Synthesis of new purine, pteridine, and other pyrimidine derivatives

Article abstract of DOI:10.1134/S1070428007030219

The reaction of malononitrile dimer with phenyl isothiocyanate gave (6-amino-1-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-ylidene)malononitrile which was then used as starting material in the synthesis of pharmacologically important fused pyrimidine de

Full text of DOI:10.1134/S1070428007030219

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 3, pp. 443–448. © Pleiades Publishing, Ltd., 2007.
Published in Russian in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 3, pp. 443–449.
Synthesis of New Purine, Pteridine, and Other
Pyrimidine Derivatives*
E. Abdel-Latif, H. M. Mustafa, H. A. Etman, and A. A. Fadda
University of Mansoura, Faculty of Science, Chemistry Department, Mansoura 35516, Egypt
e-mail: ehabattia00@gmx.net
Received December 26, 2005
Abstract—The reaction of malononitrile dimer with phenyl isothiocyanate gave (6-amino-1-phenyl-2-thioxo-
1,2,3,4-tetrahydropyrimidin-4-ylidene)malononitrile which was then used as starting material in the synthesis
of pharmacologically important fused pyrimidine derivatives, such as 4-dicyanomethylidene-1,5-diphenyl-2-
thioxo-1,2,3,4-tetrahydropyrrolo[2,3-d]pyrimidine, 6-cyano-4-dicyanomethylidene-7-methylsulfanyl-5-oxo-1-
phenyl-2-thioxo-1,2,3,4,5,8-hexahydropyrido[2,3-d]pyrimidine, 6-dicyanomethylidene-3-phenyl-2-thioxo-
1,2,3,6-tetrahydro-9H-purine, and 6-substituted 4-dicyanomethylidene-7-oxo-1-phenyl-2-thioxo-1,2,3,4,7,8-
hexahydropteridines.
DOI: 10.1134/S1070428007030219
(deaza analogs of pteridines) and their oxo derivatives
also attract interest as potential biologically active sub-
stances [8]. Taking into account the above stated, in the
present article we report on the synthesis of new func-
tionally substituted fused pyrimidine derivatives on the
basis of 2-(6-amino-1-phenyl-2-thioxo-1,2,3,4-tetra-
hydropyrimidin-4-ylidene)malononitrile (II).
We recently studied reactions of phenyl isocyanate
with compounds having an activated methylene group
[9, 10]. 6-Aminopyrimidine II was synthesized by
reaction of phenyl isothiocyanate with malononitrile
Pyrimidine is the parent heteroring of a very
important group of compounds that are extensively
studied due to their occurrence in living systems.
Compounds containing a pyrimidine ring have been
reported as antibacterial and antifungal agents, as well
as those exhibiting anti-HIV activity [1–4]. Substituted
aminopyrimidine fragments are present in molecules of
marketed drugs, such as antiatherosclerotic Aronixil,
antihistaminic Thonzylamine, antianxiolytic Bus-
pirone, antipsoriatic Enazadrem, and other medicinally
relevant compounds [5–7]. Pyrido[2,3-d]pyrimidines
Scheme 1.
NC
CN
NC
HN
CN
H2N
NC
CN
CN
N
Ar
PhNCS, pyridine, Δ
Ar2N+ Cl–
HN
N
S
N
NH2
S
N
NH2
Ph
II
Ph
I
IIIa–IIIc
H2N
NC
CN
Ar2N+ Cl–
PhNCS, pyridine, Δ
I
CN
NH
Ar
IIIa–IIIc
N
IVa–IVc
III, IV, Ar = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c).
* The text was submitted by the authors in English.
443

ABDEL-LATIF et al.
444
Scheme 2.
II
PhCO
Br
MeS
MeS
CN
C
NNHPh
C
C
PhCOCH2Br
Ac2O
CN
COOEt
VIII
NC
CN
Ph
NC
HN
CN
NC
NC
HN
CN
O
Ph
CN
N
Ph
HN
HN
N
N
H
N
S
N
S
N
S
N
NHAc
S
N
N
H
SMe
H
Ph
Ph
Ph
Ph
V
VI
VII
IX
dimer (I, 2-aminoprop-1-ene-1,1,3-tricarbonitrile) [11]
in boiling pyridine (Scheme 1). The reaction gave the
only product whose elemental composition corre-
sponded to the formula C13H8N5S. It was identified as
6-amino-4-dicyanomethyliden-1-phenyl-2-thioxo-
1,2,3,4-tetrahydropyrimidine (II) on the basis of the
IR, 1H NMR, and mass spectra. The IR spectrum of II
contained strong absorption bands in the region 3466–
3333 cm–1 due to stretching vibrations of the NH2 and
NH groups, and the band at 2195 cm–1 was assigned to
mide in boiling ethanol in the presence of a catalytic
amount of triethylamine gave pyrrolopyrimidine deriv-
ative V (Scheme 2). The formation of pyrrole ring is
the result of alkylation of the amino group, followed
by intramolecular heterocyclization involving the C5
atom in the pyrimidine ring and the carbonyl group in
the substituent at the amino group [17]. The structure
of compound V was assigned on the basis of its
elemental composition and spectral data. The IR
spectrum of V contained absorption bands at 3300 and
3180 cm–1, belonging to stretching vibrations of
the two NH groups, and cyano group absorption at
2200 cm–1. The pyrrole CH proton signal appeared in
1
the cyano groups. In the H NMR spectrum of II we
observed a singlet at δ 6.80 ppm, which corresponds to
proton on C5 in the pyrimidine ring; protons of the aro-
matic ring and NH group gave a multiplet at δ 7.05–
7.40 ppm; and protons of the amino group resonated as
a broadened singlet at δ 8.60 ppm.
1
the H NMR spectrum of V at δ 5.6 ppm, aromatic
multiplet was located in the region δ 7.1–7.8 ppm, and
two broadened singlets from the NH protons (D2O-
exchangeable) were present at δ 8.3 and 9.2 ppm. We
failed to synthesize phenyldiazenylpyrrolo[2,3-d]pyri-
midine VI by reaction of II with 2-bromo-1-phenyl-2-
phenylhydrazonoethan-1-one.
By diazo coupling of 6-aminopyrimidine II with
aromatic diazonium salts we obtained the correspond-
ing 5-aryldiazenyl derivatives IIIa–IIIc (Scheme 1)
whose structure was confirmed by spectral data and
independent syntheses from phenyl isothiocyanate and
arylazo derivative IV of malononitrile dimer in boiling
pyridine. Compound IIIa displayed in the IR spectrum
absorption bands at 3394–3236 (NH2, NH) and
2229 cm–1 (C≡N). The 1H NMR spectrum of IIIc con-
tained a singlet at δ 3.80 ppm (CH3O), multiplet in the
region δ 7.05–7.65 ppm due to aromatic protons, and
downfield singlets at δ 9.20 (NH) and 11.45 ppm
(NH2). In the mass spectrum of IIIb we observed the
molecular ion peak with m/z 385 (C20H15N7S).
Treatment of 6-aminopyrimidine II with acetic
anhydride gave acetylaminopyrimidine VII which
showed in the IR spectrum absorption bands at 3205,
2200, and 1676 cm–1 corresponding to stretching vibra-
tions of the NH and CN groups and amide carbonyl,
respectively. The molecular ion peak ([M]+, m/z 309)
in the mass spectrum of VII had a relative intensity
of 35%, while the base peak was that with m/z 266
[M – COCH3]+ (100%).
Fused pyridopyrimidine IX was synthesized by
reaction of compound II with ethyl 2-cyano-2,3-bis-
(methylsulfanyl)prop-2-enoate (VIII) [18] in boiling
dimethylformamide containing a catalytic amount of
triethylamine (Scheme 2). The structure of IX was
confirmed by the spectral and analytical data. Stretch-
Many fused heterocyclic systems, especially those
including a pyrimidine ring, exhibit analgesic, antihy-
pertensive, and antiinflammatory activity and are used
as herbicides and plant growth regulators [12–16]. The
reaction of 6-aminopyrimidine II with phenacyl bro-
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SYNTHESIS OF NEW PURINE, PTERIDINE, AND OTHER PYRIMIDINE DERIVATIVES
445
Scheme 3.
NC
HN
CN
NC
HN
CN
(1) Na2S2O4
(2) HCl
NO
NH2
NH2
NaNO2, aq. AcOH
II
·HCl
S
N
NH2
S
N
Ph
Ph
X
XI
NC
CN
NC
HN
CN
NH2
CHO
N
HN
HCOOH
N
H
S
N
N
S
N
H
Ph
Ph
XII
ing vibrations of the NH groups gave rise to an absorp-
tion band at 3330 cm–1 in the IR spectrum; and bands
at 2216 and 1700 cm–1 were assigned to vibrations of
the C≡N and C=O groups, respectively. Protons of the
No absorption bands assignable to amino groups were
present in the IR spectrum of XII, and its H NMR
spectrum contained a singlet at δ 8.05 ppm due to CH
proton in the imidazole ring.
1
1
methylsulfanyl groups resonated in the H NMR spec-
Pteridine derivatives are used in a variety of fields,
e.g., as drugs in pharmaceutics [22] and base com-
ponents of several nucleosides in biology [23]; other
biological activities of pteridine derivatives were also
reported [24]. We synthesized pteridines XIIIa and
XIIIb by heating 5-nitrosopyrimidine X with ethyl
acetoacetate and diethyl malonate, respectively, in the
presence of sodium ethoxide (Scheme 4). The structure
of XIIIa and XIIIb was determined on the basis of
their analytical and spectral data.
trum as a singlet at δ 2.60 ppm, the NH signals were
located at δ 8.4 and 9.6 ppm (D2O-exchangeable),
and aromatic protons gave a multiplet in the region
δ 7.2–8.0 ppm.
Two main synthetic approaches to the fused purine
system are known. The first of these includes synthesis
of an imidazole derivative, followed by pyrimidine
ring closure. The second route (which was used in
the present work) implies initial synthesis of a 5,6-di-
aminopyrimidine derivative [19, 20] which is then
brought into condensation with an appropriate one-
carbon component to close the second (pyrrole) ring.
Our interest in purine derivatives originates from the
facts that such purine derivatives as theophylline,
caffeine, and theobromine are widely distributed in the
nature and that they exhibit versatile biological activity
[21]. Compound II was converted into purine deriva-
tive XII in three steps. In the first step, 6-aminopyri-
midine II was subjected to nitrosation with sodium
nitrite in acetic acid; in the IR spectrum of 5-nitroso
compound X thus formed we observed absorption
bands at 3420–3280 (NH2), 3220 (NH), and 2220 cm–1
Scheme 4.
NC
HN
CN
O
O
O
O
N
EtONa/EtOH
X
+
Y
Y
OEt
S
N
N
H
Ph
XIIIa, XIIIb
XIII, Y = Me (a), EtO (b).
EXPERIMENTAL
1
(CN), while its H NMR spectrum lacked singlet at
δ 6.80 ppm corresponding to 5-H in the initial pyrimi-
dine. The second step was reduction of nitroso com-
pound X with sodium dithionite to obtain daminopyri-
midine XI. Heating of the latter in boiling formic acid
afforded the target 6-dicyanomethylidene-3-phenyl-2-
thioxo-1,2,3,6-tetrahydro-9H-purine (XII) (Scheme 3).
The melting points were determined on an Electro-
thermal Gallenkamp melting point apparatus and were
not corrected. The IR spectra were recorded in KBr on
1
a Mattson 5000 FTIR spectrometer. The H NMR
spectra were measured from solutions in CDCl3 or
DMSO-d6 on a Bruker WP 300 instrument using tetra-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 3 2007

ABDEL-LATIF et al.
446
1
methylsilane as internal reference. The mass spectra
(electron impact, 70 eV) were run on a Finnigan MAT
212 mass spectrometer. The elemental analyses were
obtained at the microanalytical unit, Faculty of
Science, University of Mansoura, Egypt.
(CN); 1627 (C=C); 1549 (N=N). H NMR spectrum
(DMSO-d6), δ, ppm: 7.10–7.60 m (10H, Harom), 9.35 s
(1H, NH), 10.80 s (2H, NH2). Mass spectrum, m/z
(Irel, %): 371 [M]+ (35). Found, %: C 61.62; H 3.67;
N 26.28. C19H13N7S. Calculated, %: C 61.44; H 3.53;
N 26.40. M 371.42.
(6-Amino-1-phenyl-2-thioxo-1,2,3,4-tetrahydro-
pyrimidin-4-ylidene)malononitrile (II). Phenyl iso-
thiocyanate, 0.01 mol, was added to a solution of
0.01 mol of malononitrile dimer I in 30 ml of anhy-
drous pyridine. The mixture was heated for 2 h under
reflux, allowed to cool down to room temperature,
poured into ice water, and neutralized with dilute
hydrochloric acid for complete precipitation. The pre-
cipitate was filtered off, washed with water, and re-
crystallized from ethanol. Yield 72%, green crystals,
mp 225°C. IR spectrum, ν, cm–1: 3466, 3381, 3333
(NH2, NH); 2195 (CN). 1H NMR spectrum (DMSO-d6),
[6-Amino-1-phenyl-2-thioxo-5-(p-tolyldiazenyl)-
1,2,3,4-tetrahydropyrimidin-4-ylidene]malononi-
trile (IIIb). Yield 73%, red crystals, mp 268°C. IR
spectrum, ν, cm–1: 3398, 3305, 3276 (NH2, NH); 2228
1
(CN); 1624 (C=C); 1558 (N=N). H NMR spectrum
(DMSO-d6), δ, ppm: 2.40 s (3H, CH3), 7.00–7.50 m
(9H, Harom), 9.10 s (1H, NH), 11.20 s (2H, NH2). Mass
spectrum, m/z (Irel, %): 385 [M]+ (20). Found, %:
C 62.47; H 3.73; N 25.58. C20H15N7S. Calculated, %:
C 62.32; H 3.92; N 25.44. M 385.44.
[6-Amino-5-(p-methoxyphenyldiazenyl)-1-phen-
yl-2-thioxo-1,2,3,4-tetrahydropyrimidin-4-ylidene]-
malononitrile (IIIc). Yield 78%, red crystals,
mp 280°C. IR spectrum, ν, cm–1: 3438, 3324, 3244
(NH2, NH); 2237 (CN); 1625 (C=C); 1549 (N=N).
1H NMR spectrum (DMSO-d6), δ, ppm: 3.80 s (3H,
OCH3), 7.05–7.65 m (9H, Harom), 9.20 s (1H, NH),
11.45 s (2H, NH2). Found, %: C 59.91; H 3.82;
N 24.49. C20H15N7OS. Calculated, %: C 59.84; H 3.77;
N 24.42. M 401.44.
δ, ppm: 6.80 s (1H, 5-H), 7.05–7.40 m (6H, Harom
,
NH), 8.60 br.s (2H, NH2). Mass spectrum, m/z (Irel, %):
267 [M]+ (100). Found, %: C 58.37; H 3.44; N 26.26.
C13H9N5S. Calculated, %: C 58.41; H 3.39; N.20.
M 267.31.
[5-(Aryldiazenyl)-6-amino-1-phenyl-2-thioxo-
1,2,3,4-tetrahydropyrimidin-4-ylidene]malono-
nitriles IIIa–IIIc (general procedure). a. A solution of
0.01 mol of compound II in 50 ml of ethanol con-
taining 4.0 g of sodium acetate was cooled to 0°C, and
a cold solution of 0.01 mol of the corresponding arene-
diazonium chloride (prepared by addition of a cold
solution of 0.7 g of sodium nitrite in 10 ml of water to
a cold suspension of 0.01 mol of the corresponding
aromatic amine in 3 ml of concentrated hydrochloric
acid under stirring) was added under continuous stir-
ring. The mixture was stirred for 2 h at 0–5°C and
diluted with water, and the precipitate was filtered off,
dried, and recrystallized from ethanol–DMF (3:1).
(1,5-Diphenyl-2-thioxo-1,2,3,4-tetrahydropyr-
rolo[2,3-d]pyrimidin-4-ylidene)malononitrile (V).
A mixture of 0.005 mol of compound II, 0.005 mol of
phenacyl bromide, and 4 drops of triethylamine in
30 ml of ethanol was heated for 2 h under reflux. The
mixture was allowed to cool down to room tempera-
ture and was left overnight. The precipitate was fil-
tered off and recrystallized from dioxane. Yield 58%,
yellow crystals, mp >300°C. IR spectrum, ν, cm–1:
1
3300, 3180 (NH); 2200 (CN); 1600 (C=C). H NMR
b. A mixture of 0.005 mol of compound IV and
0.005 mol of phenyl isothiocyanate in 30 ml of anhy-
drous pyridine was heated for 2 h under reflux. The
mixture was allowed to cool down to room tempera-
ture, poured into cold water, and neutralized with
dilute hydrochloric acid for complete precipitation.
The precipitate was filtered off, washed with water,
dried, and recrystallized from ethanol–DMF (3:1).
Compounds IIIa–IIIc obtained in such a way were
fully identical to samples isolated as described in a.
spectrum (DMSO-d6), δ, ppm: 5.60 s (1H, 6-H), 7.10–
7.80 m (10H, Harom), 8.30 s (1H, NH, exchanges with
D2O), 9.20 s (1H, NH, exchanges with D2O). Mass
spectrum, m/z (Irel, %): 367 [M]+ (88). Found, %:
C 68.44; H 3.64; N 19.18. C21H13N5S. Calculated, %:
C.65; H 3.57; N 19.06. M 367.43.
N-[4-(Dicyanomethylidene)-1-phenyl-2-thioxo-
1,2,3,4-tetrahydropyrimidin-6-yl]acetamide (VII).
A mixture of 0.005 mol of 6-aminopyrimidine II and
10 ml of acetic anhydride was heated for 4 h at 80–
85°C on an oil bath. After cooling to room tempera-
ture, the precipitate was filtered off and recrystallized
from ethanol. Yield 73%, yellow crystals, mp 260–
262°C. IR spectrum, ν, cm–1: 3205 (NH), 2200 (CN),
[6-Amino-1-phenyl-5-(phenyldiazenyl)-2-thioxo-
1,2,3,4-tetrahydropyrimidin-4-ylidene]malononi-
trile (IIIa). Yield 65%, red crystals, mp >300°C. IR
spectrum, ν, cm–1: 3394, 3301, 3236 (NH2, NH); 2229
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SYNTHESIS OF NEW PURINE, PTERIDINE, AND OTHER PYRIMIDINE DERIVATIVES
447
1
1676 (CO). H NMR spectrum (DMSO-d6), δ, ppm:
2.10 s (3H, CH3), 6.90 s (1H, 5-H), 7.00–7.40 m (5H,
Harom), 8.75 s (1H, NH), 10.60 s (1H, NH). Mass spec-
trum, m/z (Irel, %): 309 [M]+ (24). Found, %: C 58.33;
H 3.50; N 22.56. C15H11N5OS. Calculated, %: C 58.24;
H 3.58; N 22.64. M 309.35.
concentrated hydrochloric acid in 20 ml of water was
added, and the mixture was heated for 1 h on a boiling
water bath and cooled. The precipitate was filtered off,
washed with acetone, and dried. Yield 56%, yellow
powder. IR spectrum, ν, cm–1: 3374–3176 (NH2, NH),
2216 (CN). Found, %: C 48.76; H 3.52; N 26.26.
C13H11ClN6S. Calculated, %: C 48.98; H 3.48; N 26.36.
M 318.78.
(6-Cyano-7-methylsulfanyl-5-oxo-1-phenyl-2-
thioxo-1,2,3,4,5,8-hexahydropyrido[2,3-d]pyrimi-
din-4-ylidene)malononitrile (IX). A mixture of
0.01 mol of compound II, 0.01 mol of ethyl 3,3-bis-
(methylsulfanyl)-2-cyanoprop-2-enoate (VIII), and
4 drops of triethylamine in 20 ml of DMF was heated
for 4 h under reflux. After cooling to room tempera-
ture, the precipitate was filtered off and recrystallized
from dioxane. Yield 52%, brown crystals, mp >300°C.
IR spectrum, ν, cm–1: 3330 (NH), 2216 (CN), 1700
(3-Phenyl-2-thioxo-1,2,3,6-tetrahydro-9H-purin-
6-ylidene)malononitrile (XII). A suspension of
0.01 mol of 5,6-daminopyrimidine hydrochloride XI in
20 ml of formic acid was heated for 2 h under reflux.
The mixture was cooled, and the precipitate was
filtered off, thoroughly washed with water and cold
ethanol, and recrystallized from ethanol. Yield 69%,
colorless crystals, mp >300°C. IR spectrum, ν, cm–1:
3310 (NH), 2210 (CN). 1H NMR spectrum (DMSO-d6),
δ, ppm: 7.00–7.50 m (5H, Harom), 8.05 s (1H, 8-H),
8.55 s (1H, NH), 12.20 s (1H, NH). Mass spectrum,
m/z (Irel, %): 292 [M]+ (38). Found, %: C 57.73;
H 2.84; N 28.65. C14H8N6S. Calculated, %: C 57.52;
H 2.76; N 28.75. M 292.32.
1
(C=O), 1550–1590 (C=C). H NMR spectrum
(DMSO-d6), δ, ppm: 2.60 s (3H, SCH3), 7.20–8.00 m
(5H, Harom), 8.40 s (1H, NH, exchanges with D2O),
9.60 s (1H, NH, exchanges with D2O). Mass spectrum,
m/z (Irel, %): 390 [M]+ (74). Found, %: C 55.59;
H 2.63; N 21.41. C18H10N6OS2. Calculated, %: C55.37;
H 2.58; N 21.52. M 390.44.
4-Dicyanomethylidene-7-oxo-1-phenyl-2-thioxo-
1,2,3,4,7,8-hexahydropteridines XIIIa and XIIIb
(general procedure). Ethyl acetoacetate or diethyl
malonate, 0.01 mol, was added to a solution of sodium
ethoxide prepared from 0.01 mol of metallic sodium
and 30 ml of anhydrous ethanol. The mixture was
stirred for 30 min at room temperature, 0.01 mol of
nitroso compound X was added, and the mixture was
heated for 6 h under reflux, cooled to room tempera-
ture, and poured into ice water. The precipitate was
filtered off and recrystallized from ethanol.
(6-Amino-5-nitroso-1-phenyl-2-thioxo-1,2,3,4-
tetrahydropyrimidin-4-ylidene)malononitrile (X).
A solution of 0.01 mol of sodium nitrite in 10 ml of
water was added dropwise under vigorous stirring to
a suspension of 0.01 mol of compound II in 30 ml of
glacial acetic acid. A red solid separated. The mixture
was stirred for 4 h at room temperature, and the precip-
itate was filtered off, washed with water, and recrys-
tallized from ethanol. Yield 84%, orange crystals,
mp 252–253°C. IR spectrum, ν, cm–1: 3420–3280
1
(NH2), 3220 (NH), 2220 (CN). H NMR spectrum
(6-Acetyl-7-oxo-1-phenyl-2-thioxo-1,2,3,4,7,8-
hexahydropteridin-4-ylidene)malononitrile (XIIIa).
Yield 70%, yellow crystals, mp 248°C. IR spectrum,
ν, cm–1: 3295 (NH); 2210 (CN); 1715, 1680 (CO).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.10 s (3H,
CH3), 7.10–7.40 m (5H, Harom), 8.15 s (1H, NH),
12.55 s (1H, NH). Mass spectrum, m/z (Irel, %): 362
[M]+ (62). Found, %: C 56.24; H 2.71; N 23.27.
C17H10N6O2S. Calculated, %: C 56.35; H 2.78; N 23.19.
M 362.37.
(CDCl3), δ, ppm: 7.10–7.40 m (5H, Harom), 8.15 s (1H,
NH), 11.10 s (2H, NH2). Mass spectrum, m/z (Irel, %):
296 [M]+ (20). Found, %: C 52.84; H.63; N 28.44.
C13H8N6OS. Calculated, %: C 52.70; H 2.72; N 28.36.
M 296.31.
(5,6-Diamino-1-phenyl-2-thioxo-1,2,3,4-tetra-
hydropyrimidin-4-ylidene)malononitrile hydro-
chloride (XI). A suspension of 0.02 mol of 6-amino-5-
nitrosopyrimidine X in 50 ml of hot distilled water was
heated on a boiling water bath, and 1.25 g of sodium
dithionite was added in portions over a period of
15 min. The mixture lost its color and was stirred for
15 min on heating using a mechanical stirrer and
allowed to cool down. The precipitate of 5,6-diamino-
pyrimidine bisulfite was filtered off, dried, and trans-
ferred into a three-necked flask. A solution of 50 ml of
Ethyl 4-dicyanomethylidene-7-oxo-1-phenyl-2-
thioxo-1,2,3,4,7,8-hexahydropteridine-6-carbox-
ylate (XIIIb). Yield 66%, yellow crystals, mp >300°C.
IR spectrum, ν, cm–1: 3310 (NH); 2208 (CN); 1705,
1
1680 (CO). H NMR spectrum (DMSO-d6), δ, ppm:
1.25 t (3H, CH3), 4.10 q (2H, CH2), 7.10–7.50 m (5H,
Harom), 8.10 s (1H, NH), 12.60 s (1H, NH). Mass spec-
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ABDEL-LATIF et al.
448
trum, m/z (Irel, %): 392 [M]+ (84). Found, %: C 55.22;
H 3.13; N 21.57. C18H12N6O3S. Calculated, %: C 55.10;
H 3.08; N 21.42. M 392.39.
11. Mittelbach, M., Monatsh. Chem., 1985, vol. 116, p. 689.
12. Perrissin, M., Favre, M., Luu-Duc, C., Huguet, F.,
Gaultier, C., and Narcisse, G., Eur. J. Med. Chem.,
1988, vol. 23, p. 453.
13. Cannito, A., Perrissin, M., Luu-Duc, C., Huguet, F.,
Gaultier, C., and Narcisse, G., Eur. J. Med. Chem.,
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