Synthesis of new-type 1,3,6-triazocine via intramolecular reactions of iodocyclization and [3+2] azido cycloaddition

Article abstract of DOI:10.1002/jhet.4028

Selective iodocyclization of 6-(alkenylamino)-1-allylpyrazolo[3,4-d]pyrimidines provided hydrogenated derivatives of 1-allyl-8(9)-iodomethylimidazo(pyrimido)[1,2-a]pyrazolo[4,3-e]pyrimidines which were further reacted with NaN₃ at 75°С to 80°С to give a series of new-type 1,3,6-triazocines annulated with the pyrazole, pyrimidine, imidazole (or pyrimidine), and 1,2,3-triazole rings. The compounds synthesized were structurally characterized by analytical, spectral (IR, ¹H and ¹³C NMR, HPLC-mass), and X-ray diffraction data.

Full text of DOI:10.1002/jhet.4028

Received: 30 March 2020
DOI: 10.1002/jhet.4028
Revised: 29 April 2020
Accepted: 10 May 2020
A R T I C L E
Synthesis of new-type 1,3,6-triazocine via intramolecular
reactions of iodocyclization and [3+2] azido cycloaddition
Ruslan I. Vaskevych1,2
| Alla I. Vaskevych1,3 | Eduard B. Rusanov1
|
Oksana Ya. Mel'nyk4 | Mykhailo V. Vovk1
1Institute of Organic Chemistry, National
Abstract
Academy of Sciences of Ukraine,
Department of mechanisms of organic
reaction, Kyiv, Ukraine
2“Enamine Ltd” Scientific Production
Selective iodocyclization of 6-(alkenylamino)-1-allylpyrazolo[3,4-d]pyrimidines
provided hydrogenated derivatives of 1-allyl-8(9)-iodomethylimidazo(pyrimido)
[1,2-a]pyrazolo[4,3-e]pyrimidines which were further reacted with NaN3 at
75ꢀС to 80ꢀС to give a series of new-type 1,3,6-triazocines annulated with the
pyrazole, pyrimidine, imidazole (or pyrimidine), and 1,2,3-triazole rings. The
compounds synthesized were structurally characterized by analytical, spectral
(IR, 1H and 13C NMR, HPLC-mass), and X-ray diffraction data.
Association, Kyiv, Ukraine
3National Technical University of Ukraine
“Igor Sikorsky Kyiv Polytechnic Institute”,
Faculty of Chemical Technology,
Department of Physical Chemistry, Kyiv,
Ukraine
4Ivano-Frankivsk National Medical
University, Faculty of Pharmacy,
Department of Chemistry, Ivano-
Frankivsk, Ukraine
Correspondence
Ruslan I. Vaskevych, Institute of Organic
Chemistry, National Academy of Sciences
of Ukraine, Department of Mechanisms of
Organic Reaction, Murmanska str. 5, Kyiv
02660, Ukraine.
Email: r_vaskevich@ukr.net
1 | INTRODUCTION
These compounds contain the 1,3,6-triazocine core
annulated with the benzimidazole[14,15] or pyridotriazine
The literature on triheteroatomic eight-membered het-
erocycles mainly refers to ring structures with various
combinations of nitrogen, oxygen, and sulfur atoms.[1]
They are notable for their broad synthetic potential,
peculiar structural features, and pronounced biological
activity. A special place in this class of medium-sized het-
erocycles is occupied by triazocines which may be consid-
ered aza homologues of diazepines, well-known
pharmacological agents.[2] However, triazocines have
been much less studied, with few reported examples
bearing nitrogen atoms at ring positions 1,2,4,[3–6]
1,2,5,[7–9] 1,3,5,[10–13] and 1,3,6.[14–20] Particularly worthy
of attention are fused 1,3,6-triazocines some of which
ring,[20] or with the benzene, pyrrole, and pyrazole rings
together.[16]
We find it challenging to develop a facile route to
new polyheterocyclic systems in which the edges of the
1,3,6-triazocine core are fused the pyrazole, pyrimidine,
imidazoline (or dihydropyrimidine), and 1,2,3-triazoline
moieties. The synthetic strategy proposed in the present
study is based on two intramolecular processes, electro-
philic iodocyclization and the following [3+2] cycloaddi-
tion of the in situ generated azido function to the allyl
double bond.
Iodine-mediated reactions of functional unsaturated
compounds offer a powerful tool to efficiently construct
various mono and fused heterocyclic molecules.[21,22]
This promising field of reactions is exemplified by the
show
promise
as
potential
antiallergens,[14,15]
anticonvulsants,[16] and HIV integrase inhibitors.[20]
J Heterocyclic Chem. 2020;1–11.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals LLC.
1

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VASKEVYCH ET AL.
intramolecular iodocyclization of fused 2-(alkenylamino)
is converted to 1-allyl-8-iodomethyl-7,8-dihydro-1Н-
imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(6Н)-one 6а in
86% yield. The iodine-induced cyclization of
6-alkenylamino derivatives 4b-е into pentaiodides 5b-е
proceeds likewise in 92% to 99% yields. Bases 6с,e are
obtained in the same way as 6а, whereas their analogues
6b,d turn out to more efficiently result from the treat-
ment of salts 5b,d with the equivalent amount of NaI and
AcONa (Scheme 2).
The angular structure of tricyclic fused heterocycles
6a-e which implies the presence of the conjugated bonds
O C N C < in the pyrimidone ring is supported by the
reduced frequencies (1646-1651 cm−1) of the carbonyl
stretching vibrations in the IR spectra. The 13С NMR
chemical shift of the carbonyl carbon atom is observed to
be 163 to 167 ppm.[24]
pyrimidones
which
affords
the
corresponding
iodomethyl-functionalized imidazo and pyrimido
annulated cores[23–26]; the following nucleophilic substi-
tution of the iodine atom leads to azidomethyl derivatives
further converted to amines and 1,2,3-triazoles via cyclo-
addition reactions.[25] However, there is little available
information on intramolecular azido-to-alkenyl [3+2]
cycloadditions and mainly on those occurring in the
benzene,[27] indole,[28] and azetidinone derivatives.[29]
Here we aim to design the substrate molecules so that
the azidomethyl and allyl groups undergoing cycloaddi-
tion are the substituents on different moieties of the fused
polyheterocyclic core.
2 | RESULTS AND DISCUSSION
As the next step in the design of target molecules, we
converted iodine-containing heterocycles 6a-e to the
corresponding azido derivatives 7 which then spontane-
ously cyclized in situ (Scheme 3). As established in the
study of this reaction, all mentioned substrates in DMF
solution are inert towards NaN3 at room temperature but
6a-e enter into the reaction on heating the reaction mix-
ture to 75ꢀС to 80ꢀС. Finally, intermediates 7а-е undergo
the intramolecular [3+2] cycloaddition of the azido func-
tion to the allyl double bond to produce new-type poly-
heteroannulated[1,2,3]triazolo[5,1-e][1,3,6]triazocines 8а-е
in 67% to 91% isolated yield.
As key substrates for the intramolecular cyclizations to
yield target polyheteroannulated 1,3,6-triazocines, we
chose 6-(alkenylamino)-1-allyl-1,5-dihydro-4Н-pyrazolo
[3,4-d]pyrimidin-4-ones 4а-e (Scheme 1, Table 1) synthe-
sized from the corresponding 6-chloro derivative 2 by
reactions with allylamine 3a, N-methylallylamine 3b,
diallylamine 3c, 2-methylprop-2-en-1-amine 3d, and but-
3-en-1-amine 3e. In turn, compound 2 was obtained by
alkaline hydrolysis of 1-allyl-4,6-dichloro-1H-pyrazolo
[3,4-d]pyrimidine
1
which resulted from the
cyclocondensation
of
2,4,6-trichloropyrimidine-
The structure of the newly synthesized fused poly-
heterocyclic systems 8a-e correlates well to their mea-
sured physicochemical parameters, with the most reliable
structural characterization provided by the X-ray diffrac-
tion study of compound 8а (see Experimental) (Figure 1).
Structural parameters for 8а (bond distances and
angles) are as expected and in acceptable agreement with
the structural formula of the compound. For example
geometric parameters for atoms in heterocyclic system
N1 N5; C1 C5 are typical for conjugated systems, thus
bond lengths have intermediate values between single
and double C C, C N and N N bonds. The atoms
5-carbaldehyde[30] with allylhydrazine.
Pyrazolopyrimidones 4a-e contain two alkene sites
which can potentially be attacked by electrophilic
reagents, with the double bond in the alkenylamino moi-
ety appearing more reactive. As an example, the reaction
of compound 4а with a 3-fold excess of iodine in acetic
acid involves only the 6-alkenylamino substituent and
proceeds as an intramolecular iodocyclization to give
salt-like pentaiodide 5а which is almost quantitatively
isolated from the reaction mixture in an analytically pure
state. By treating this product with Na2SO3 in acetone, it
n
Cl
O
NH
R1
O
R2
N
NH
NH
NaOH
3a-e
N
N
N
n
N
N
N
N
Cl
N
N
N
Cl
R2
R1
1
4a-e
2
SCHEME 1 Synthesis of 6-(alkenylamino)-1-allyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones 4a-e

VASKEVYCH ET AL.
3
TABLE 1 Yields of products 4a-e, 5a-e, 6a-e, 8a-e
Entry
1
Product
4a
n
1
1
1
1
2
1
1
1
1
2
1
1
1
1
2
1
1
1
1
2
R1
R2
H
Yield (%)
78
H
2
4b
4c
CH3
H
98
3
CH2 CH CH2
H
67
4
4d
4e
H
CH3
H
92
5
H
74
6
5a
H
H
95
7
5b
5c
CH3
H
99
8
CH2 CH CH2
H
99
9
5d
5e
H
CH3
H
94
10
11
12
13
14
15
16
17
18
19
20
H
92
6a
H
H
86
6b
6c
CH3
H
81
CH2 CH CH2
H
84
6d
6e
H
CH3
H
79
H
74
8a
H
H
91
8b
8c
CH3
H
85
CH2 CH CH2
H
81
8d
8e
H
H
CH3
H
67
74
O
O
N
Na2SO3 or
NaI / AcONa
3I2
AcOH
NH
N
-
4a-e
N
I5
N
R1
R1
N
N+
N
N
N
n
n
R2
R2
I
I
5a-e
6a-e
SCHEME 2 Synthesis of iodomethyl substituted compounds 5a-e and 6a-e
N1 N5 and C1 C6 located in the plane with rms devia-
tion of fitted atoms of 0.040 and atom C7 has deviation
from that plane for 0.172(4)Å, thus the corresponding
dihedral angles N4C4N5C7, N3C4N5C7, C7C6N3C3 and
C7C6N3C4 are −168.9(3), 10.9(3), 177.5(3) and −16.0(3)ꢀ
respectively. The five membered cycle N6N7N8C10C11 is
non-planar with maximum deviation atoms of 0.100(2)Å
and it has envelope conformation with dihedral angle
between planes N6N7N8C11 and N6C10C11 of 16.3(3)ꢀ.
The eight-membered ring in the compound 8а adopts a
non-planar conformation, as expected, and it has wrap
around conformation. All atoms of the eight-membered
ring lie in three (I-III) planes N2N3C3C6C9, C6C8C9C10,
N6C8C10, and rms deviation of fitted atoms in
corresponding planes of 0.0245, 0.0220 and 0.0. The dihe-
dral angles between least-squares planes I-II and II-III
are 66.0(1)ꢀ and 54.1(3)ꢀ respectively. The conformation
of eight-membered ring are shown on Figure 2.

4
VASKEVYCH ET AL.
O
N
O
N
N
N
NaN3
N
N
6a-e
DMF, 75-80oC
R1
N
R1
N
N
n
N
n
R2
R2
N
N3
N
N
7a-e
8a-e
SCHEME 3 Synthesis of polyheteroannulated 1,3,6-triazocines 8a-e
FIGURE 1 Molecular structure of
8а. Thermal ellipsoids are drawn at 50%
probability level
3 | CONCLUSION
4 | EXPERIMENTAL
We have developed an efficient access to new-type
1,3,6-triazocine scaffolds annulated with four, five- and six-
membered heterocyclic systems. The proposed strategy
involves, as key steps, two successive intramolecular conver-
sions of 6-(alkenylamino)-1-allylpyrazolo[3,4-d]pyrimidines,
viz., iodocyclization and azido-to-allyl [3+2] cycloaddition.
The
starting
material,
2,4,6-trichloropyrimidine-
5-carbaldehyde, was prepared by the literature proce-
dure.[30] The IR spectra of the compounds obtained were
recorded on a Bruker Vertex 70 spectrometer in KBr pel-
lets. The H and 13C NMR spectra were acquired on a
1
Varian VXR-400 (400 and 100 MHz, respectively), Bruker

VASKEVYCH ET AL.
5
FIGURE 2 Conformation of eight-
membered cycle in compound 8a.
Thermal ellipsoids are drawn at 50%
probability level
Avance 500 (500 and 125 MHz respectively) and Bruker
Avance 600 (600 and 150 MHz respectively) instrument
in DMSO-d6 solutions, with TMS as internal standard.
The LC/MS spectra were recorded on an Agilent 1100
Series high-performance liquid chromatograph interfaced
with an Agilent G1956B single quadrupole mass
spectrometer.
19.51 g (71%). The physicochemical characteristics of the
product are as previously reported.[31]
4.2 | 6-Сhloro-1-(prop-2-enyl)-
1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-
4-one (2)
To a 135ꢀС to 140ꢀС heated solution of NaOH (20 g,
0.5 mol) in water (200 mL), compound 1 (20 g, 0.087 mol)
was added and boiled until completely dissolved. Then
activated carbon (1 g) was added to the reaction mixture,
followed by boiling it for another 10 minutes, cooling to
40ꢀС to 60ꢀС, and filtering off the carbon. The filtrate
was acidified with concentrated acetic acid to рН 3 to
4 and the resulting precipitate was filtered off, washed
with water (50 mL), and dried at 70ꢀС. Light yellow solid,
yield: 89%; m.p. 196ꢀС to 197ꢀС; IR (KBr) νmax (cm−1):
3090 (NH stretching), 2873 (CH stretching), 1718 (C O
4.1 | 4,6-Dichloro-1-(prop-2-enyl)-1H-
pyrazolo[3,4-d]pyrimidine (1)
To
a stirred solution of 2,4,6-trichloropyrimidine-
5-carbaldehyde (25.32 g, 0.12 mol) in methanol (200 mL)
was added at −20ꢀС allylhydrazine obtained from the
corresponding dihydrochloride (17.4 g, 0.12 mol) and
triethylamine (36.4 g, 0.36 mol) in methanol (250 mL).
The mixture was stirred at −20ꢀС for 1 hour and then at
0ꢀС for 2 hours, followed by standing at 0ꢀС overnight.
Methanol was removed and the residue was extracted
with ethyl acetate (400 mL), evaporated, and purified by
flash chromatography with chloroform as eluent. Yield
1
stretching), 1581 (C N stretching); Н NMR (400 MHz,
DMSO-d6): δ 4.86 (d, J = 5.2 Hz, 2H, СН2), 5.02 (d,
J = 18.4 Hz, 1H, СН), 5.18 (d, J = 9.2 Hz, 1H, СН),

6
VASKEVYCH ET AL.
5.95 to 6.02 (m, 1Н, СН), 8.10 (s, 1Н, CН pyrazole),
13.12 to 13.37 (m, 1Н, NH); MS: m/z 211 (M + H); Anal.
Calcd for C8H7ClN4О: C, 45.62; H, 3.35; Cl, 16.83; N,
26.60; found: C, 45.56; H, 3.24; Cl, 16.77; N, 25.95.
246 (M + H); Anal. Calcd for C12H15N5О: C, 58.76; H,
6.16; N, 28.55; found: C, 58.66; H, 6.13; N, 28.49.
4.3.3 | 6-(Diprop-2-enylamino)-1-(prop-
2-enyl)-1,5-dihydro-4H-pyrazolo[3,4-d]
pyrimidin-4-one (4c)
4.3 | General procedure for the synthesis
of compounds (4a-e)
White solid, m.p. 119ꢀС to 121ꢀС; IR (KBr) νmax (cm−1):
3188 (NH stretching), 1675 (C O stretching), 1571 (C N
stretching); 1Н NMR (400 MHz, DMSO-d6): δ 4.15 (d,
J = 4.8 Hz, 4Н, 2СН2), 4.71 (d, J = 5.2 Hz, 2Н, СН2), 5.05
(d, J = 18.4 Hz, 1Н, СН), 5.14 to 5.20 (m, 5Н, 5 СН),
5.78 to 5.88 (m, 2Н, 2 СН), 5.91 to 6.01 (m, 1Н, СН),
7.79 (s, 1Н, CН pyrazole), 10.59 to 10.62 (m, 1Н, NH); 13C
NMR (150 MHz, DMSO-d6): δ 48.9, 49.9, 99.3, 117.4,
117.7, 133.6, 133.8, 134.7, 153.2, 154.2, 158.9; MS: m/z
272 (M + H); Anal. Calcd for C14H17N5О: C, 61.98; H,
6.32; N, 25.81; found: C, 61.89; H, 6.27; N, 25.80.
A mixture of compound 2 (5.27 g, 25 mmol), amine 3a-d
(25 mmol) or amine hydrochloride 3e (2.69 g, 25 mmol),
and triethylamine (2.53 g, 25 mmol or 5.06 g, 50 mmol
for 3e) was boiled in ethanol (100 mL) for 4 hours. After
the solvent was removed, water (50 mL) was added to the
residue. The resulting solid precipitate was filtered off,
washed with 5ꢀС cooled ethanol (10 mL) and diethyl
ether (10 mL), and purified by recrystallization from
ethanol.
4.3.1 | 1-(Prop-2-enyl)-6-(prop-
2-enylamino)-1,5-dihydro-4H-pyrazolo
[3,4-d]pyrimidin-4-one (4a)
4.3.4 | 6-[(2-Methylprop-2-enyl)amino]-
1-(prop-2-enyl)-1,5-dihydro-4H-pyrazolo
[3,4-d]pyrimidin-4-one (4d)
White solid, m.p. 178ꢀС to 179ꢀС; IR (KBr) νmax (cm−1):
3393 (NH stretching), 2843 (CH stretching), 1699 (C O
White solid, m.p. 159ꢀС to 161ꢀС; IR (KBr) νmax (cm−1):
1
stretching), 1618 (C N stretching); Н NMR (400 MHz,
3395 (NH stretching), 2845 (CH stretching), 1692 (C O
1
DMSO-d6): δ 3.95 (t, J = 5.6 Hz, 2Н, СН2), 4.70 (d,
J = 5.2 Hz, 2Н, СН2), 5.02 (dd, J1 = 16.8 Hz, J2 = 1.6 Hz,
1Н, СН), 5.13 (dd, J1 = 10.4 Hz, J2 = 1.6 Hz, 2Н,
stretching), 1619 (C N stretching); Н NMR (400 MHz,
DMSO-d6): δ 1.72 (s, 3Н, СН3), 3.89 (d, J = 5.6 Hz, 2Н,
СН2), 4.69 (d, J = 5.2 Hz, 2Н, СН2), 4.85 (d, J = 17.6 Hz,
2Н, СН2), 5.04 (d, J = 17.2 Hz, 1Н, СН), 5.14 (d,
J = 9.2 Hz, 1Н, СН), 5.90 to 6.03 (m, 1Н, СН), 6.67 to
6.73 (m, 1Н, NH), 7.77 (s, 1Н, CН pyrazole), 10.32 to
10.51 (m, 1Н, NH); 13C NMR (125 MHz, DMSO-d6): δ
20.8; 46.1, 48.9, 100.1, 110.9, 117.7, 133.9, 134.8, 142.6,
154.0, 154.6, 158.2; MS: m/z 246 (M + H); Anal. Calcd for
C12H15N5О: C, 58.76; H, 6.16; N, 28.55; found: C,
58.68; H, 6.15; N, 28.52.
2
СН), 5.22 (dd, J1 = 17.2 Hz, J2 = 2.0 Hz, 1Н, СН),
5.87 to 6.00 (m, 1Н, СН), 6.64 to 6.71 (m, 1Н, NH), 7.78
(s, 1Н, CН pyrazole), 10.48 to 10.51 (m, 1Н, NH); 13C
NMR (150 MHz, DMSO-d6): δ 43.0, 48.8, 100.0, 116.2,
117.6, 133.8, 134.8, 135.2, 153.8, 154.5, 158.2; MS: m/z
232 (M + H); Anal. Calcd for C11H13N5О: C, 57.13; H,
5.67; N, 30.28; found: C, 57.06; H, 5.62; N, 30.25.
4.3.2 | 6-[Methyl(prop-2-enyl)amino]-
1-(prop-2-enyl)-1,5-dihydro-4H-pyrazolo
[3,4-d]pyrimidin-4-one (4b)
4.3.5 | 6-(But-3-enylamino)-1-(prop-
2-enyl)-1,5-dihydro-4H-pyrazolo[3,4-d]
pyrimidin-4-one (4e)
White solid, m.p. 143ꢀС to 145ꢀС; IR (KBr) νmax (cm−1):
3202 (NH stretching), 2934 (CH stretching), 1674 (C O
White solid, m.p. 143ꢀС to 145ꢀС; IR (KBr) νmax (cm−1):
1
stretching), 1591 (C N stretching); Н NMR (400 MHz,
3398 (NH stretching), 2847 (CH stretching), 1699 (C O
1
DMSO-d6): δ 3.04 (s, 3Н, СН3), 4.18 (d, J = 5.6 Hz, 2Н,
СН2), 4.70 (d, J = 5.2 Hz, 2Н, СН2), 5.03 (d, J = 17.2 Hz,
1Н, СН), 5.13 to 5.18 (m, 3Н, 3 СН), 5.77 to 5.87 (m,
1Н, СН), 5.91 to 6.00 м (m, 1Н, СН), 7.79 (s, 1Н, CН
pyrazole), 10.66 to 10.69 (m, 1Н, NH); 13C NMR
(125 MHz, DMSO-d6): δ 35.9, 48.8, 52.0; 99.2, 117.4,
117.6, 133.4, 133.9, 134.7, 153.8, 154.3, 159.0; MS: m/z
stretching), 1620 (C N stretching); Н NMR (400 MHz,
DMSO-d6): δ 2.30 (q, J = 6.8 Hz, 2Н, СН2), 3.38 (q,
J = 6.8 Hz, 2Н, СН2), 4.71 (d, J = 5.2 Hz, 2Н, СН2), 5.03
(d, J = 8.0 Hz, 1Н, СН), 5.06 to 5.16 (m, 3Н, 3 СН),
5.77 to 5.87 (m, 1Н, СН), 5.92 to 6.02 (m, 1Н, СН),
6.44 to 6.50 (m, 1Н, NH), 7.75 (s, 1Н, CН pyrazole), 10.39
to 10.41 (m, 1Н, NH); 13C NMR (125 MHz, DMSO-d6): δ

VASKEVYCH ET AL.
7
33.4; 40.1, 48.8, 99.9, 117.2, 117.5, 133.9, 134.7, 136.2,
153.9, 154.6, 158.2; MS: m/z 246 (M + H); Anal. Calcd for
C12H15N5О: C, 58.76; H, 6.16; N, 28.55; found: C,
58.72; H, 6.14; N, 28.54.
4.4.3 | 8-(Iodomethyl)-4-oxo-1,6-di(prop-
2-enyl)-1,4,5,6,7,8-hexahydroimidazo[1,2-a]
pyrazolo[4,3-e]pyrimidin-9-ium
pentaiodide (5c)
Braun solid, m.p. 178ꢀС to 180ꢀС; IR (KBr) νmax (cm−1):
1703 (C O stretching), 1660 (C N+ stretching), 1583
(C N+ stretching),; 1Н NMR (400 MHz, DMSO-d6): δ
3.55 to 3.70 (m, 3Н, 3СН), 4.04 to 4.09 (m, 1Н, СН), 4.17
to 4.28 (m, 2Н, 2СН), 4.83 to 4.88 (m, 1Н, СН), 5.03 to
5.07 (m, 2Н, 2СН), 5.28 (d, J = 10.0 Hz, 2Н, 2 СН), 5.34
(d, J = 10.8 Hz, 1Н, СН), 5.43 (d, J = 16.8 Hz, 1Н, СН),
5.83 to 5.93 (m, 1Н, СН), 6.02 to 6.11 (m, 1Н, СН), 8.11
(s, 1Н, CН pyrazole); 13C NMR (150 MHz, DMSO-d6): δ
8.6, 47.9, 52.7, 53.5, 57.0, 101.5, 118.5, 120.8, 130.4, 132.8,
137.8, 140.6, 152.6, 158.6; Anal. Calcd for
C14H17I6N5О: C, 16.28; H, 1.66; I, 73.73; N, 6.78;
found: C, 13.26; H, 1.29; I, 76.55; N, 7.02.
4.4 | General procedure for the synthesis
of compounds (5a-e)
To a stirred solution of compound 4а-е (9 mmol) in
acetic acid (30 mL), a solution of iodine (6.86 g,
27 mmol) in acetic acid (300 mL) was slowly added.
After 48 hours, the resulting salt-like precipitate was fil-
tered off, washed with acetic acid (50 mL) and hexane
(30 mL), and dried.
4.4.1 | 8-(Iodomethyl)-4-oxo-1-(prop-
2-enyl)-1,4,5,6,7,8-hexahydroimidazo[1,2-a]
pyrazolo[4,3-e]pyrimidin-9-ium
pentaiodide (5a)
4.4.4 | 8-(Iodomethyl)-8-methyl-4-oxo-
1-(prop-2-enyl)-
1,4,5,6,7,8-hexahydroimidazo[1,2-a]pyrazolo
[4,3-e]pyrimidin-9-ium pentaiodide (5d)
Braun solid, m.p. 173ꢀС to 175ꢀС; IR (KBr) νmax (cm−1):
1710 (C O stretching), 1671 (C N+ stretching), 1587
1
(C N stretching); Н NMR (400 MHz, DMSO-d6): δ 3.56
to 3.59 (m, 1Н, СН), 3.64 to 3.68 (m, 1Н, СН), 3.72 to 3.74
(m, 1Н, СН), 4.04 to 4.09 (m, 1Н, СН), 4.87 (d,
J = 21.0 Hz, 1Н, СН), 5.06 (d, J = 20.4 Hz, 2Н, СН2),
5.32 (d, J = 11.2 Hz, 1Н, СН), 5.35 to 5.36 (m, 1Н, СН),
6.02 to 6.11 (m, 1Н, СН), 8.17 (s, 1Н, CН pyrazole); 13C
NMR (125 MHz, DMSO-d6): δ 8.9, 49.7, 52.7, 58.5, 101.8,
118.5, 132.8, 138.1, 140.2, 153.4, 156.4; Anal. Calcd for
C11H13I6N5О: C, 13.31; H, 1.32; I, 76.70; N, 7.05;
found: C, 13.26; H, 1.29; I, 76.55; N, 7.02.
Braun solid, m.p. 143ꢀС to 145ꢀС; IR (KBr) νmax (cm−1):
3124 (NH stretching), 2886 (CH stretching), 1713 (C O
stretching), 1676 (C N+ stretching), 1580 (C N
1
stretching); Н NMR (400 MHz, DMSO-d6): δ 2.01 (s, 3Н,
СН3), 3.85 (q, J = 12.0 Hz, 2Н, СН2), 3.89 (s, 2Н, СН2),
4.81 (d, J = 17.6 Hz, 1Н, СН), 5.25 to 5.28 (m, 2Н, СН2),
5.26 (d, J = 10.8 Hz, 1Н, СН), 5.98 to 6.08 (m, 1Н,
СН), 8.22 (s, 1Н, CН pyrazole); 13C NMR (150 MHz,
DMSO-d6): δ 15.3, 25.6, 55.3, 57.7, 69.2; 103.0, 117.7,
132.8, 138.5, 140.9, 153.7, 156.6; Anal. Calcd for
C12H15I6N5О: C, 14.32; H, 1.50; I, 75.64; N, 6.96;
found: C, 14.29; H, 1.45; I, 75.58; N, 6.90.
4.4.2 | 8-(Iodomethyl)-6-methyl-4-oxo-
1-(prop-2-enyl)-
1,4,5,6,7,8-hexahydroimidazo[1,2-a]pyrazolo
[4,3-e]pyrimidin-9-ium pentaiodide (5b)
4.4.5 | 9-(Iodomethyl)-4-oxo-1-(prop-
2-enyl)-4,5,6,7,8,9-hexahydro-1H-pyrazolo
[4,3-e]pyrimido[1,2-a]pyrimidin-10-ium
pentaiodide (5e)
Braun solid, m.p. 172ꢀС to 174ꢀС; IR (KBr) νmax (cm−1):
1704 (C O stretching), 1676 (C N+ stretching), 1585
1
(C N stretching); Н NMR (400 MHz, DMSO-d6): δ 3.15
(s, 3Н, СН3), 3.53 to 3.55 (m, 1Н, СН), 3.60 to 3.63 (m, Н,
СН), 3.75 to 3.77 (m, Н, СН), 4.09 to 4.14 (m, 1Н, СН),
4.84 to 4.87 (m, 1Н, СН), 5.00 to 5.07 (m, 2Н, 2СН), 5.27
to 5.32 (m, 2Н, 2СН), 6.01 to 6.11 (m, 1Н, СН), 8.14 (s,
1Н, CН pyrazole); 13C NMR (125 MHz, DMSO-d6): δ 8.3,
32.9, 52.6, 55.7, 57.0; 101.4, 118.3, 132.8, 137.8, 140.5,
152.9, 158.4; Anal. Calcd for C12H15I6N5О: C, 14.32; H,
1.50; I, 75.64; N, 6.96; found: C, 14.27; H, 1.47; I,
75.53; N, 6.87.
Braun solid, m.p. 126ꢀС to 128ꢀС; IR (KBr) νmax (cm−1):
3156 (NH stretching), 2956 (CH stretching), 1700 (C O
stretching), 1657 (C N+ stretching), 1599 (C N
stretching); 1Н NMR (400 MHz, DMSO-d6): δ 2.16 to 2.25
(m, 1Н, СН), 2.40 to 2.45 (m, 1Н, СН), 3.46 to 3.55 (m,
2Н, СН2), 3.59 to 3.61 (m, 2Н, СН2), 4.84 to 4.90 (m, 1Н,
СН), 4.96 to 5.04 (m, 2Н, СН2), 5.21 to 5.26 (m, 1Н, СН),
5.31 (d, J = 10.8 Hz, 1Н, СН), 6.07 to 6.16 (m, 1Н,
СН), 8.15 (s, 1Н, CН pyrazole); 13C NMR (125 MHz,

8
VASKEVYCH ET AL.
DMSO-d6): δ 4.7; 21.2; 35.1; 53.7, 54.9, 103.8, 117.9, 133.2,
136.9, 141.8, 148.9, 155.6; Anal. Calcd for
C12H15I6N5О: C, 14.32; H, 1.50; I, 75.64; N, 6.96;
found: C, 14.30; H, 1.49; I, 75.61; N, 6.95.
(400 MHz, DMSO-d6): δ 2.93 (s, 3Н, СН3), 3.44 to 3.46 (m,
1Н, СН), 3.50 to 3.59 (m, 2Н, СН2), 3.88 to 3.93 (m, 1Н,
СН), 4.76 to 4.81 (m, 1Н, СН), 4.91 to 5.03 (m, 3Н,
СН2 + CH), 5.21 (d, J = 10.0 Hz, 1Н, СН), 6.00 to 6.10
(m, 1Н, СН), 7.79 (s, 1Н, CН pyrazole); 13C NMR
(125 MHz, DMSO-d6): δ 10.5, 31.5, 52.0, 53.4, 54.4, 103.3,
117.5, 133.7, 136.8, 141.6, 156.1, 166.3; MS: m/z 372 (M
+ H); Anal. Calcd for C12H14IN5О: C, 38.83; H, 3.80; I,
34.19; N, 18.87; found: C, 38.78; H, 3.76; I, 34.15; N, 18.79.
4.5 | General procedure for the synthesis
of compounds (6a,c,e)
To a stirred solution of compound 5a,c,e (7 mmol) in ace-
tone (30 mL), Na2SO3 (1.76 g, 14 mmol) in water (20 mL)
was added. After 2 hours, the resulting precipitate was fil-
tered off, washed with water (20 mL), ethanol (5 mL),
and hexane (20 mL), and then air-dried.
4.6.3 | 8-(Iodomethyl)-1,6-di(prop-
2-enyl)-7,8-dihydro-1H-imidazo[1,2-a]
pyrazolo[4,3-e]pyrimidin-4(6H)-one (6c)
White solid, m.p. 180ꢀС to 182ꢀС; IR (KBr) νmax (cm−1):
1
4.6 | General procedure for the synthesis
1647 (C O stretching), 1610 (C N stretching); Н NMR
of compounds (6b,d)
(400 MHz, DMSO-d6): δ 3.41 to 3.44 (m, 1Н, СН), 3.52 to
3.60 (m, 2Н, 2СН), 3.84 to 3.88 (m, 1Н, СН), 3.96 to 4.09
(m, 2Н, 2СН), 4.77 to 4.81 (m, 1Н, СН), 4.94 to 4.98 (m,
2Н, 2СН), 5.03 to 5.06 (m, 1Н, СН), 5.21 to 5.26 (m, 2Н,
To a stirred solution of compound 5b,d (7 mmol) in ace-
tone (30 mL), NaI (1.20 g, 8 mmol) in acetone (30 mL)
was added and the reaction mixture was stirred for 2 hours.
The resulting precipitate was filtered off and dissolved in
methanol (20 mL), followed by adding CH3COONa
(0.66 g, 8 mmol) to the stirred solution. After 8 hours, the
solvent was distilled off and the solid residue was treated
with water (20 mL), filtered off, and air-dried.
2
СН), 5.33 (d, J = 17.2 Hz, 1Н, СН), 5.81 to 5.90 (m,
1Н, СН), 6.00 to 6.10 (m, 1Н, СН), 7.80 (s, 1Н, CН
pyrazole); 13C NMR (125 MHz, DMSO-d6): δ 10.4, 47.0,
51.2, 52.1, 54.5, 103.7, 117.6, 119.0, 132.7, 133.7, 136.8,
141.6, 155.7, 166.2; MS: m/z 398 (M + H); Anal. Calcd for
C14H16IN5О: C, 42.33; H, 4.06; I, 31.95; N, 17.63;
found: C, 42.19; H, 4.03; I, 31.87; N, 17.55.
4.6.1 | 8-(Iodomethyl)-1-(prop-2-enyl)-
7,8-dihydro-1H-imidazo[1,2-a]pyrazolo
[4,3-e]pyrimidin-4(6H)-one (6a)
4.6.4 | 8-(Iodomethyl)-8-methyl-1-(prop-
2-enyl)-7,8-dihydro-1H-imidazo[1,2-a]
pyrazolo[4,3-e]pyrimidin-4(6H)-one (6d)
White solid, m.p. 145ꢀС to 148ꢀС; IR (KBr) νmax (cm−1):
3194 (NH stretching), 1646 (C O stretching), 1599 (C N
stretching); 1Н NMR (400 MHz, DMSO-d6): δ 3.43 to 3.58
(m, 3Н, 3СН), 3.81 to 3.86 (m, 1Н, СН), 4.78 (d,
J = 17.2 Hz, 1Н, СН), 4.95 (d, J = 16.8 Hz, 2Н, СН2),
5.05 to 5.08 (m, 1Н, СН), 5.23 (d, J = 10.4 Hz, 1Н, СН),
6.01 to 6.10 (m, 1Н, СН), 7.78 (s, 1Н, CН pyrazole), 8.41
to 8.48 (m, 1Н, NH); 13C NMR (125 MHz, DMSO-d6): δ
9.7, 46.6, 51.5, 56.0, 103.0, 117.1, 133.2, 136.3, 141.0,
157.3, 165.9; MS: m/z 358 (M + H); Anal. Calcd for
C11H12IN5О: C, 36.99; H, 3.39; I, 35.53; N, 19.61;
found: C, 36.88; H, 3.36; I, 35.51; N, 19.57.
White solid, m.p. 151ꢀС to 153ꢀС; IR (KBr) νmax (cm−1):
3201 (NH stretching), 1648 (C O stretching), 1584 (C N
1
stretching); Н NMR (400 MHz, DMSO-d6): δ 1.92 (s, 3Н,
СН3), 3.67 (q, J = 10.8 Hz, 2Н, СН2), 3.80 to 3.87 (m, 2Н,
СН2), 4.73 (d, J = 16.8 Hz, 1Н, СН), 5.02 to 5.06 (m, 2Н,
СН2), 5.22 (d, J = 9.6 Hz, 1Н, СН), 5.98 to 6.07 (m, 1Н,
СН), 7.96 (s, 1Н, CН pyrazole); 13C NMR (125 MHz,
DMSO-d6): δ 16.5, 25.9, 54.7, 56.4, 66.5, 104.2, 117.4,
133.4, 137.7, 141.8, 157.2, 163.6; MS: m/z 372 (M + H);
Anal. Calcd for C12H14IN5О: C, 38.83; H, 3.80; I, 34.19; N,
18.87; found: C, 38.79; H, 3.77; I, 34.13; N, 18.76.
4.6.2 | 8-(Iodomethyl)-6-methyl-1-(prop-
2-enyl)-7,8-dihydro-1H-imidazo[1,2-a]
pyrazolo[4,3-e]pyrimidin-4(6H)-one (6b)
4.6.5 | 9-(Iodomethyl)-1-(prop-2-enyl)-
6,7,8,9-tetrahydropyrazolo[4,3-e]pyrimido
[1,2-a]pyrimidin-4(1H)-one (6e)
White solid, m.p. 179ꢀС to 181ꢀС; IR (KBr) νmax (cm−1):
1651 (C O stretching), 1605 (C N stretching); Н NMR
White solid, m.p. 165ꢀС to 167ꢀС; IR (KBr) νmax (cm−1):
2870 (CH stretching), 1648 (C O stretching), 1625 (C N
1

VASKEVYCH ET AL.
9
stretching); 1Н NMR (400 MHz, DMSO-d6): δ 2.07 to 2.17
(m, 1Н, СН), 2.32 to 2.35 (m, 1Н, СН), 3.31 to 3.44 (m,
2Н, СН2), 3.51 to 3.62 (m, 2Н, СН2), 4.72 to 4.77 (m, 1Н,
СН), 4.39 to 4.45 (m, 1Н, СН), 4.75 to 4.80 (m, 1Н, СН),
5.32 to 5.38 (m, 1Н, СН), 7.59 (s, 1Н, CН pyrazole); 13C
NMR (125 MHz, DMSO-d6 + D2O): δ 31.6, 50.5, 51.2,
51.9, 52.3, 54.8, 69.0, 101.7, 136.1, 143.3, 155.8, 168.2;
Anal. Calcd for C12H14N8О: C, 50.34; H, 4.93; N, 39.14;
found: C, 50.26; H, 4.90; N, 39.12.
СН), 4.90 (d, J = 18.8 Hz, 2Н,
СН2), 5.13 (d,
J = 16.4 Hz, 1Н, СН), 5.25 (d, J = 11.2 Hz, 1Н, СН), 6.06
to 6.14 (m, 1Н, СН), 7.74 (s, 1Н, CН pyrazole), 8.64 to
9.02 (m, 1Н, NH); 13C NMR (100 MHz, DMSO-d6): δ 6.0,
22.6, 34.3, 52.8, 54.1, 105.9; 117.1, 134.1, 135.6, 142.6,
151.5, 164.3; MS: m/z 372 (M + H); Anal. Calcd for
C12H14IN5О: C, 38.83; H, 3.80; I, 34.19; N, 18.87;
found: C, 38.76; H, 3.77; I, 34.16; N, 18.75.
4.7.3 | (7aRS,11aSR)-2-allyl-1,2,7a,8,11,11a-
hexahydro-4H,7H-2,2a1,3,6,6a,9,10,10a-
octaazacyclopenta[6,7]cycloocta[1,2,3,4-jkl]-
as-indacen-4-one (8c)
4.7 | General procedure for the synthesis
of compounds (8a-е)
White solid, m.p. >300ꢀС; IR (KBr) νmax (cm−1): 1620
(C O stretching), 1588 (C N stretching); 1Н NMR
(400 MHz, DMSO-d6): δ 3.56 to 3.59 (m, 1Н, СН), 3.81 to
3.86 (m, 1Н, СН), 3.98 to 4.09 (m, 5Н, 5СН), 4.22 (d,
J = 15.6 Hz, 1Н, СН), 4.27 to 4.41 (m, 2Н, 2СН), 4.77 (d,
J = 16.0 Hz, 1Н, СН), 5.24 to 5.31 (m, 2Н, 2 СН), 5.34
to 5.41 (m, 1Н, СН), 5.82 to 5.91 (m, 1Н, СН), 7.61 (s,
1Н, CН pyrazole); 13C NMR (125 MHz, DMSO-d6): δ
46.7, 49.5, 50.7, 51.0, 52.2, 54.9, 69.7, 102.4, 118.7, 132.6,
136.0, 143.2, 155.2, 166.8; Anal. Calcd for C14H16N8О: C,
53.84; H, 5.16; N, 35.88; found: C, 53.77; H,
5.11; N, 35.83.
A mixture of iodomethyl derivative 6a-е (2 mmol) and
NaN3 (0.14 g, 2.15 mmol) in DMF (20 mL) was heated at
75ꢀС to 80ꢀС for 1.5 to 2 hours and then cooled. The
resulting precipitate was filtered off and washed with
diethyl ether (15 mL). After the filtrate was left to stand
for 2 to 3 days, an additional amount of the analytically
pure product precipitated which was then added to the
main portion of the target compound.
4.7.1 | (7aRS,11aSR)-1,2,7a,8,11,11a-
hexahydro-4H,7H-2,2a1,3,6,6a,9,10,10a-
octaazacyclopenta[6,7]cycloocta[1,2,3,4-jkl]-
as-indacen-4-one (8a)
4.7.4 | (7aRS,11aSR)-11a-methyl-
1,2,7a,8,11,11a-hexahydro-4H,7H-
2,2a1,3,6,6a,9,10,10a-octaazacyclopenta[6,7]
cycloocta[1,2,3,4-jkl]-as-indacen-4-one (8d)
White solid, m.p. >300ꢀС; IR (KBr) νmax (cm−1): 2802
(CH stretching), 1623 (C O stretching), 1591 (C N
stretching); 1Н NMR (400 MHz, DMSO-d6): δ 3.53 to 3.56
(m, 1Н, СН), 3.80 to 3.85 (m, 1Н, СН), 3.92 to 4.06 (m,
3Н, 3СН), 4.19 to 4.42 (m, 3Н, 3СН), 4.73 to 4.77 (m, 1Н,
СН), 5.31 to 5.39 (m, 1Н, СН), 7.60 (s, 1Н, CН pyrazole),
8.31 to 8.42 (m, 1Н, NH). 13C NMR (125 MHz, DMSO-
d6): δ 44.8, 50.2, 50.5, 53.3, 54.5, 69.2, 102.1, 135.4, 142.6,
156.9, 166.0; Anal. Calcd for C11H12N8О: C, 48.53; H,
4.44; N, 41.16; found: C, 48.47; H, 4.39; N, 41.06.
White solid, m.p. >300ꢀС (DMF); IR (KBr) νmax (cm−1):
3450 (NH stretching), 1649 (C O stretching), 1604 (C N
1
stretching); Н NMR (400 MHz, DMSO-d6): δ 1.63 (s, 3Н,
СН3), 3.63 to 3.66 (m, 1Н, СН), 3.70 to 3.76 (m, 1Н, СН),
3.80 to 3.82 (m, 1Н, СН), 3.99 to 4.04 (m, 1Н, СН), 4.14
(d, J = 16.0 Hz, 1Н, СН), 4.24 to 4.32 (m, 1Н, СН), 4.39 to
4.43 (m, 1Н, СН), 4.56 to 4.64 (m, 2Н, 2СН), 7.68 (s, 1Н,
CН pyrazole), 8.29 to 8.50 (m, 1Н, NH); 13C NMR
(125 MHz, DMSO-d6): δ 27.3, 52.2, 53.9, 54.5, 56.3, 65.4,
67.4, 105.0, 136.3, 142.1, 157.7, 166.1; Anal. Calcd for
C12H14N8О: C, 50.34; H, 4.93; N, 39.14; found: C,
50.28; H, 4.92; N, 39.13.
4.7.2 | (7aRS,11aSR)-methyl-
1,2,7a,8,11,11a-hexahydro-4H,7H-
2,2a1,3,6,6a,9,10,10a-octaazacyclopenta[6,7]
cycloocta[1,2,3,4-jkl]-as-indacen-4-one (8b)
4.7.5 | (8aRS,12aSR)-2,3,8a,9,12,12a-
hexahydro-8H-3,3a1,4,7,10,11,11a,13-octaaza-
6,7-ethenocyclopenta[5,6]cycloocta[1,2,3-de]
naphtalen-5(1H)-one (8e)
White solid, m.p. 292ꢀС to 294ꢀС; IR (KBr) νmax (cm−1):
1
1618 (C O stretching), 1591 (C N stretching); Н NMR
(400 MHz, DMSO-d6): δ 2.96 (s, 3Н, СН3), 3.63 to 3.66
(m, 1Н, СН), 3.83 to 3.87 (m, 1Н, СН), 3.97 to 4.10 (m,
3Н, 3СН), 4.19 to 4.23 (m, 1Н, СН), 4.27 to 4.33 (m, 1Н,
White solid, m.p. >300ꢀС; IR (KBr) νmax (cm−1): 2869
(CH stretching), 1622 (C O stretching), 1551 (C N

10
VASKEVYCH ET AL.
stretching); 1Н NMR (400 MHz, DMSO-d6): δ 1.99 to 2.02
(m, 1Н, СН), 2.07 to 2.17 (m, 2Н, СН2), 3.35 to 3.39 (m,
1Н, СН), 3.51 to 3.58 (m, 1Н, СН), 3.87 to 3.93 (m, 2Н,
2СН), 4.00 to 4.05 (m, 1Н, СН), 4.20 to 4.31 (m, 2Н, 2СН),
4.49 to 4.56 (m, 1Н, СН), 5.02 to 5.06 (m, 1Н, СН), 5.14 to
5.17 (m, 1Н, СН), 7.58 (s, 1Н, CН pyrazole), 8.33 to 8.36
(m, 1Н, NH); 13C NMR (150 MHz, DMSO-d6 + D2O): δ
20.3, 33.9, 50.8, 51.3, 53.6, 54.6, 68.1, 104.8, 135.3, 144.5,
151.7, 166.5; Anal. Calcd for C12H14N8О: C, 50.34; H,
4.93; N, 39.14; found: C, 50.29; H, 4.90; N, 39.10.
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5, 96.
4.8 | X-ray structure determination
4.8.1 | Crystal data for 8a
C11H12N8O, M = 272.29, monoclinic, space group C2/c,
а = 12.115(8), b = 11.244(8), c = 18.304(12)Å, β = 106.92
(2)ꢀ, V = 2385(3)Å3, Z = 8, dc = 1.516, μ 0.108 мм−1, F
(000) 1136, crystal size ca. 0.06 × 0.08 × 0.26 mm. All crys-
tallographic measurements were performed at 173 K on a
Bruker Smart Apex II diffractometer operating in the ω
scans mode. The intensity data were collected within the
[14] Winkley, M.V.; Diebold, J.L. Patent WO 1989008111, 1989.
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J. F. Bagli, J. Med. Chem. 1992, 35, 705.
θ
max ≤ 26.61ꢀ using Mo-Kα radiation (λ = 0.71078 Å). The
intensities of 16 153 reflections were collected (2496
unique reflections, Rmerg = 0.1279). The structure were
solved by direct methods and refined by the full-matrix
least-squares technique in the anisotropic approximation
for non-hydrogen atoms using the Bruker SHELXTL pro-
gram package.[32] All CH hydrogen atoms were placed at
calculated positions and refined as “riding” model and H
atom by the nitrogen atom were found from difference
Fourier synthesis and refined isotropically. Convergence
for 8a was obtained at R1 = 0.0557 and wR2 = 0.1026 for
1319 observed reflections with I ≥ 2σ(I); R1 = 0.1320 and
wR2 = 0.1284, GOF = 0.987 for 2496 independent reflec-
tions, 186 parameters, the largest and minimal peaks in
the final difference map 0.32 and −0.30 e/Å3.
Crystallographic data for the structure in this paper
have been deposited at Cambridge Crystallographic Data
Centre as supplementary publication numbers CCDC
1982420. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cam-
bridge CB21EZ, UK, (fax: +44-[0]1223-336 033 or e-mail:
deposit@ccdc.cam.ac.uk).
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ORCID
Ruslan I. Vaskevych https://orcid.org/0000-0001-9266-
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How to cite this article: Vaskevych RI,
Vaskevych AI, Rusanov EB, Mel'nyk OY,
Vovk MV. Synthesis of new-type 1,3,6-triazocine
via intramolecular reactions of iodocyclization and
[3+2] azido cycloaddition. J Heterocyclic Chem.
2020;1–11. https://doi.org/10.1002/jhet.4028
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SUPPORTING INFORMATION
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