An efficient route to polynitrogen-fused tricycles via a nitrene-mediated N-N bond formation under microwave irradiation

Article abstract of DOI:10.1016/j.tet.2008.07.055

The synthesis of unprecedented fused azaheterocyclic ring systems is described. Tricycles with either a central pyrazole or a triazole ring were obtained via a nitrene-mediated reaction of nitro bis(hetaryl) derivatives in the presence of triethylphosphite. The cyclization proceeded with complete chemoselectivity for the desired N-N bond formation and was completed within minutes under microwave activation. The key nitro bicycles were synthesized using either Stille couplings or aromatic nucleophilic substitution.

Full text of DOI:10.1016/j.tet.2008.07.055

Tetrahedron 64 (2008) 9567–9573
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient route to polynitrogen-fused tricycles via a nitrene-mediated
N–N bond formation under microwave irradiation
,
Coralie Nyffenegger a b, Eric Pasquinet a, Franck Suzenet b, Didier Poullain a, Christian Jarryc,
c
b,
*
´
´
Jean-Michel Leger , Gerald Guillaumet
a
`
Commissariat a l’Energie Atomique, Le Ripault, BP 16, 37260 Monts, France
b Institut de Chimie Organique et Analytique, Universite´ d’Orle´ans, UMR CNRS 6005, LRC CEA M09, BP 6759, Rue de Chartres, 45067 Orle´ans Cedex 2, France
c EA 4138 Pharmacochimie, Universite´ de Bordeaux 2, 146 rue Le´o Saignat, 33076 Bordeaux Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 June 2008
Received in revised form 15 July 2008
Accepted 15 July 2008
Available online 19 July 2008
The synthesis of unprecedented fused azaheterocyclic ring systems is described. Tricycles with either
a central pyrazole or a triazole ring were obtained via a nitrene-mediated reaction of nitro bis(hetaryl)
derivatives in the presence of triethylphosphite. The cyclization proceeded with complete chemo-
selectivity for the desired N–N bond formation and was completed within minutes under microwave
activation. The key nitro bicycles were synthesized using either Stille couplings or aromatic nucleophilic
substitution.
Keywords:
Cyclization
Ó 2008 Published by Elsevier Ltd.
Nitrene
Nitrogen heterocycles
Stille reaction
1. Introduction
competitive pathways (e.g., C–N cyclization, H-abstraction,
dimerization, C–H insertion).11
Fused polyheterocycles have been the subject of numerous
studies due to their pharmacological1 and energetic properties.2
Such compounds have mainly been prepared by amination–cycli-
zation of heteroaryl derivatives containing a carbonyl or a halogen,3
by cyclization of o-amino/o-heteroacetylenes,4 or by reductive
cyclization on a nitrohetaryl.5
Previous work from our laboratory has consisted in the syn-
thesis of nitrogen-rich tricycles with a pyrimidin-4-one as the
central core.6 The key reaction was an N-heteroarylation under
Pd-catalyzed conditions, developed in a preliminary study.7
In a further step toward a general route to other related fused
azaheterocyclic compounds, the present communication describes
the synthesis of tricycles with either a pyrazole or a 1,2,3-triazole as
the central ring. The underlying strategy was based on the creation
of the desired central ring via an intramolecular, nitrene-mediated
N–N bond formation from a bis(hetaryl) precursor. Such a strategy
pioneered by Cadogan8 and Abramovitch9 has been widely used on
phenyl hetaryls.10 Depending on the substrates and conditions, C–N
or N–N cyclization has been observed. As a general trend, singlet
nitrenes favor N–N cyclization, while triplet nitrenes favor
Though a number of heterocyclic nitrenes have been in-
vestigated,12 the literature is very scarce concerning the nitrene-
mediated cyclization of a bis(hetaryl) systems. In a few cases, the
final product was a fused tetracycle.13 The present article dem-
onstrates that bicyclic nitro precursors can be used to generate
bicyclic hetaryl nitrenes. Such a reaction was shown to be very
efficient under microwave irradiations and was found to occur
with complete chemoselectivity for N–N cyclization to give a
variety of new fused azaheterocyclic tricycles [Scheme 1,
Ar1¼(substituted) pyrazolyl, pyridyl, or pyrimidinyl, Ar2¼(substi-
tuted) pyridyl].
Though several other methods have been recently described,14
the most common precursors of nitrenes are azido or nitro de-
rivatives.10 Thermal or photo-induced decompositions of these
compounds lead to intermediate nitrenoid species, known to cy-
clize intramolecularly with an adjacent aromatic ring. In the case of
nitro precursors, a deoxygenating agent is required. Phosphites and
phosphines have been used,15,8a triethylphosphite being the more
popular reagent.
Since nitro compounds are more readily available than their
azido counterparts, the present strategy was based on cyclization
from a nitro bicycle. It was first envisioned that a pallado-catalyzed
carbon–carbon cross-coupling would be a useful method for
building the desired nitro-functionalized bis(heterocyclic)
* Corresponding author.
E-mail address: gerald.guillaumet@univ-orleans.fr (G. Guillaumet).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.07.055

9568
C. Nyffenegger et al. / Tetrahedron 64 (2008) 9567–9573
N
N
N
N-N cyclization
N
N
C-N cyclization
Ar1
N
Ar2
Ar1
Ar2
Ar2
Ar1
Scheme 1. Cyclization of arylnitrenes: N–N versus C–N pathway.
Table 1
skeleton. Upon cyclization, tricycles with a central pyrazole ring
should be produced.
Synthesis of nitro bishetaryls 1a–1g and microwaves promoted cyclization to
products 2a–2g
R2
R1
R1
2. Results and discussion
R2
N
NO2
O2N
Cl
Y
PdCl2(Ph3)2,CuI
DMF, 115°C
The Stille coupling between 2-tributylstannylpyridine and
2-chloro-3-nitropyridine was thus examined for the synthesis of
bicycle 1a as a model reaction (Table 1, R1¼R2¼R3¼H, X¼Z¼N,
Y¼CH). Pd(PPh3)2Cl2 was used as the catalyst and the addition of
CuI turned out to significatively improve the yields. The best re-
sults were obtained in DMF at 115 ꢀC yielding 68% of pure isolated
1a. Similarly, other nitro bicycles, i.e., 1b–1g, were synthesized in
fair yields (Table 1). The generality of the Stille coupling was
demonstrated by the use of various substituted tributyl-
stannylpyridines, a tributylstannylpyrimidine as well as a variety of
chloronitropyridine derivatives. The degradation and, in some
cases, a homocoupling (ca. 10%) of the tributylstannyl derivative
were observed.
Z
Z
N
+
R3
X
X
Y
SnBu3
R3
R1 = H, Me, CN
R2 = H, OMe
Z = CH or N
1a-1g
X = CH and Y = N
or X = N and Y = CH
R
3 = H, OMe
R2
Z
R1
N
N
(EtO)3P, 176°C
MW
Y
X
R3
2a-2g
The cyclization conditions in the presence of triethylphosphite
as a deoxygenative agent were then studied using 3-nitro-2-
(pyrimidin-2-yl)pyridine 1a. From this bicycle, the cyclization
could only proceed through the formation of an N–N bond. Though
classical heating proved efficient, microwave activation was pre-
ferred since reaction times could be substantially decreased
with this method. At 176 ꢀC, with an irradiating power of 300 W,
the expected tricycle 2a was obtained within 12 min in an 86%
isolated yield (Table 1, entry 1). The versatility of the cyclization
could be demonstrated by using different bicyclic nitro precursors
(Table 1).
It is noteworthy that the various 3-nitro-2-(pyrid-2-yl)pyridines
1b–1g cyclized with complete chemoselectivity, affording exclu-
sively the desired tricycles from an N–N bond formation despite an
available C–N cyclization site (Table 1). Moreover, the usual side
products (i.e., amino, azo, azepine derivatives) were not observed.
Yields were high regardless of the nature and position of the
substituents on the bis(hetaryl) derivatives. It could, however, be
noticed that longer reaction times were required for compounds 1e
and 1f to go to completion (Table 1, entries 5–6). This corroborated
the observation of Suschitzky and co-workers11 for 1-(2-nitro-
Entry
Nitro precursors, yield
Cyclization
Tricycle, yield
time (min)
12
N
N
N
NO2
N
N
1
N
N
2a, 86%
1a, 68%
O2N
N
2
3
4
5
24
24
24
36
N
N
N
N
2b, 81%
1b, 75%
O2N
N
N
N
N
2c, 84%
N
N
1c, 59%
O2N
N
N
N
N
MeO
phenyl)pyrazoles. As
a matter of fact, the electron-donating
MeO
NC
2d, 87%
methoxy group could affect the reactivity of the intermediate
electrophilic nitrenoid species derived from 1f. In the case of 1e, the
electron-withdrawing cyano group could decrease the electron
density of the pyridine ring and therefore lower the reactivity of the
lone pair of the nitrogen atom of the pyridine. In view of this result,
it was surprising that one of the shortest cyclization times was
recorded for compound 1a in spite of the more electron-deficient
character of the pyrimidine ring (Table 2, entry 1). The cyclization
also proceeded cleanly for 1g, thus giving a tricycle with a pyri-
do[3,4-c]pyrazole moiety (Table 1, entry 7).
Compounds 2a–2g represent, to the best of our knowledge,
the first examples of three unprecedented ring systems, namely
pyrazolo[1,5-a:4,3-b0]dipyridine, pyrazolo[1,5-a:3,4-c0]dipyridine,
and pyrido[30,20:3,4]pyrazolo[1,5-a]pyrimidine. Crystals of 2a were
grown and its structure was confirmed by X-ray analysis (Fig. 1).
By examining these results, it was anticipated that the strategy
could be further extended to access new azaheterocyclic fused
compounds with a central betainic 1,2,3-triazole ring. The aromatic
nucleophilic substitution of halogenopyridines by pyrazoles in the
presence of bases has been well documented.16 A variety of bases
1d, 79%
O2N
N
NC
N
N
2e, 87%
N
N
1e, 47%
O2N
OMe
N
6
7
36
12
N
N
N
N
OMe
N
2f, 79%
1f, 60%
O2N
N
N
N
2g, 71%
N
1g, 71%
and solvents were thus screened for the reaction between 2-chloro-
3-nitropyridine and pyrazole. Cesium carbonate in acetonitrile was
the most efficient combination and gave rise to bicycle 3a with

C. Nyffenegger et al. / Tetrahedron 64 (2008) 9567–9573
9569
Table 2
Synthesis of nitro bishetaryls 3a–3e and microwaves promoted cyclization to
products 4a–4g
R2
N
R1
H
N
NO2
Cl
R3
X
N
Y
Cs2CO3
N
+
R3
X
R1
MeCN, reflux
Y
R2
NO2
R3 = H, OMe
3a-3e
R
R
1 = H, Me
2 = H, Me, CF3
X = CH and Y = N
or X = N and Y = CH
Figure 2. ORTEP view of 4c.
R2
R3
X
As for the synthesis of tricycles 2a–2g, the cyclization leading to
4a–4e was performed using triethylphosphite under microwave
irradiation. Again, also for this series, only the tricyclic compounds
arising from an N–N bond formation between the pyrazole nitrogen
and the electrophilic nitrene were isolated. Clean reactions and
high yields were observed for compounds 4a–4c despite the
presence of electron-withdrawing functional groups on the pyr-
azole core (Table 2, entry 3). Moreover, it should be noted that in
the case of 3-nitro-2-(3,5-dimethylpyrazol-1-yl)pyridine 3b, the
insertion product of the nitrene in a methyl C–H was not observed,
though this could have been possible.11a
Nevertheless, a modification of the nitropyridine moiety sub-
stantially affected the cyclization. Thus the cyclization of 3e (the
only 4-(pyrazol-1-yl)pyridine) was sluggish and the tricycle 4e was
isolated at a yield of only 20% (Table 2, entry 5). Degradation was
observed to a large extent even though the temperature was low-
ered to 105 ꢀC. The introduction of an electron-donating group on
the pyridine ring also proved to be detrimental to the reaction. In
the case of 3d, the expected cyclization did not occur. All that was
noticed was the corresponding phosphoramidate 5 and degrada-
tion products (Table 2, entry 4). The formation of phosphor-
amidates in this type of reaction has been reported,17 and they were
found not to be the intermediates of the cyclized product.
R1
N
(EtO)3P, 176 °C
MW
N
Y
N
4a-4e
Entry
1
Bicyclic precursor, yield
Cyclization product, yield
N
N
N
N
N
N
N
NO2
3a, 92%
4a, 85%
N
N
N
N
N
N
2
3
NO2
N
3b, 54%
4b, 92%
CF3
N
N
N
N
N
CF3
N
N
NO2
4c, 82%
3c, 92%
Crystals suitable for X-ray analysis were obtained in the case of
4c, and the betaine structure of the central 1,2,3-triazole ring could
thus be confirmed. The recorded N–N and C–N bond lengths on the
1,2,3-triazole moiety were similar to the ones determined for the
very few related structures resolved by X-ray18 (Fig. 2).
N
N
N
MeO
MeO
N
N
N
4
5
NH
EtO
P
O
NO2
3d, 67%
EtO
5, 35%
N
3. Conclusion
N
N
N
N
N
N
In summary, the deoxygenation–cyclization of nitro bis(hetaryl)
derivatives led to new polynitrogen-fused tricyclic compounds via
a nitrenoid pathway. The reaction proceeded with complete che-
moselectivity to exclusively afford products arising from an N–N
bond formation. This resulted in the synthesis of derivatives of five
new ring systems: pyrazolo[1,5-a:4,3-b0]dipyridine, pyrazolo[1,5-
NO2
3e, 84%
4e, 20%
a:3,4-c0]dipyridine,
pyrido[30,20:3,4]pyrazolo[1,5-a]pyrimidine,
pyrazolo[10,20:2,3][1,2,3]triazolo[4,5-b]pyridine, and pyrazolo[10,20:
1,2][1,2,3]triazolo[4,5-c]pyridine.
4. Experimental
4.1. General
1H and 13C NMR chemical shifts were calibrated according to
CDCl3 signal (1H: 7.27 ppm; 13C: 77.23 ppm), and the 15N NMR
chemical shifts according to an external reference CH3NO2 (0 ppm)
using a Bruker Avance 200 and Avance 400 WB spectrometers.
Multiplicity is indicated using the following abbreviations: s for
a singlet, d for a doublet, t for a triplet, q for a quadruplet. For
carbon: C, CH, CH2, CH3 were determined according to DEPT anal-
yses. Infrared spectra were recorded with an attenuated total
Figure 1. ORTEP view of 2a.
a yield of 92%. These conditions allowed access to a new variety of
other nitrobis(hetaryl) derivatives (Table 2). The yields ranged from
54 to 92%.

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C. Nyffenegger et al. / Tetrahedron 64 (2008) 9567–9573
reflectance Perkin–Elmer SpectrumOne spectrometer. Melting
points were determined on a Differential Scanning Calorimetry
Q100, TA Instruments. Elemental analyses were performed on
a ThermoFisher Scientific Flash EA1112 CHNS/O apparatus. Mass
spectra were recorded on a Varian MS 1200 Quadrupole spec-
trometer using chemical ionization. High resolution mass spectra
(HRMS) were obtained using chemical ionization (CI) and recorded
(CDCl3)
d
3.84 (s, 3H), 6.79 (d, J¼1.0 and 8.0 Hz, 1H), 7.39 (dd, J¼4.7
and 8.1 Hz, 1H), 7.71 (t, J¼7.4 and 8.0 Hz, 1H), 7.81 (dd, J¼1.0 and
7.4 Hz, 1H), 7.91 (dd, J¼1.5 and 8.1 Hz, 1H), 8.74 (dd, J¼1.5 and
4.7 Hz, 1H); 13C NMR (CDCl3)
d 53.7 (CH3), 112.7 (CH), 115.9 (CH),
123.4 (CH), 131.8 (CH), 139.5 (CH), 146.7 (C), 149.2 (C), 150.6 (C),
150.9 (CH), 163.2 (C); MS (CIþ) m/z 260 (MþC2H5þ), 232 (MHþ), 202
(MHþꢁNO). Anal. Calcd for C11H9N3O3: C 57.14%; H 3.92%; N 18.17%.
Found: C 56.87%; H 4.21%; N 18.42%.
on
a Waters-micromass GCT Premier apparatus. Microwave-
assisted reactions were performed with a CEM Discover apparatus.
Chromatographic purification of products was carried out
using prepacked Analogix Superflash Si50 columns. Solid phase
extraction was performed on Discovery DSC-NH2 cartridges.
4.2.5. 30-Nitro-2,20-bipyridine-5-carbonitrile 1e
The title compound was isolated as a pale yellow solid in a 47%
yield. Mp 179 ꢀC; IR:
n
(cmꢁ1) 3073, 2957, 2923, 2241, 1591, 1526,
1463, 1446, 1363, 1025, 847, 829, 746, 733; 1H NMR (CDCl3)
(dd, J¼4.7 and 8.1 Hz, 1H), 8.12–8.19 (m, 2H), 8.27 (d, J¼8.1 Hz, 1H),
8.86–8.89 (m, 2H); 13C NMR (CDCl3)
110.6 (C), 116.5 (C), 123.3
d 7.59
4.2. Procedure for compounds 1a–1g
d
5-Methyl-2-(tributylstannyl)pyridine and 2-methoxy-6-(tribu-
tylstannyl)pyridine were bought from Synthonix.
(CH), 124.9 (CH), 132.6 (CH), 140.6 (CH), 147.0 (C), 148.8 (C), 151.7
(CH),151.7 (CH),157.2 (C); MS (CIþ) m/z 227 (MHþ),197 (MHþꢁNO);
HRMS (CIꢁ) calcd for C11H6N4O2 (M) 226.0491, found 226.0485.
To a degassed solution of the chloronitropyridine (6 mmol,
1 equiv) and tributylstannyl derivatives (6.6 mmol, 1.1 equiv) in
DMF (33 mL) were added CuI (0.6 mmol, 0.01 equiv) and
PdCl2(PPh3)2 (0.3 mmol, 0.01 equiv) under an inert atmosphere.
After stirring for 18 h at 115 ꢀC, 1 N aqueous KF (9 mL) was added,
and the resulting mixture was stirred for 30 min, and then passed
through a short Celite pad. The Celite was washed with Et2O, the
filtrate was concentrated, and purified by column chromatography
(elution with heptane/AcOEt) to give the expected bicycle as a solid.
If traces of DMF remained, further purification using an SPE car-
tridge (elution with dichloromethane) allowed to get the pure solid.
4.2.6. 6-Methoxy-3-nitro-2,20-bipyridine 1f
The title compound was isolated as a yellow solid in a 60% yield.
Mp 111 ꢀC; IR:
n
(cmꢁ1) 2957, 1581, 1522, 1471, 1415, 1359, 1327,
1260, 1122, 1097, 1013, 799, 762; 1H NMR (CDCl3)
d 4.05 (s, 3H), 6.83
(d, J¼8.8 Hz,1H), 7.34 (ddd, J¼1.4, 4.9, and 7.5 Hz,1H), 7.85 (td, J¼1.8
and 7.5 Hz, 1H), 7.95 (d, J¼7.5 Hz, 1H), 8.04 (d, J¼8.8 Hz, 1H), 8.59 (d,
J¼4.7 Hz, 1H); 13C NMR (CDCl3)
d 54.7 (CH3), 110.9 (CH), 123.2 (CH),
124.4 (CH), 135.6 (CH), 137.0 (CH), 141.0 (C), 149.1 (CH), 150.1 (C),
154.5 (C), 164.2 (C); MS (CIþ) m/z 260 (MþC2H5þ), 232 (MHþ), 202
(MHþꢁNO); HRMS (CIþ) calcd for C11H9N3O3 (MHþ) 232.0722,
found 232.0721.
4.2.1. 2-(3-Nitropyridin-2-yl)pyrimidine 1a
The title compound was isolated as a white solid in a 68% yield.
Mp 102 ꢀC; IR:
n
(cmꢁ1) 3070, 1599, 1558, 1525, 1471, 1406, 1356,
4.2.7. 30-Nitro-2,40-bipyridine 1g
1058, 860, 824, 759; 1H NMR (CDCl3)
d
7.34 (t, J¼4.9 Hz, 1H), 7.54
The title compound was isolated as an orange solid in a 71%
(dd, J¼4.8 and 8.2 Hz, 1H), 8.17 (dd, J¼1.5 and 8.2 Hz, 1H), 8.83 (d,
yield. Mp 131–132 ꢀC; IR: (cmꢁ1) 3045, 1603, 1585, 1525, 1462,
n
J¼4.9 Hz, 2H), 8.88 (dd, J¼1.5 and 4.8 Hz, 1H); 13C NMR (CDCl3)
1434, 1369, 1187, 992, 864, 854, 796, 756, 697; 1H NMR (CDCl3)
d
120.9 (CH), 124.6 (CH), 132.3 (CH), 146.7 (C), 149.6 (C), 152.3 (CH),
d
7.37 (ddd, J¼0.94, 4.9, and 7.7 Hz, 1H), 7.53 (d, J¼7.8 Hz, 1H), 7.58
157.6 (2CH), 162.3 (C); MS (CIþ) m/z 203 (MHþ), 173 (MHþꢁNO);
(d, J¼5.0 Hz, 1H), 7.83 (td, J¼1.7 and 7.8 Hz, 1H), 8.65 (dd, J¼0.9 and
HRMS (CIþ) calcd for C9H6N4O2 (MHþ) 202.0569, found 203.0567.
4.9 Hz, 1H), 8.85 (d, J¼5.0 Hz, 1H), 9.07 (s, 1H); 13C NMR (CDCl3)
d
122.8 (CH), 124.3 (CH), 124.8 (CH), 137.3 (CH), 142.3 (C), 145.4 (CH),
4.2.2. 3-Nitro-2,20-bipyridine 1b
145.5 (C), 150.2 (CH), 152.7 (C), 153.2 (CH); MS (CIþ) m/z 202 (MHþ),
171 (MHþꢁNO); HRMS (CIþ) calcd for C10H7N3O2 (MHþ) 202.0617,
found 202.0616.
The title compound was isolated as a white solid in a 75% yield.
Mp 135 ꢀC; IR:
n
(cmꢁ1) 3063, 2958, 2928, 1597, 1585, 1533, 1445,
1420, 1371, 860, 818, 753; 1H NMR (CDCl3)
d
7.29 (ddd, J¼1.6, 4.9,
and 7.7 Hz, 1H), 7.51 (dd, J¼4.8 and 8.1 Hz, 1H), 7.90 (td, J¼1.7 and
7.7 Hz, 1H), 8.07–8.12 (m, 2H), 8.62 (dd, J¼1.6 and 4.8 Hz, 1H), 8.85
4.3. Procedure for compounds 3a–3e
(dd, J¼1.5 and 4.8 Hz,1H); 13C NMR (CDCl3)
d
123.0 (CH),123.4 (CH),
A suspension of the pyrazolyl compound (4.2 mmol, 1.5 equiv)
and Cs2CO3 (4.4 mmol, 1.1 equiv) in anhydrous MeCN (16 mL) was
stirred for 20 min under an inert atmosphere. The solid chloroni-
tropyridine derivative (4 mmol, 1 equiv) was then added. After
stirring under reflux for 18 h, the resulting mixture was filtered and
then diluted in H2O/AcOEt (1:1, 80 mL). The aqueous phase was
extracted with AcOEt (2ꢂ15 mL). The organic layers were washed
with H2O (2ꢂ15 mL), dried over MgSO4, filtered, and concentrated.
The organic residue was purified by column chromatography
(elution with heptane/AcOEt) to give the expected bicycle as a solid.
124.4 (CH), 132.1 (CH), 137.0 (CH), 146.6 (C), 149.0 (CH), 150.5 (C),
151.2 (CH), 153.8 (C); MS (CIþ) m/z 202 (MHþ), 171 (MHþꢁNO);
HRMS (CIþ) calcd for C10H7N3O2 (MHþ) 202.0617, found 202.0616.
4.2.3. 50-Methyl-3-nitro-2,20-bipyridine 1c
The title compound was isolated as a white solid in a 59% yield.
Mp 143 ꢀC; IR:
n
(cmꢁ1) 3048, 1555, 1526, 1448, 1363, 1029, 859,
848, 819, 779, 743, 659; 1H NMR (CDCl3)
d 2.36 (s, 3H), 7.42 (dd,
J¼4.8 and 8.1 Hz, 1H), 7.65 (dd, J¼2.1 and 8.2 Hz, 1H), 7.95–8.03 (m,
2H), 8.41 (d, J¼2.1 Hz, 1H), 8.77 (dd, J¼1.5 and 4.8 Hz, 1H); 13C NMR
(CDCl3)
d
18.5 (CH3), 122.7 (CH), 123.3 (CH), 132.1 (CH), 134.6 (C),
4.3.1. 3-Nitro-2-(1H-pyrazol-1-yl)pyridine 3a
137.6 (CH), 146.6 (C), 149.7 (CH), 150.6 (C), 151.2 (CH), one carbon
signal was not observed; MS (CIþ) m/z 244 (MþC2H5þ), 216 (MHþ),
186 (MHþꢁNO); HRMS (CIþ) calcd for C11H9N3O2 (MHþ) 216.0773,
found 216.0767.
The title compound was isolated as a white solid in a 92% yield.
Mp 95 ꢀC; IR: (cmꢁ1) 3153, 1596, 1527, 1539, 1472, 1395, 1363, 938,
n
856, 757; 1H NMR (CDCl3)
d
6.49 (dd, J¼2.6 and 1.7 Hz,1H), 7.73 (dd,
J¼4.8 and 8.0 Hz, 1H), 7.73 (d, J¼1.4 Hz, 1H), 8.01 (dd, J¼1.6 and
8.0 Hz, 1H), 8.39(d, J¼2.8 Hz, 2H), 8.57 (dd, J¼1.6 and 4.8 Hz, 1H);
4.2.4. 60-Methoxy-3-nitro-2,20-bipyridine 1d
13C NMR (CDCl3)
d 108.7 (CH), 121.9 (CH), 128.9 (CH), 133.7 (CH),
The title compound was isolated as a white solid in a 79% yield.
138.6 (C), 142.5 (C), 143.6 (CH), 150.5 (CH); MS (CIþ) m/z 219
(MþC2Hþ5 ), 191 (MHþ), 161 (MHþꢁNO); HRMS (CIꢁ) calcd for
C8H6N4O2 (M) 190.0491, found 190.0482.
Mp 92 ꢀC; IR:
n
(cmꢁ1) 3071, 2934, 1595, 1574, 1560, 1528, 1479,
1414, 1373, 1331, 1264, 1065, 1017, 852, 814, 763, 726; 1H NMR

C. Nyffenegger et al. / Tetrahedron 64 (2008) 9567–9573
9571
4.3.2. 2-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-nitropyridine 3b
1H), 8.11(dd, J¼1.3 and 7.0 Hz, 1H), 8.74 (m, 2H), 8.95 (dd, J¼1.6 and
7.0 Hz, 1H); 13C NMR (CDCl3)
112.9 (CH), 124.3 (CH), 124.5 (CH),
The title compound was isolated as a yellow solid in a 54% yield.
d
Mp 108 ꢀC; IR:
n
(cmꢁ1) 3047, 2928, 1580, 1595, 1568, 1533, 1482,
130.2 (C), 134.5 (CH), 143.1 (C), 144.8 (CH), 146.9 (CH), 147.0 (C); 15
N
1453, 1434, 1380, 1355, 813, 794, 761, 721; 1H NMR (CDCl3)
d
2.22 (s,
NMR (CDCl3)
d
ꢁ83.8, ꢁ96.5, ꢁ133.0, ꢁ148.6; MS (CIþ) m/z 199
3H), 2.51(s, 3H), 6.04 (s, 1H), 7.39 (dd, J¼4.8 and 8.0 Hz, 1H), 8.15
(MþC2Hþ5 ), 171 (MHþ); HRMS (CIþ) calcd for C9H6N4 (MHþ)
(dd, J¼1.6 and 8.0 Hz, 1H), 8.63 (dd, J¼1.6 and 4.8 Hz, 1H); 13C NMR
171.0592, found 171.0675.
(CDCl3)
d 12.6 (CH3), 13.7(CH3), 109.2 (CH), 122.1 (CH), 133.9 (CH),
141.2 (C), 141.6 (C), 144.9 (C), 150.7 (CH), 151.8 (C); MS (CIþ) m/z 247
(MþC2Hþ5 ), 219 (MHþ); HRMS (CIþ) calcd for C10H10N4O2 (MHþ)
219.0882, found 219.0881.
4.4.2. Pyrazolo[1,5-a:4,3-b0]dipyridine 2b
Total reaction time: 24 min. The title compound was isolated as
a yellow solid in an 81% yield. Mp 103 ꢀC; IR:
n
(cmꢁ1) 3041, 1545,
1518, 1437, 1390, 1330, 1267, 1208, 1142, 1119, 1010, 852, 795, 756,
722, 671; 1H NMR (CDCl3)
d
7.33 (td, J¼1.5 and 6.9 Hz,1H), 7.47–7.55
4.3.3. 3-Nitro-2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]pyridine 3c
The title compound was isolated as a red solid in a 92% yield. Mp
(m, 2H), 8.19(dd, J¼1.3 and 8.7 Hz, 1H), 8.49 (d, J¼8.6 Hz, 1H), 8.68
68 ꢀC; IR:
n
(cmꢁ1) 3168, 3147, 1541, 1465, 1393, 1368, 1277, 1154,
(dd, J¼1.4 and 4.2 Hz, 1H), 8.81 (d, J¼6.9 Hz, 1H); 13C NMR (CDCl3)
1133, 1113, 1046, 952, 784, 773, 755; 1H NMR (CDCl3)
d 6.75(d,
d
118.0 (CH), 118.6 (CH), 123.3 (CH), 123.4.2 (CH), 123.7 (CH), 128.5
(CH), 132.9 (C), 135.4 (C), 143.0 (C), 144.9 (CH); MS (CIþ) m/z 198
(MþC2Hþ5 ), 170 (MHþ); HRMS (CIþ) calcd for C10H7N3 (MHþ)
170.0718, found 170.0712.
J¼2.7 Hz, 1H), 7.50 (dd, J¼4.8 and 8.0 Hz, 1H), 8.04 (dd, J¼1.5 and
8.0 Hz, 1H), 8.41 (d, J¼2.7 Hz, 1H), 8.64 (dd, J¼1.5 and 4.8 Hz, 1H);
13C NMR (CDCl3)
(CH), 130.8 (CH), 134.3 (CH), 139.1 (C), 141.9 (C), 146.0 (q, J¼38.5 Hz,
C, C–CF3), 150.9 (CH); MS (CIþ) m/z 259 (MHþ), 229 (MHþꢁNO);
HRMS (CIþ) calcd for C9H5F3N4O2 (MHþ) 259.0443, found 259.0441.
d
106.7 (CH), 120.6 (q, J¼267.6 Hz, C, CF3), 123.6
4.4.3. 8-Methylpyrazolo[1,5-a:4,3-b0]dipyridine 2c
Total reaction time: 24 min. The title compound was isolated as
a yellow solid in an 84% yield. Mp 148 ꢀC; IR:
n
(cmꢁ1) 3049, 2914,
4.3.4. 6-Methoxy-3-nitro-2-(1H-pyrazol-1-yl)pyridine 3d
1518, 1417, 1381, 1359, 1325, 1272, 1250, 1036, 799, 765, 723, 671; 1H
NMR (CDCl3)
The title compound was isolated as a yellow pale solid in a 67%
d
2.38 (s, 3H), 7.18 (dd, J¼1.0 and 8.8 Hz, 1H), 7.35 (dd,
yield. Mp 137–138 ꢀC; IR:
n
(cmꢁ1) 3153, 2952, 1581, 1535, 1483,
J¼4.2 and 8.7 Hz, 1H), 8.04 (dd, J¼1.3 and 8.7 Hz, 1H), 8.20 (d,
J¼8.8 Hz, 1H), 8.46 (d, J¼1.0 Hz, 1H), 8.54 (dd, J¼1.3 and 4.2 Hz, 1H);
1468, 1447, 1397, 1361, 1300, 1006, 831, 765; 1H NMR (CDCl3)
d 4.04
(s, 3H), 6.49 (dd, J¼1.7 and 2.7 Hz, 1H), 6.72 (d, J¼8.7 Hz, 1H), 7.73
13C NMR (CDCl3)
d 18.7 (CH3), 117.5 (CH), 123.9 (CH), 123.2 (CH),
(d, J¼1.7 Hz, 1H), 7.98 (d, J¼8.7 Hz, 1H), 8.28 (d, J¼2.7 Hz, 1H); 13C
125.9 (CH), 126.5 (CH), 128.3 (C), 133.0 (C), 133.5 (C), 142.6 (C), 144.4
NMR (CDCl3)
d 54.9 (CH3), 108.5 (CH), 109.0 (CH), 128.9 (CH), 132.8
(CH); MS (CIþ) m/z 212 (MþC2H5þ), 184 (MHþ); HRMS (CIþ) calcd for
(C), 136.9 (CH), 141.9 (C), 143.4 (CH), 163,8 (C); MS (CIþ) m/z 248
(MþC2Hþ5 ), 221 (MHþ), 190 (MHþꢁNO); HRMS (CIþ) calcd for
C9H8N4O3 (MHþ) 221.0675, found 221.0678.
C
11H9N3 (MHþ) 184.0875, found 184.0868.
4.4.4. 7-Methoxypyrazolo[1,5-a:4,3-b0]dipyridine 2d
Total reaction time: 24 min. The title compound was isolated as
4.3.5. 3-Nitro-4-(1H-pyrazol-1-yl)pyridine 3e
a yellow solid in an 87% yield. Mp 112–113 ꢀC; IR:
n
(cmꢁ1) 3386,
The title compound was isolated as a white solid in an 84% yield.
3072, 1637, 1586, 1553, 1526, 1543, 1408, 1328, 1310, 1283, 1119,
Mp 115–116 ꢀC; IR:
n
(cmꢁ1) 3150, 3126, 1598, 1523, 1497, 1393,
1024, 848, 793, 748; 1H NMR (CDCl3)
d
4.20 (s, 3H), 6.58 (dd, J¼1.0
1364, 1338, 1029, 935, 848, 760, 716; 1H NMR (CDCl3)
d 6.59 (dd,
and 7.7 Hz, 1H), 7.36–7.44 (m, 2H), 8.02 (dd, J¼1.0 and 8.6 Hz, 1H),
J¼1.8 and 2.6 Hz, 1H), 7.64 (d, J¼5.4 Hz, 1H), 7.84 (m, 2H), 8.84 (d,
8.15 (dd, J¼1.3 and 8.7 Hz, 1H), 8.57 (dd, J¼1.3 and 4.2 Hz, 1H); 13C
J¼5.4 Hz, 1H), 9.01 (s, 1H); 13C NMR (CDCl3)
d 110.2 (CH), 117.7 (CH),
NMR (CDCl3)
d 57.2 (CH3), 95.1 (CH), 110.2 (CH), 123.6 (CH), 124.0
129.4 (CH), 139.1 (C), 139.4 (C), 144.1 (CH), 146.4 (CH), 153.8 (CH);
MS (CIþ) m/z 190 (MHþ), 160 (MHþꢁNO); HRMS (CIþ) calcd for
C8H6N4O2 (MHþ) 191.0569, found 191.0562.
(CH), 124.8 (CH), 132.8 (C), 136.8 (C), 139.0 (C), 143.1 (C), 144.8 (CH),
150.7 (C); MS (CIþ) m/z 228 (MþC2H5þ), 200 (MHþ); HRMS (CIþ)
calcd for C11H9N3O (MHþ) 200.0824, found 200.0822.
4.4.5. Pyrazolo[1,5-a:4,3-b0]dipyridine-8-carbonitrile 2e
4.4. Procedure for compounds 2a–2g, 4a–4c, 4e, and 5
Total reaction time: 36 min. The title compound was isolated as
a yellow solid in an 87% yield. Mp 288 ꢀC; IR: (cmꢁ1) 3032, 2234,
n
A
suspension of bicycle (1.5 mmol, 1 equiv) in (EtO)3P
1639, 1380, 1336, 1321, 1277, 897, 834,816, 798, 771, 731, 719; 1H
(37.5 mmol, 25 equiv) was subjected to a microwave irradiation
cycle at 300 W (2 min to attain 176 ꢀC and then 10 min at 176 ꢀC
with Pobtained¼1–1.3 bars for a Prequested¼4 bars) unless otherwise
stated. The reaction was monitored by TLC and another cycle was
performed as long as the starting material remained. The resulting
mixture was cooled down and concentrated under vacuum using
a Ku¨gelrohr apparatus, and then purified by column chromatogra-
phy (elution with dichloromethane/MeOH) to give the expected
tricycle as a solid.
NMR (CDCl3)
d
7.61 (m, 2H), 8.29 (dd, J¼1.3 and 8.8 Hz, 1H), 8.61 (d,
J¼8.9 Hz, 1H), 8.79 (dd, J¼1.3 and 4.2 Hz, 1H), 9.18 (s, 1H); 13C NMR
(CDCl3)
d 104.5 (CN), 120.1 (CH), 124.5 (CH), 125.6 (CH), 125.9 (CH),
134.6 (CH), 136.2 (C), 145.3 (C), 145.4 (CH), two carbon signals were
not observed; MS (CIþ) m/z 223 (MþC2H5þ), 195 (MHþ); HRMS (CIꢁ)
calcd for C11H6N4 (M) 194.0592, found 194.0584.
4.4.6. 2-Methoxypyrazolo[1,5-a:4,3-b0]dipyridine 2f
In some cases, a substantial amount of tricycle precipitated on
cooling to room temperature. The pure product was collected by
filtration and further amounts of product were obtained after
treatment of the filtrate as above.
Total reaction time: 36 min. The title compound was isolated as
a yellow solid in a 79% yield. Mp 116 ꢀC; IR:
n
(cmꢁ1) 3000, 2986,
1594, 1557, 1527, 1469, 1435, 1396, 1318, 1288, 1269, 1211, 1013, 821,
731; 1H NMR (CDCl3)
d
4.07 (s, 3H), 7.01 (d, J¼6.2 Hz, 1H), 7.07 (ddd,
J¼2.4, 6.9, and 6.9 Hz, 1H), 7.27(ddd, J¼0.9, 6.9, and 8.7 Hz, 1H), 8.04
4.4.1. Pyrido[30,20:3,4]pyrazolo[1,5-a]pyrimidine 2a
(d, J¼9.2 Hz, 1H), 8.19 (d, J¼8.7 Hz, 1H), 8.64 (d, J¼6.9 Hz, 1H); 13C
Total reaction time: 12 min. The title compound was isolated as
NMR (CDCl3) d 53.70 (CH3), 115.8 (CH), 116.1 (CH), 118.3 (CH), 127.3
a yellow solid in an 86% yield. Mp 173 ꢀC; IR:
n
(cmꢁ1) 305, 1626,
(CH), 128.3 (CH), 128.6 (C), 133.9 (C), 140.5 (C), 160.2 (CH); MS (CIþ)
m/z 228 (MþC2H5þ), 200 (MHþ); HRMS (CIþ) calcd for C11H9N3O
(MHþ) 200.0824, found 200.0824.
1548, 1521, 1402, 1387, 1333, 1211, 1117, 791, 730, 677; 1H NMR
(CDCl3)
7.29 (dd, J¼4.1 and 7.0 Hz, 1H), 7.48 (dd, J¼4.1 and 8.8 Hz,
d

9572
C. Nyffenegger et al. / Tetrahedron 64 (2008) 9567–9573
4.4.7. Pyrazolo[1,5-a:3,4-c0]dipyridine 2g
J¼2.6 Hz, 1H), 9.64 (d, J¼9.8 Hz, 1H); 13C NMR (CDCl3)
d 16.2 (CH3),
Total reaction time: 12 min. The title compound was isolated as
a rust solid in a 71% yield. Mp 140 ꢀC; IR: (cmꢁ1) 3038, 2983, 1588,
1458, 1339, 1285, 1220, 1141, 1023, 805, 779, 747, 725, 680; 1H NMR
(CDCl3)
7.28–7.47 (m, 2H), 7.89 (dd, J¼1.2 and 5.7 Hz, 1H), 8.16 (d,
16.3 (CH3), 53.66 (OCH3), 63.0 (CH2), 63.1 (CH2), 63.7 (CH2), 63.8
(CH2), 106.4 (CH), 108.8 (CH), 121.0 (C), 128.5 (CH), 132.0 (CH), 134.3
(C), 140.4 (CH), 156.7 (C); MS (CIþ) m/z 355 (MþC2H5þ), 327 (MHþ);
HRMS (CIþ) calcd for (MHþ) 327.1226, found 327.1226.
n
d
J¼8.6 Hz, 1H), 8.36 (d, J¼5.7 Hz, 1H), 8.82 (d, J¼6.8 Hz, 1H), 9.38 (d,
J¼1.2 Hz, 1H); 13C NMR (CDCl3)
d 113.5 (CH), 118.4 (C), 118.6 (CH),
Acknowledgements
119.4 (CH), 123.0 (CH), 128.8 (CH), 134.9 (C), 137.1 (CH), 142.1 (CH),
145.7 (C); MS (CIþ) m/z 198 (MþC2H5þ), 170 (MHþ); HRMS (CIþ)
calcd for C10H7N3 (MHþ) 170.0718, found 170.0714.
The authors wish to thank the NMR team of CEA Le Ripault for
their assistance and the Unite´ de Chimie Organique Mole´culaire et
´
´
Macromoleculaire (UCO2MdUniversite du Maine) for performing
4.4.8. Pyrazolo[10,20:2,3][1,2,3]triazolo[4,5-b]pyridin-6-ium-5-ide 4a
the HRMS analyses.
Total reaction time: 12 min. The title compound was isolated as
a yellow solid in an 85% yield. Mp 162 ꢀC; IR:
n
(cmꢁ1) 3109, 1582,
Supplementary data
1518, 1481, 1384, 1313, 1266, 1233, 780, 745, 702; 1H NMR (CDCl3)
6.83 (t, J¼3.0 Hz, 1H), 7.29 (dd, J¼4.6 and 8.4 Hz, 1H), 7.65 (d,
d
Crystallographic data (excluding structure factors) for the
structures in this paper have been deposited with the Cambridge
Crystallographic Data Centre (CCDC) nos. 679154 and 679155 for
compound 2a and 4c, respectively. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: þ44 (0)1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk). The crystallographic data is available free
of charge in the online version. Supplementary data associated
with this article can be found in the online version, at doi:10.1016/
j.tet.2008.07.055.
J¼2.6 Hz, 1H), 7.69 (dd, J¼1.2 and 8.4 Hz, 1H), 7.93 (d, J¼3.2 Hz, 1H),
8.00 (dd, J¼1.2 and 4.6 Hz, 1H); 13C NMR (CDCl3)
d 105.7 (CH), 106.4
(CH), 109.7 (CH), 119.5 (CH), 122.2 (CH), 134.4 (C), 136.6 (CH), 140.4
(C); 15N NMR (CDCl3)
d
ꢁ122.1, ꢁ122.4, ꢁ162.97, ꢁ172.0; MS (CIþ)
m/z 159 (MHþ),132 (MHþꢁN2); HRMS (CIþ) calcd for C8H6N4 (MHþ)
159.0671, found 159.0667.
4.4.9. 7,9-Dimethylpyrazolo[10,20:2,3][1,2,3]triazolo[4,5-b]-
pyridin-6-ium-5-ide 4b
Total reaction time: 12 min. The title compound was isolated as
a yellow solid in a 92% yield. Mp 83 ꢀC; IR:
n
(cmꢁ1) 1583, 1505,
1470, 1343, 1305, 1258, 1032, 845, 768, 743, 675; 1H NMR (CDCl3)
References and notes
d
2.76 (s, 3H), 2.91(s, 3H), 6.46 (s, 1H), 7.39 (dd, J¼4.8 Hz and
1. (a) Uesaka, N.; Imma, H.; Kashima, H.; Kurokawa, M.; Nonaka, H.; Kanda, T.;
Kuwana, Y.; Toki, S.; Shimada, J. PCT Int. Appl., WO 2003028732 A1, 2003; Chem.
Abstr. 2003, 138, 304303; (b) Uesaka, N.; Shiozaki, S.; Saki, M.; Kanda, T.; Ichi-
mura, M.; Kuwana, Y.; Shimada, J. PCT Int. Appl., WO 2002079204 A1, 2002;
Chem. Abstr. 2002, 137, 294970; (c) Loones, K. T. J.; Herrebout, W. A.; Dommisse,
R. A.; Lemie`re, G. L. F.; Van der Veken, B. Tetrahedron 2007, 63, 3818–3825; (d)
Iwaki, T.; Yasuhara, A.; Sakamoto, T. J. Chem. Soc., Perkin Trans. 1 1999, 1505–
1510; (e) Leroy, M. G.; Fan, P. C.; Ablordeppey, S. Y.; Nimrod, A.; Clark, A. M. Med.
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2004, 29, 81–92; (b) Sikder, A. K.; Sikder, N. J. Hazard. Mater. 2004, A112, 1–15.
3. (a) Attanasi, O. A.; De Crescentini, L.; Filippone, P.; Mantellini, F.; Perrulli, F. R.;
Santeusanio, S. Synlett 2006, 1734–1738; (b) Loones, K. T. J.; Maes, B. U. W.;
J¼8.2 Hz, 1H), 7.83 (d, J¼8.2 Hz, 1H), 8.17 (d, J¼4.8 Hz, 1H); 13C NMR
(CDCl3)
d 10.3 (CH3), 11.3 (CH3), 108.2 (CH), 115.7 (C), 117.4 (CH),
120.0 (C), 121.6 (CH), 134.9 (CH), 136.7 (C), 141.1 (C); MS (CIþ) m/z
214 (MþC2Hþ5 ), 187 (MHþ); HRMS (CIþ) calcd for C10H10N4 (MHþ)
187.0984, found 187.0990.
4.4.10. 7-(Trifluoromethyl)pyrazolo[10,20:2,3][1,2,3]triazolo-
[4,5-b]pyridin-6-ium-5-ide 4c
Total reaction time: 12 min. The title compound was isolated as
an ivory solid in an 82% yield. Mp 209 ꢀC; IR:
n
(cmꢁ1) 3117, 1529,
`
´
Dommisse, R. A.; Lemiere, G. L. F. Chem. Commun. 2004, 2466–2467; (c) Sabatie,
A.; Ve´gh, D.; Loupy, A.; Floch, L. Arkivoc 2001, vi, 123–128; (d) Abbas, I. M.;
Riyadh, S. M.; Abdallah, M. A.; Gomha, S. M. J. Heterocycl. Chem. 2006, 43, 935–
942.
1388, 1294, 1261, 1198, 1105, 1081, 961, 817, 791, 750, 721, 712, 656;
1H NMR (CDCl3)
d
7.12 (d, J¼3.5 Hz, 1H), 7.43 (dd, J¼4.6 and 8.5 Hz,
1H), 7.94 (m, 2H), 8.22 (dd, J¼4.6 Hz, 1H); 13C NMR (CDCl3)
d 105.7
4. (a) Nyffenegger, C.; Fournet, G.; Joseph, B. Tetrahedron Lett. 2007, 48, 5069–
5072; (b) Aillaud, I.; Bossharth, E.; Conreaux, D.; Desbordes, P.; Monteiro, N.;
Balme, G. Org. Lett. 2006, 8, 1113–1116.
5. Sawant, D.; Kumar, R.; Maulik, P. R.; Kundu, B. Org. Lett. 2006, 8, 1525–1528.
6. Garnier, E.; Suzenet, F.; Poullain, D.; Lebret, B.; Guillaumet, G. Synlett 2006, 472–
474.
(CH), 107.1 (q, J¼47.3 Hz, C, C–CF3), 109.1 (CH), 120.4 (q, J¼265 Hz, C,
CF3), 122.2 (CH), 122.9 (CH), 134.1 (C), 139.8 (C), 139.9 (CH); MS (CIꢁ)
m/z 226 (M). Anal. Calcd for C9H5F3N4: C 47.80%; H 2.23%; N 24.77%.
Found: C 47.66%; H 2.71%; N 24.78%.
7. Garnier, E.; Audoux, J.; Pasquinet, E.; Suzenet, F.; Poullain, D.; Lebret, B.; Guil-
laumet, G. J. Org. Chem. 2004, 69, 7809–7815.
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4.4.11. Pyrazolo[10,20:1,2][1,2,3]triazolo[4,5-c]pyridin-9-
ium-10-ide 4e
Total reaction time: 50 min at 105 ꢀC. The title compound was
9. (a) Abramovitch, R. A.; Adams, K. A. H. Can. J. Chem. 1961, 39, 2516–2528; (b)
Abramovitch, R. A.; Kalinowski, J. J. Heterocycl. Chem. 1974, 11, 857–861.
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Meth-Cohn, O. J. Chem. Soc., Perkin Trans. 1 1980, 2387–2391; (f) Scriven, E. F. V.
Azides and Nitrenes; Academic: Orlando, 1984; (g) Scriven, E. F. V. Chem. Rev.
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311–323.
isolated as an orange solid in a 20% yield. Mp 161 ꢀC; IR:
n )
(cmꢁ1
3139, 1571, 1524, 1439, 1376, 1322, 1291, 1247, 1025, 782, 702; 1H
NMR (CDCl3)
6.96 (dd, J¼2.8 and 3.1 Hz,1H), 7.63 (d, J¼5.5 Hz,1H),
7.73 (d, J¼2.8 Hz, 1H), 7.80 (d, J¼3.1 Hz, 1H), 8.22 (d, J¼5.5 Hz, 1H),
d
8.96 (s, 1H); 13C NMR (CDCl3)
d 104.8 (CH), 105.2 (CH), 106.7 (CH),
110.8 (CH), 123.5 (C), 134.5 (CH), 135.9 (CH), 143.8 (C); MS (CIꢁ) m/z
159 (M); HRMS (CIþ) calcd for C8H6N4 (MHþ) 159,0671, found
159.0669.
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4.4.12. Diethyl [6-methoxy-2-(1H-pyrazol-1-yl)pyridin-3-yl]-
amidophosphate 5
Total reaction time: 24 min. The title compound was isolated as
a brown oil in a 35% yield. IR:
n
(cmꢁ1) 2984, 1490, 1439, 1402, 1256,
1017, 965, 916, 797, 762; 1H NMR (CDCl3)
d
1.24–1.34 (m, 6H), 3.88
(s, 3H), 4.00–4.15 (m, 4H), 6.42 (dd, J¼1.8 and 2.6 Hz, 1H), 6.59 (d,
J¼8.8 Hz, 1H), 7.68 (d, J¼1.8 Hz, 1H), 7.78 (d, J¼8.8 Hz, 1H), 8.53 (d,

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