Effect of the structural modification of 2-benzylamino-4-(4-iodophenyl) amino-6-methylpyrimidine on the biological activity of its derivatives

Article abstract of DOI:10.1134/S1070363212090198

Abstract-Modification of the aliphatic-aromatic moiety in the 2-benzylmino-4-(4-iodophenyl)amino-6- methylpyrimidine leads to a change in the site of biological action of the formed structural analogs. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070363212090198

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 9, pp. 1567–1572. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.V. Erkin, V.I. Krutikov, 2012, published in Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 9, pp. 1532–1537.
Effect of the Structural Modification
of 2-Benzylamino-4-(4-iodophenyl)amino-6-
methylpyrimidine on the Biological Activity
of Its Derivatives
A. V. Erkin and V. I. Krutikov
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: kruerk@yandex.ru
Received February 14, 2012
Abstract—Modification of the aliphatic-aromatic moiety in the 2-benzylmino-4-(4-iodophenyl)amino-6-
methylpyrimidine leads to a change in the site of biological action of the formed structural analogs.
DOI: 10.1134/S1070363212090198
To illustrate the importance of the presence of
aliphatic-aromatic fragments in the 2-benzylmino-4-(4-
of 6-methyl-2-methylthiopyrimidin-4(3H)-one (III)
with phenylamine and (furan-2-yl)methylamine,
exchange chlorination with phosphorus oxychloride of
the formed 2-amino-6-methylpyrimidin-4 (3H)-ones
(IVa, IVb), and finally the amination of the obtained
2-amino-6-methyl-4-chloropyrimidines (Va, Vb) with
4-iodophenylamine in the absence of a solvent at 90–
100ºC at 1:1 ratio of substrate and reagent. However,
we were confronted with a considerable tarring at the
exchange chloroination of compounds IVa and IVb. In
the case of aminopyrimidinone IVb we succeeded to
minimize this undesirable process by reducing the
iodophenyl)amino-6-methylpyrimidine
hydrochloride
molecule (I) for maintaining the capability to inhibit
the growth of Mycobacterium smegmatis cell culture at
low concentrations [1], we synthesized the hydro-
chlorides of 4-(4-iodophenyl)amino-6-methyl-2-phenyl-
aminopyrimidine (IIa), 4-(4-iodophenyl)amino-6-
methyl-2-[(furan-2-yl)methyl]aminopyrimidine (IIb),
and 2-amino-4-(4-iodophenyl)amino-6-methylpyrimi-
dine (IIc). Compounds IIa and IIb were prepared by
us along the unified scheme, which included amination
O
O
RNH2
HN
HN
R
N
N
Me
MeS
N
Me
H
IVа, IVb
III
POCl3
I
HN
Cl
N
I
NH2
N
N
R
R
N
N
Me
N
H
Me
H
IIа, IIb
Vа, Vb
R = Ph (a), (furan-2-yl)methyl (b)
1567

1568
ERKIN, KRUTIKOV
contact time of the substances, while such a change in
the conditions of synthesis of aminochloropyrimidine
Va did not result in a marked increase in its yield.
(water, ethanol), and sparingly soluble in non-polar
aprotic solvents (benzene, cyclohexane) even at
elevated temperature. The available data on the
solubility of chloropyrimidine VI in various solvents
[6] are not consistent with the above noted that points
to the discrepancy between the expected structure and
that of the isolated compound.
Structures of arylaminopyrimidines IIa, IIb are
1
confirmed by H NMR spectra, which contain the
characteristic signals of protons of the exocyclic amino
group at 10.4 (N2H), 11.0 (N4H), and 8.4 (N2H), 11.0
(N4H) ppm, respectively. Integral intensities of the
signals of aromatic protons correspond to their total
number.
High solubility of the isolated product in water
indicated the presence in its structure of the hydro-
philic fragment of phosphoric acid, whose appearance
might be due to O-phosphorylation of substrate VII
with the subsequent hydrolysis of intermediate (2-
amino-6-methylpyrimidin-4-yl)dichlorophosphate VIII.
Later on, we recorded the 1H and 31P NMR spectra and
got an opportunity to partially verify the correctness of
our assumptions and to formulate a conclusion on the
preferential direction of the reaction course in the of
exchange chlorination of compound VII. The 1H NMR
spectrum contains as singlets the paired signals of the
protons of the methyl and methine groups near 2.2 and
2.4 ppm and about 5.7 and 6.9 ppm, respectively. The
31P NMR spectrum contains the signals of phosphorus
nuclei with chemical shifts –0.5 and –12.6 ppm
attributable to monosubstituted phosphoric acid and its
amide [7], respectively. Less shielded singlets of
protons occupied the position close to the signals
characteristic of the protons of methyl groups and
connected with the C5 atom in various 2-amino-6-
methylpyrimidin-4(3H)-ones, the positions of signals
more downfield were close to those of analogs protons
in 2-amino-6-methyl-4-chloropyrimidines [1, 8]. These
spectral characteristics should be interpreted as
corresponding to a mixture of (2-amino-6-methyl-
pyrimidin-4-yl)phosphoric acid (IX) and phosphoric
According to literature data, compound IIc can be
obtained by amination of 2-amino-6-methyl-4-chloro-
pyrimidine (VI) with 4-iodophenylamine [2], and
substrate VI, by exchange chlorination of 2-amino-6-
methylpyrimidin-4(3H)-one (VII) with phosphorus
oxychloride either without a solvent [3], or in 1,2-
dichlorobenzene [4], or with a mixture of phosphorus
oxychloride and pentachloride [5]. While carrying out
the exchange chlorination of pyrimidinone VII we
noted that the procedures described in the cited papers
are irreproducible. Refluxing compound VII with an
excess of phosphorus oxychloride until the end of the
release of hydrogen chloride followed by the treatment
of the reaction mixture with ice and alkalinizing it with
25% aqueous ammonia solution to pH ~ 8–9 (method
a) leads to the formation of small amounts of a mixture
of substances inseparable by fractional crystallization.
The same result was achieved by performing the
reaction in 1,2-dichlorobenzene. Heating pyrimidi-
none VII with a mixture of phosphorus oxychloride
and pentachloride followed by processing the reaction
mixture along the method a we obtained a solution from
which after some time a colorless precipitate separated,
which was readily soluble in polar protic solvents
Cl
Cl
O
P
Cl
N
O
O
Cl
P
N
HN
H2N
N
PCl5 + POCl3
+
O
Cl
N
Me
N
Me
H2N
N
Me
H
XI
VIII
VII
OH
HO
O
P
Cl
O
OH
H2O
N
N
+
+
VIII XI
P
O
N
N
Me
H2N
N
Me
HO
H
IX
X
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 9 2012

EFFECT OF THE STRUCTURAL MODIFICATION
1569
N-(6-methyl-4-chloropyrimidin-2-yl)amide (X) formed
at the hydrolysis of the dichlorophosphate VIII and N-
(6-methyl-4-chloropyrimidin-2-yl)dichlorophosphor-
amide XI, the primary compounds arising in the
reaction of pyrimidinone VII with a mixture of
phosphorus oxychloride and pentachloride.
formic acid and thus prepared 6-methyl-2-formylaminopyri-
midin-4(3H)-one XII, which at the treatment with
phosphorus oxychloride was converted to 6-methyl-2-
formylamino-4-chloropyrimidine (XIII), free from (6-
methyl-2-formylaminopyrimidin-4-yl)phosphoric acid
1
as a potential impurity. The H NMR spectrum of the
formylaminochloropyrimidine XIII is characterized by
the presence of singlets of protons at the C5 at 6.4 ppm
and secondary amino group at about 6.8 ppm, shifted
downfield as compared with the signals of the same
groups in the parent compound XII due to the
electron-withdrawing effect of halogen substituent, and
by the absence of the proton signal of the cyclic amino
group, existing in the region of 10.7 ppm in the
spectrum of formylaminopyrimidinone XII.
The ratio of integral intensities of proton signals of
methyl or methine groups in compounds IX and X is
5:1 suggesting a prevalence of O-phosphorylation over
the replacement of the oxygen atom by chlorine in the
pyrimidinone VII.
In order to influence the reactivity of the compound
VII we performed formylation of the substrate with
O
Cl
HN
POCl3
N
HCOOH
VII
N
N
Me
N
N
Me
O
O
H
H
XII
XIII
In contrast to the IR spectrum of compound XII
containing superimposed band of stretching vibrations
of C=O groups located near 1660 cm–1 the absorption
band of the carbonyl group of formylaminochloropyri-
midine XIII appears in the region of the stretching
vibrations of carbonyl groups of secondary amides
(1647 cm–1). The displacement of the band “amide-II”
of this compound to higher frequencies (1548 cm–1)
compared with a similar band in the spectrum of
formylaminopyrimidinone XII (1498 cm–1) points to
the disappearance of the potential intramolecular
hydrogen bond in the substrate molecule.
Finally, the appearance in the spectrum of
compound XIII of the absorption band near 1475 cm–1
confirms aromatic character of this substance.
The assumed scheme of the formation of an
intramolecular hydrogen bond was illustrated by
comparing the intensities of the coincident frequencies
of stretching vibrations of C=O groups of formyl-
aminopyrimidinone XII and its precursor VII
(1660 cm–1), whose ratio was 2.5:1.
The condensation of formylaminochloropyrimidine
XIII with 4-iodophenylamine taken in equimolar ratio
in the absence of solvent at 100ºC resulted in 4-(4-
iodophenyl)amino-6-methyl-2-formylaminopyrimidine
hydrochloride (XIV). This compound was subjected to
deformylation by heating with concentrated hydro-
chloric acid at 80–90°C to give diaminopyrimidine
IIc .
O
O
H
N
H
O
N
O
N
N
H
N
Me
N
H
Me
I
I
H2N
I
HCl
HN
HN
XIII
N
N
H2N
N
IIc
I
Me
O
N
N
Me
H
XIV
H2N
IX + X
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 9 2012

1570
ERKIN, KRUTIKOV
We isolated the same compound IIc at the
individuality of the compounds was monitored by TLC
on the Silufol UV-254 plates in the systems: 1-
butanol–acetic acid–water 1:1:1 (A), tetrachloro-
metane–2-propanol, 4:1 (B), acetone–hexane, 1:1 (C),
acetone–heptane, 1:1 (D) tetrachlorometane–2-pro-
panol, 5:1 (E). The spots were developed by UV light.
Elemental analysis was performed on a Hewlett
Packard B-185 analyzer. Aqueous or aqueous-ethanol
solutions of compounds IIa–IIc and XIV gave a
positive test for the presence of chloride ion with an
aqueous solution of silver nitrate. 6-Methyl-2-
methylthiopyrimidin-4(3H)-one III was prepared by
the method [9], 2-amino-6-methylpyrimidin-4(3H)-one
VII, according to [10]. A modification of the method
[11] for the synthesis of 4-iodophenylamine consisting
in an additional extraction of the product with
hexane allowed us to prepare this amine as colorless
needles in 59% yield, mp 64ºC (published [12]: mp
63–65ºC).
amination of a mixture of pyrimidylphosphoric acid IX
and phosphoric chloropyrimidylamide X with 4-
iodophenylamine in the absence of solvent at 100ºC,
with subsequent processing of the reaction product
with concentrated hydrochloric acid (method b).
Due to the high expenditure of the solvent at the
recrystallization of the formamide XIV, we subse-
quently restricted ourselves to a thorough washing the
substrate prior to introduction into the deformylation
reaction and thus increased the total yield of compound
IIc from 10 to 50% calculated on the original
formylaminochloropyrimidine XIII (method c).
It should be noted that in order to prevent
contamination of compound XIV with tarry substances
of unknown nature it is necessary to control strictly the
conditions of interaction of formylaminochloro-
pyrimidine XIII with 4-iodophenylamine and to keep
the process temperature no higher than it is specified.
4-(4-Iodophenyl)amino-6-methyl-2-phenylamino-
pyrimidine (IIa). A mixture of 80 mg of phenyl-
aminochloropyrimidine VIa and 80 mg of 4-iodo-
phenylamine was kept at 95ºC to solidification. The
crushed solid was crystallized from ethanol–DMF
(10:1), washed with ethanol, and after drying at 60ºC
for 4 h 51 mg (32%) of compound IIa was isolated as
1
While the H NMR spectrum of formamide XIV
differs from the spectrum of compound XIII by the
presence of singlets of aromatic protons and protons at
the atom N4 in the region of 7.6 and 10.8 ppm
respectively, the spectrum of diaminopyrimidine IIc
practically coincides with the spectrum of compound
XIV with the exception of the region of 7.5–8.0 ppm,
where the proton signals of primary amino group and
aromatic protons form a pseudo-singlet with an
integral intensity corresponding to six protons.
1
hydrochloride, mp 285ºC (dec.), Rf 0.82 (A). H NMR
spectrum, δ, ppm: 2.38 s (3H, Me), 6.34 s (1H, CH),
7.19–7.60 m (9H, Ar), 10.37 s (1H, NH), 10.92 s (1H,
NH), 13.24 br.s (1H, N+H). Found, %: C 46.13, H
3.52, N 12.46. C17H15IN4O·HCl. Calculated, %: C
46.54, H 3.68, N 12.77.
The removal of the methylene group or the benzyl
fragment from the structure of benzylaminopyrimidine
I resulted in a significant change in the biological
action of respective compounds IIa and IIc, which
acquired the ability to inhibit the cell growth of the
related culture, Mycobacterium tuberculosis, in
concentrations of 0.05 and 0.0125 g l–1, respectively.
The replacement of the aromatic ring of benzylamino-
pyrimidine I by a heterocycle led to a loss of the anti-
mycobacterial activity by the furylaminopyrimidine
IIb at the concentrations up to 0.1 g l–1.
4-(4-Iodophenyl)amino-6-methyl-2-[(furan-2-yl)-
methyl]aminopyrimidine (IIb). A mixture of 0.4 g of
furfurylaminochloropyrimidine VIb and 0.39 g of 4-
iodophenylamine was heated to 95ºC, kept at this
temperature till the turbidity of the melt, and then at
110–115ºC till hardening. The crushed solid was
crystallized from ethanol. After drying at 60ºC for 4 h
we obtained 0.57 g (72%) of compound IIb as
hydrochloride, mp 267ºC, Rf 0.80 (A). 1H NMR
spectrum, δ, ppm: 2.31 s (3H, Me), 4.58 s (2H, CH2),
6.29 m (3H, Ar), 7.62 m (5H, Ar), 8.43 s (1H, NH) ,
11.08 s (1H, NH), 13.34 br.s (1H, N+H). Found, %: C
43.07, H 3.41, N 12.21. C16H15IN4O·HCl. Calculated,
%: C 43.41, H 3.64, N 12.66.
EXPERIMENTAL
1H and 31P NMR spectra were recorded on a Bruker
WM-400 (operating frequency 400.13 MHz) and a
Bruker AC-200 (operating frequency 81.01 MHz)
spectrometers, respectively, solvent DMSO-d6, as
internal reference were utilized the residual proton
signals of the solvent. IR spectra were obtained on a
FTIR FSM-1201 spectrometer from KBr tablets. The
2-Amino-4-(4-iodophenyl)amino-6-methylpyr-
imidine (IIc). a. A mixture of 0.6 g of formyl-
aminopyrimidine XIV and 10 ml of concentrated
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 9 2012

EFFECT OF THE STRUCTURAL MODIFICATION
1571
hydrochloric acid was heated at 85–90°C for 30 min,
then the suspension was cooled, filtered, and the
filtrate evaporated in vacuo to dryness. The combined
residue was recrystallized from water and dried at
60ºC for 6 h. 0.28 g (51%) of compound IIc was
isolated as hydrochloride, mp 294ºC (decomp.), Rf
0.76 (A). 1H NMR spectrum, δ, ppm: 2.29 s (3H, Me),
6.27 s (1H, CH), 7.63 s (6H, NH2, Ar), 10.90 s (1H,
NH), 13.13 s (1H, N+H). Found, %: C 35.92, H 3.13, N
15.09. C11H11IN4·HCl. Calculated, %: C 36.44, H 3.34,
N 15.45.
was heated to 150ºC and maintained at this tempera-
ture until complete release of methanethiol. After
distilling off the excess (furan-2-yl)methylamine in a
vacuum the oily residue formed was crystallized by
trituration with 30 ml of acetonitrile, the precipitate
was filtered off, recrystallized from acetonitrile and
after drying at 60ºC for 4 h 4.60 g (75%) of compound
1
IVb was isolated, mp 159ºC, Rf 0.25 (B). H NMR
spectrum, δ, ppm: 2.04 s (3H, Me), 4.46 s (2H, CH2),
5.38 s (1H, CH), 6.25, 6.34 m (2H, Ht), 6.65 s (1H,
NHe), 7.49 d (1H, Ht), 10.41 s (1H, NH). Found, %: C
58.17, H 5.64, N 20.12. C10H11N3O2. Calculated, %: C
58.53, H 5.40, N 20.48.
b. 0.2 g of a mixture of acids IX and X and 0.21 g
of 4-iodophenylamine was heated at 90°C to
solidification. The solid was crushed and suspended in
5 ml of concentrated hydrochloric acid, the precipitate
was filtered off, washed with a small amount of cold
water, and recrystallized from 2-propanol with the
addition of DMF to create a homogenous solution.
After washing with 2-propanol, the product was dried
at 60ºC for 6 h. 67 mg (20%, calculated on 4-
iodophenylamine) of compound IIc was isolated as
hydrochloride.
6-Methyl-2-phenylamino-4-chloropyrimidine (Va).
A mixture of 0.6 g of phenylaminopyrimidinone IVa
and 25 g of freshly distilled phosphorus oxychloride
was refluxed for 10 min. The phosphorus oxychloride
excess was distilled off in vacuo, the residue was
mixed with a thoroughly crushed ice and alkalinized
with 25% aqueous ammonia to pH 9. The aqueous
layer was decanted, the oily residue was crystallized
by adding 50% aqueous ethanol. The resulting
precipitate was filtered off and recrystallized from a
mixture of the same solvent and washed with water.
After drying in a vacuum over phosphorus pentoxide
90 mg (13%) of compound Va was isolated, mp 89ºC,
c. A mixture of 1 g of formylaminochloro-
pyrimidine XIII and 1.27 g of 4-iodophenylamine was
heated at 100ºC till solidification. The reaction product
was crushed and heated in 30 ml of concentrated
hydrochloric acid at 85–90°C for 30 min, then cooled,
the precipitate was filtered off, and the filtrate was
evaporated in vacuo to dryness. The combined residue
was recrystallized from water and dried at 60ºC. We
obtained 0.93 g (51%, calculated on the original
formylaminochloropyrimidine) of compound IIc as
hydrochloride.
1
Rf 0.53 (D). H NMR spectrum, δ, ppm: 2.37 s (3H,
Me), 6.76 s (1H, CH), 6.92–6.72 m (5H, Ph), 9.85 s
(1H, NH). Found, %: C 59.76, H 4.77, N 18.96.
C11H10ClN3. Calculated, %: C 60.14, H 4.59, N 19.13.
6-Methyl-2-[(furan-2-yl)methyl]amino-4-chloro-
pyrimidine (Vb). A mixture of 2 g of furfuryl-
aminopyrimidinone IVb and 25 g of freshly distilled
phosphorus oxychloride was refluxed for 20 min. After
distilling off the excess phosphorus oxychloride in a
vacuum, the residual oil was mixed with finely crushed
ice, alkalinized with 25% aqueous ammonia solution to
pH 9–10, and triturated to obtain a suspension. The
precipitate was filtered off, washed with water, and
recrystallized twice from 50% aqueous ethanol with
decanting the solvent from the insoluble oily residue.
After drying in a vacuum over phosphorus pentoxide
0.79 g (36%) of compound Vb was obtained, mp 94ºC,
6-Methyl-2-phenylaminopyrimidin-4(3H)-one
(IVa). A mixture of 1.56 g of thioester III and 0.93 g
of freshly distilled phenylamine was heated to 160ºC
and maintained at this temperature until complete
release of methanethiol. The cooled solid was crushed
and recrystallized from 60% aqueous acetic acid. After
washing with water and drying at 60ºC for 6 h 0.66 g
(33%) of compound IVa was isolated, mp 252ºC, Rf
0.69 (B). 1H NMR spectrum, δ, ppm: 2.13 s (3H, Me),
5.63 s (1H, CH), 6.96–7.62 s (5H, Ph), 8.70 br.s (1H,
NHe), 10.52 br.s (1H, NH). Found, %: C 65.13, H
5.12, N 20.89. C11H11N3O. Calculated, %: C 65.66, H
5.51, N 20.88.
1
Rf 0.75 (D). H NMR spectrum, δ, ppm: 2.26 s (3H,
Me), 4.45, 4.46 d (2H, CH2), 6.19–6.49 m (3H, Ar),
7.42 s (1H, Ar), 7.77 br.s (1H, NH). Found, %: C
53.21%, H 4.39, N 18.56. C10H10ClN3O. Calculated,
%: C 53.70%, H 4.51, N 18.79. When the time of
contact of the reagents was increased to 1 h the yield
of the compound Vb decreased to 0.17 g (7.6%).
6-Methyl-2-[(furan-2-yl)methyl]aminopyrimidin-
4(3H)-one (IVb). A mixture of 4.68 g of thioester III
and 5.82 g of freshly distilled (furan-2-yl)methylamine
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 9 2012

1572
ERKIN, KRUTIKOV
1
6-Methyl-2-formylaminopyrimidin-4(3H)-one
292ºC (decomp.), Rf 0.89 (A). H NMR spectrum, δ,
ppm: 2.29 s (3H, Me), 6.25 s (1H, CH), 7.62 s (4H,
Ar), 8.09 br.s (2H, NHe, CHO), 10.85 s (1H, N4H),
13.12 br.s (1H, N+H). Found, %: C 36.45%, H 2.84, N
14.05. C12H11IN4O·HCl. Calculated, %: C 36.90%, H
3.10, N 14.34.
(XII). A mixture of 6.36 g pyrimidinone VII and
90 ml of formic acid was refluxed for 8 h. After the
complete removal of excess acid in vacuo, the residue
was refluxed with 40 ml of ethanol for 30 min, on
cooling the precipitate was filtered off, washed with
ethanol, and dried at 60ºC for 6 h. 6.95 g (89%) of
compound XII was isolated, mp > 300ºC, Rf 0.59 (A).
To obtain an analytical sample, the product was
recrystallized from ethanol–DMF (4:1), washed with
ethanol, and dried in a vacuum over phosphorus
ACKNOWLEDGMENTS
The authors express their deep gratitude to I.V.
Klaptyuk, St. Petersburg division of the Research
Institute for Fire Protection, for recording the IR
spectra, as well as Proffesor Tets and coworkers (St.
Petersburg Pavlov State Medical University) for
microbiological studies.
1
pentoxide. H NMR spectrum, δ, ppm: 1.98 s (3H,
Me), 5.36 s (1H, CH), 6.51 br.s (2H, NHe, CHO),
10.69 br.s (1H, NH). Found, %: C 46.51%, H 4.35, N
27.73. C6H7N3O2. Calculated, %: C 47.06%, H 4.61, N
27.44.
REFERENCES
1. Erkin, A.V., Krutikov, V.I., and Smirnova, E.B., Zh.
Obshch. Khim., 2008, vol. 78, no. 10, p. 1708.
2. O’Brien, D.E., Baiocchi, F., Robins, R.K., and Cheng, C.C.,
J. Org. Chem., 1962, vol. 27, no. 3, p. 1104.
3. Gabriel, S. and Colman, J., Ber., 1899, vol. 32, no. 3,
6-Methyl-2-formylamino-4-chloropyrimidine
(XIII). A mixture of 6.95 g of formylaminopyrimidi-
none XII and 60 ml of freshly distilled phosphorus
oxychloride was refluxed for 1.5 h. The excess phos-
phorus oxychloride was completely removed in vacuo,
the residue was mixed with finely crushed ice and
neutralized with 25% aqueous ammonia. The suspen-
sion was left at room temperature for three days, the
precipitate was filtered off, washed with a small
amount of cold water, and dried in a stream of warm
air to constant weight. The dry product was extracted
with benzene in a Soxlet apparatus, and the precipitate
separated from the extract was dried at 60ºC for
6 h. 3.33 g (43%) of compound XIII was obtained, mp
184ºC, Rf 0.82 (A). 1H NMR spectrum, δ, ppm:
2.22 s (3H, Me), 6.45 s (1H, CH), 6.84 s (2H, NHe,
CHO). Found, %: C 41.76%, H 3.60, N 24.39.
C6H6ClN3O. Calculated, %: C 42.00%, H 3.52, N
24.49.
p. 2921.
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2011, vol. 81, no. 8. S. 1354.
4-(4-Iodophenyl)amino-6-methyl-2-formylamino-
pyrimidine (XIV). A mixture of 0.5 g formylamino-
chloropyrimidine XIII and 0.64 g of 4-iodophenyl-
amine was heated at 100ºC to solidification. The solid
was crushed and recrystallized from ethanol, washed
with ethanol, and dried at 60ºC for 4 h to obtain 0.6 g
(52%) of compound XIV as the hydrochloride, mp
11. Busev, A.I., Sintez novykh organicheskikh reagentov
dlya neorganicheskogo analiza (Synthesis of New
Organic Chemicals for Inorganic Analysis), Moscow:
Mosk. Gos. Univ., 1972.
12. Svoistva organicheskikh soedinenii. Spravochnik
(Properties of Organic Compounds. Handbook),
Potekhin, A.A., Ed., Leningrad: Khimiya, 1984.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 9 2012