N3О. Calculated, %: С 64.16; Н 4.85; N 22.45.
1249

REFERENCES
1.
2.
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