Synthesis and study of new derivatives of 6-[methoxy(phenyl)methyl]-2- (nitroamino)pyrimidin-4(3H)-one

Article abstract of DOI:10.1007/s11172-013-0020-6

New 6-[(2,6-dihalophenyl)(methoxy)methyl]-5-methyl-2-(nitroamino)pyrimidin- 4(3H)-ones were synthesized by an original and efficient method involving regioselective O,O′-dimethylation of substituted mandelic acids in superbasic medium. The compounds obtained can serve as precursors to a novel series of non-nucleoside HIV-1 replication inhibitors.

Full text of DOI:10.1007/s11172-013-0020-6

Russian Chemical Bulletin, International Edition, Vol. 62, No. 1, pp. 138—141, January, 2013
138
Synthesis and study of new derivatives of
6ꢀ[methoxy(phenyl)methyl]ꢀ2ꢀ(nitroamino)pyrimidinꢀ4(3H)ꢀone
I. A. Novakov, B. S. Orlinson, I. Yu. Kameneva, E. K. Zakharova, and M. B. Nawrozkij
Volgograd State Technical University,
28 prosp. Lenina, 400005 Volgograd, Russian Federation.
Fax: +7 (844) 223 8125. Eꢀmail: kholstaedt@yandex.ru
New 6ꢀ[(2,6ꢀdihalophenyl)(methoxy)methyl]ꢀ5ꢀmethylꢀ2ꢀ(nitroamino)pyrimidinꢀ4(3H)ꢀ
ones were synthesized by an original and efficient method involving regioselective O,O´ꢀdiꢀ
methylation of substituted mandelic acids in superbasic medium. The compounds obtained can
serve as precursors to a novel series of nonꢀnucleoside HIVꢀ1 replication inhibitors.
Key words: 6ꢀ[methoxy(phenyl)methyl]ꢀ2ꢀ(nitroamino)pyrimidinꢀ4(3H)ꢀones, 2ꢀ(2,6ꢀdiꢀ
halophenyl)ꢀ2ꢀhydroxyacetic acids, 3ꢀoxo esters, nitroguanidine.
As a next step in our previous investigations into the
target products and makes their isolation in the individual
state more difficult.3 To increase the yield and purity of
the corresponding derivatives, we proposed 2ꢀ(nitroꢀ
amino)pyrimidinꢀ4(3H)ꢀones7 as the starting materials.
synthesis of novel nonꢀnucleoside derivatives of 6ꢀ(arylꢀ
methyl)pyrimidinꢀ4(3H)ꢀone and study of their antiviral
properties,1 we obtained new functionalized derivatives of
this series (1a—c) that contain the methoxy group in the
ꢀposition of the benzyl radical.
Results and Discussion
2ꢀ(Nitroamino)pyrimidines were synthesized from
mandelic acid derivatives, viz., 2ꢀ(2,6ꢀdifluorophenyl)ꢀ2ꢀ
hydroxyacetic acid (2a),8 2ꢀ(2ꢀchloroꢀ6ꢀfluorophenyl)ꢀ2ꢀ
hydroxyacetic acid (2b),9 and 2ꢀ(2,6ꢀdichlorophenyl)ꢀ2ꢀ
hydroxyacetic acid (2c).10 These starting compounds were
transformed into the corresponding 2ꢀmethoxylated anaꢀ
logs according to a procedure described earlier11 for
the conversion of 2ꢀhydroxyꢀ3ꢀmethylbutanoic acid into
methyl 2ꢀmethoxyꢀ3ꢀmethylbutanoate: compounds 2a—c
were alkylated with MeI in the superbasic system
MeS(O)CH2Li—Me2SO (Scheme 1). The target products
(>95% purity) were obtained in high yields and isolated
simply by extraction of the reaction mixture.
R1 = R2 = F (a); R1 = F; R2 = Cl (b); R1 = R2 = Cl (c)
These compounds were synthesized as possible preꢀ
cursors to the corresponding 2ꢀ(dialkylamino)ꢀ6ꢀ[(2,6ꢀdiꢀ
halophenyl)(methoxy)methyl]ꢀ5ꢀmethylpyrimidinꢀ4(3H)ꢀ
ones, analogs of the highly efficient antiꢀHIVꢀ1 agents
obtained earlier.2,3 Since conformationally hindered deꢀ
rivatives of this series exhibit higher antiviral activity, we
found it expedient to study how the antiviral properties of
a compound vary with the hydrophilicꢀlipophilic balance
of its molecule (when moving from 6ꢀ[1ꢀ(2,6ꢀdihaloꢀ
phenyl)ethyl]ꢀ5ꢀmethylpyrimidinꢀ4(3H)ꢀones to the corꢀ
responding methoxylated analogs).
Scheme 1
The earlier reported synthesis of 6ꢀbenzylisocytosine
derivatives by aminolysis of appropriate 6ꢀbenzylꢀ2ꢀ
(methylsulfanyl)pyrimidinꢀ4(3H)ꢀones is not versatile:
good results were achieved with primary amines in 2ꢀethꢀ
oxyethanol4 and 2ꢀ(ethoxyethoxy)ethanol,5,6 while the use
of secondary aliphatic amines decreases the yields of the
Reagents and conditions: MeI/MeS(O)CH2Li; Me2SO.
2, 3: R1 = R2 = F (a); R1 = F; R2 = Cl (b); R1 = R2 = Cl (c)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0139—0143, January, 2013.
1066ꢀ5285/13/6201ꢀ138 © 2013 Springer Science+Business Media, Inc.

Precursors to novel antiretroviral agents
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 1, January, 2013
139
Scheme 2
GCꢀMS analysis in the EI mode (70 eV) failed to deꢀ
tect the molecular ions of the compounds obtained; yet
this was done by applying chemical ionization. The mass
spectrum of each ester features the corresponding ꢀmethꢀ
oxybenzyl cation.
The IR spectra of these compounds show a band at
1769 cm–1, which is not very typical of the ester CO group.
Such a band is known to be more characteristic of carbꢀ
oxylic acid anhydrides, imidazolides, and chlorides. Obviꢀ
ously, this is due to the influence of the methoxy group in
the ꢀposition relative to the carbonyl and is reflected in
the high hydrolability of the corresponding esters.
Basic hydrolysis of esters 3a—c followed by acidifiꢀ
cation of the reaction mixture afforded the correspondꢀ
ing acids employed in further transformations without puꢀ
rification.
Interestingly, attempted synthesis of esters 3a—c by
methylation of appropriate mandelic acids in the presence
of K2CO312 was not very successful. We obtained complex
mixtures of methylation products, which made isolation
of the target compounds laborious and inefficient.
In the study of the synthesis of ethyl 4ꢀ(2,6ꢀdihaloꢀ
phenyl)ꢀ4ꢀmethoxyꢀ2ꢀmethylꢀ3ꢀoxobutanoates 4a—c, we
demonstrated that these esters are highly thermolabile and
decompose when purified by distillation under reduced
pressure. In addition, ionization of these compounds proꢀ
duces no molecular ions, either by electron impact (the
ꢀmethoxybenzyl cation is detected) or by chemical reꢀ
agents (the fragmentation ion [M – OMe]+ is detected).
To avoid purifying these compounds by column chromatoꢀ
graphy, we developed a synthetic approach by modifying
our previous method.13 Acids 5a—c were transformed into
the corresponding acid chlorides by reactions with SOCl2
at room temperature (because the ꢀmethoxybenzyl moiety
is unstable when exposed to strong Lewis acids). The reꢀ
sulting acid chlorides were used without further purificaꢀ
tion for the synthesis of the corresponding 3ꢀoxo esters
4a—c (Scheme 2).
Reagents and conditions: i. 1) KOH—H2O; 2) HCl—H2O.
ii. SOCl2. iii. 1) (BrMgO)2C=C(Me)COOEt/THF; 2) HCl—H2O.
3—5: R1 = R2 = F (a); R1 = F; R2 = Cl (b); R1 = R2 = Cl (c)
Scheme 3
Reagents and conditions: 1) H2NC(NH)NHNO2/KOEt—EtOH;
2) AcOH—H2O.
1, 4: R1 = R2 = F (a); R1 = F; R2 = Cl (b); R1 = R2 = Cl (c)
It should be noted that highꢀpurity 3ꢀoxo esters 4a—c
were obtained in good yields and isolated simply by exꢀ
traction. GCꢀMS analysis revealed that these compounds
containing two chiral centers exist as two pairs of diastereoꢀ
mers in dynamic equilibrium. The latter phenomenon arisꢀ
es from possible changes (due to ketoꢀenol tautomerism)
of the configuration of the chiral C(2) center.
The target 2ꢀ(nitroamino)pyrimidinꢀ4(3H)ꢀones 1a—c
were obtained by cyclocondensation of 3ꢀoxo esters 4a—c
with nitroguanidine in the presence of a solution of KOEt
in anhydrous EtOH and isolated in the individual state by
precipitation with AcOH from aqueous basic solutions
(Scheme 3).
method allows isolation of both the target products and
intermediates in the individual state without using laboriꢀ
ous and inefficient techniques of purification. The yields
of the key intermediates, viz., methyl 2ꢀ(2,6ꢀdihalopheꢀ
nyl)ꢀ2ꢀmethoxyacetates and ethyl 4ꢀ(2,6ꢀdihalophenyl)ꢀ
4ꢀmethoxyꢀ2ꢀmethylꢀ3ꢀoxobutanoates, are nearly quanꢀ
titative.
Experimental
GLCꢀMS analysis was performed on a Varian Saturn 2100
instrument. For esters 3a,b and 4a—c, m/z values are cited only for
molecular ions and fragmentation ions containing 35Cl isotopes.
1H NMR spectra were recorded on a Varian Mercury 300 BB instꢀ
rument (300 MHz); chemical shifts are referenced to HMDS as
To sum up, we proposed a convenient route to new
6ꢀ[(2,6ꢀdihalophenyl)(methoxy)methyl]ꢀ5ꢀmethylꢀ2ꢀ
(nitroamino)pyrimidinꢀ4(3H)ꢀones, precursors to a novel
series of nonꢀnucleoside HIVꢀ1 replication inhibitors. This

140
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 1, January, 2013
Novakov et al.
the internal standard. IR spectra were recorded on a Specord Mꢀ82
spectrometer (Nujol). Melting points were determined on a Fishꢀ
(s, 3 H, OMe); 5.14 (s, 1 H, CH); 6.86—6.93 (m, 2 H, HAr(3),
HAr(5)), 7.25—7.33 (m, 1 H, HAr(4)); 9.00 (br.s, 1 H, COOH).
2ꢀ(6ꢀChloroꢀ2ꢀfluorophenyl)ꢀ2ꢀmethoxyacetic acid (5b) was
obtained as described for acid 5a from ester 3b. Yield 93%.
Found (%): C, 49.41; H, 3.70; Cl, 16.20; F, 8.74. C9H8O3FCl
(M = 218.61). Calculated (%): C, 49.45; H, 3.69; Cl, 16.22;
F, 8.69. 1H NMR (CDCl3), : 3.39 (s, 3 H, OMe); 5.32 (s, 1 H,
CH); 7.19 (t, 1 H, HAr(4), J = 8.8 Hz); 7.26 (d, 2 H, HAr(3),
HAr(5), J = 8.3 Hz); 8.07 (br.s, 1 H, COOH).
er—Jones hot stage (Cole Palmer) at a heating rate of 10C min–1
.
TLC analysis was carried out on POLYGRAMSILG/UV254
plates (aluminum substrate coated with silica gel, MACHEREYꢀ
NAGEL GmbH&Co. KG) with C6H14—THF—MeOH
(12 : 3 : 1, v/v) as an eluent; spots were visualized under UV
light. Reaction mixtures and extracts were concentrated on
a Heidolph Laborota 4000 rotary evaporator (~20 Torr). Organic
extracts were dried with MgSO4. All the starting reagents were
purchased from Aldrich, Acros, or Lancaster Synthesis. Solvents
were additionally purified and dried according to known proceꢀ
dures.14 Samples prepared for physicochemical studies, as well
as nitroguanidine containing ballast water, were dried in high
vacuum over P2O5 for 20 h at 25—110 C, depending on the
melting point of the sample.
2ꢀ(2,6ꢀDichlorophenyl)ꢀ2ꢀmethoxyacetic acid (5c) was obꢀ
tained as described for acid 5a from ester 3c. Yield 98%, m.p.
120—122 C (from cyclohexane). Found (%): C, 46.01; H, 3.45;
Cl, 30.20. C9H8O3Cl2 (M = 235.06). Calculated (%): C, 45.99;
1
H, 3.43; Cl, 30.16. H NMR (CDCl3), : 3.39 (s, 3 H, OMe);
5.60 (s, 1 H, CH); 6.94 (t, 1 H, HAr(4), J = 9.7 Hz); 7.16—7.25
(m, 2 H, HAr(3), HAr(5)); 10.62 (s, 1 H, COOH).
Methyl 2ꢀ(2ꢀchloroꢀ6ꢀfluorophenyl)ꢀ2ꢀmethoxyacetate (3b).
A 2.5 M solution of BunLi (137.5 mmol) in hexane (55 mL) was
slowly added under dry nitrogen to anhydrous DMSO (90 mL)
while stirring and cooling it. Stirring was continued for another
5—10 min. Then a solution of acid 2b (13.46 g, 65.8 mmol) in
anhydrous DMSO (90 mL) was added dropwise with stirring and
cooling. The mixture was stirred at room temperature for 2.5 h
and cooled again, whereupon MeI (9.4 mL, 21.41 g, 150.8 mmol)
was added dropwise with stirring. The stirring was continued for
another ~1.5 h. The reaction mixture was left at room temperaꢀ
ture for 16 h and poured into water (500 mL). Organic materials
were extracted with Et2O (3×150 mL). The combined organic
extracts were washed with brine (3×75 mL), dried, filtered,
and concentrated. The yield of crude ester 3b (95.2% purity,
GLCꢀMS) was 97%. This product was distilled to give ester 3b
(14.65 g, 86%) with 98.8% purity (Rt = 11.268 min, GLCꢀMS),
n20D = 1.5116, b.p. 109—111 C (2 Torr). Found (%): C, 51.60;
H, 4.39; Cl, 15.14; F, 8.27. C10H10O3FCl (M = 232.64). Calcuꢀ
lated (%): C, 51.63; H, 4.33; Cl, 15.24; F, 8.17. MS (EI, 70 eV),
m/z: 173.2 [M – COOMe]+ (100). MS (CI), m/z: 233.0 [M + 1]+
(100), 173.0 [M – COOMe]+ (35).
Ethyl 4ꢀ(2ꢀchloroꢀ6ꢀfluorophenyl)ꢀ4ꢀmethoxyꢀ2ꢀmethylꢀ3ꢀ
oxobutanoate (4b). Thionyl chloride (100 mL, 165.5 g, 1.39 mol)
was added to acid 5b (11.11 g, 50.8 mmol). Then several drops
of anhydrous DMF were added. The reaction mixture was
stirred at room temperature for 24 h and concentrated. Toluene
(2×75 mL) was added to the residue and then distilled off. The
resulting crude acid chloride was not purified prior to subsequent
transformations.
A solution of PriMgBr prepared from metallic Mg (6.79 g,
279.2 mgꢀatom) and PriBr (24 mL, 31.44 g, 255.6 mmol) in
anhydrous THF (150 mL) was added dropwise to a cooled and
stirred solution of EtOOCCH(Me)COOH (14.85 g, 101.6 mmol)
in anhydrous THF (75 mL). The mixture was stirred for another
20 min and cooled to –8 C. Then a solution of the crude acid
chloride in anhydrous THF (50 mL) was added dropwise at 0 C
over 1 h, while keeping the reaction mixture stirred. Stirring was
continued at 0 C for 1 h and then at room temperature for 1 h.
The reaction mixture was poured into a stirred mixture of conc.
HCl (35 mL) and crushed ice (70 g) and stirring was continꢀ
ued until the ice melted completely. The product was extracted
with diethyl ether (3×200 mL). The combined extracts
were washed with water (to pH 4—5), 5% aqueous K2CO3 (when
acidified, these extracts return up to 80% of the excess
EtOOCCH(Me)COOH), again water to a neutral reaction, and
brine (3×100 mL). The washed organic solution was dried, filꢀ
tered through a short (5—7 mm) column with silica gel for TLC,
and concentrated. The yield of the target ester 4b was 15.30 g
(99%). The content of the title component was 95.0% (two pairs
of diastereomers with Rt = 15.101 min (51.0%) and Rt = 15.422 min
(44.0%), GLCꢀMS). Found (%): C, 55.60; H, 5.30; Cl, 11.72;
F, 6.28. C14H16O4FCl (M = 302.73). Calculated (%): C, 55.55;
H, 5.33; Cl, 11.71; F, 6.28. MS (EI, 70 eV), m/z: 173.2
[M – C(O)CH(Me)COOC2H5]+ (100). MS (CI), m/z: 271.0
[M – OMe]+ (100).
Methyl 2ꢀ(2,6ꢀdifluorophenyl)ꢀ2ꢀmethoxyacetate (3a) was
obtained as described above for ester 3b from acid 2a. Yield 86%,
purity 96.0% (Rt = 9.197 min, GLCꢀMS). Found (%): C, 55.60;
H, 4.70; F, 17.48. C10H10O3F2 (M = 216.18). Calculated (%):
C, 55.56; H, 4.66; F, 17.58. MS (EI, 70 eV), m/z: 157.1
[M – COOMe]+ (100). MS (CI), m/z: 217.0 [M + 1]+ (100),
157.1 [M – COOMe]+ (36).
Methyl 2ꢀ(2,6ꢀdichlorophenyl)ꢀ2ꢀmethoxyacetate (3c) was
obtained as described for ester 3b from acid 2c. Yield 92%, purity
99.4% (Rt = 13.159 min, GLCꢀMS), m.p. 95—96 C (from hexꢀ
ane). Found (%): C, 48.20; H, 4.00; Cl, 28.50. C10H10O3Cl2
(M = 249.09). Calculated (%): C, 48.22; H, 4.05; Cl, 28.47. MS
(EI, 70 eV), m/z: 248.8 [M]+ (7), 191.0 [M – COOMe]+ (100). MS
(CI), m/z: 250.0 [M + 1]+ (100), 189.1 [M – COOMe]+ (62).
2ꢀ(2,6ꢀDifluorophenyl)ꢀ2ꢀmethoxyacetic acid (5a). Ester 3a
(10 g, 46.2 mmol) was refluxed with 10% aqueous NaOH (7.4 g,
185.0 mmol) until a transparent solution formed. On cooling,
the product was extracted with diethyl ether (2×50 mL). The
extracts were mixed with Et2O (250 mL) and acidified with conc.
HCl to pH 1. The organic phase was separated, washed with
water (to pH 5), dried, and filtered. The solvent was removed to
give pure acid 5a (1H NMR). Yield 9.19 g (98%). Found (%):
C, 53.51; H, 3.99; F, 18.81. C9H8O3F2 (M = 202.15). Calculatꢀ
Ethyl 4ꢀ(2,6ꢀdifluorophenyl)ꢀ4ꢀmethoxyꢀ2ꢀmethylꢀ3ꢀoxoꢀ
butanoate (4a) was obtained as described for 3ꢀoxo ester 4b from
acid 5a. Yield 94%. Found (%): C, 58.80; H, 5.61; F, 13.30.
C14H16O4F2 (M = 286.27). Calculated (%): C, 58.74; H, 5.63;
F, 13.27. The content of the title component was 98.5% (two
pairs of diastereomers with Rt = 13.376 min (59.6%) and
Rt = 13.713 min (38.9%), GLCꢀMS). MS (EI, 70 eV), m/z: 157.0
[M – C(O)CH(Me)COOC2H5]+ (100). MS (CI), m/z: 254.8
[M – OMe]+ (100).
Ethyl 4ꢀ(2,6ꢀdichlorophenyl)ꢀ4ꢀmethoxyꢀ2ꢀmethylꢀ3ꢀoxoꢀ
butanoate (4c) was obtained as described for 3ꢀoxo ester 4b from
1
ed (%): C, 53.47; H, 3.99; F, 18.80. H NMR (CDCl3), : 3.40

Precursors to novel antiretroviral agents
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 1, January, 2013
141
acid 5c. Yield 98%. Found (%): C, 52.71; H, 5.10; Cl, 22.25.
C14H16O4Cl2 (M = 319.18). Calculated (%): C, 52.68; H, 5.05;
Cl, 22.22. The content of the title component was 96.4%
(two pairs of diastereomers with Rt = 16.722 min (38.9%) and
Rt = 17.052 min (57.5%), GLCꢀMS). MS (EI, 70 eV), m/z: 191.0
[M – C(O)CH(Me)COOC2H5]+ (100). MS (CI), m/z: 287.3
[M – OMe]+ (100).
inꢀ4(3H)ꢀones", Application No. 2012ꢀ1.2.2ꢀ12ꢀ000ꢀ
1004ꢀ007).
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6ꢀ[(2,6ꢀDichlorophenyl)(methoxy)methyl]ꢀ5ꢀmethylꢀ2ꢀ(nitroꢀ
amino)pyrimidinꢀ4(3H)ꢀone (1c). Nitroguanidine (3.26 g,
31.3 mmol) and ester 4c (10 g, 31.3 mmol) were added to
a solution of KOEt prepared from metallic potassium (2.44 g,
62.6 mgꢀatom) and anhydrous EtOH (250 mL). The reaction
mixture was refluxed with stirring for 18 h and concentrated.
The residue was dissolved in water (300 mL). Organic materials
were extracted with diethyl ether (3×75 mL). The aqueous phase
was neutralized with AcOH with stirring. The precipitate that
formed was filtered off, washed with water (3×75 mL), cold
EtOH (50 mL), and Et2O (3×25 mL), squeezed on the filter, and
dried to a constant weight. The yield of the target product 1c was
3.71 g (33%), crystalline powder, m.p. 230.5—231.0 C, Rf 0.26.
Found (%): C, 43.55; H, 3.41; Cl, 19.80; N, 15.70. C13H12N4O4Cl2
(M = 359.16). Calculated (%): C, 43.47; H, 3.37; Cl, 19.74;
N, 15.60. 1H NMR (DMSOꢀd6), : 1.42 (s, 3 H, Me); 3.44 (s, 3 H,
OMe); 6.20 (s, 1 H, CH); 7.51 (t, 1 H, H(4)Ar, J = 6.7 Hz); 7.61
(d, 2 H, HAr(3), HAr(5), J = 6.7 Hz); 12.71 (s, 1 H, NH); 12.91
(s, 1 H, NH).
6ꢀ[(2,6ꢀDifluorophenyl)(methoxy)methyl]ꢀ5ꢀmethylꢀ2ꢀ(nitroꢀ
amino)pyrimidinꢀ4(3H)ꢀone (1a) was obtained as described for
compound 1c from 3ꢀoxo ester 4a. Neutralization of the aqueous
solution resulted in oil formation. The oil was extracted with
EtOAc (3×150 mL). The combined organic extracts were washed
with water (4×75 mL) and brine (3×100 mL), dried, filtered, and
concentrated. The residue was purified by recrystallization from
MeOH with activated charcoal (1 g). Yield 25%, m.p. 282—284 C
(decomp.), Rf 0.22. Found (%): C, 47.80; H, 3.70; F, 11.70;
N, 17.24. C13H12N4O4F2 (M = 326.26). Calculated (%): C, 47.86;
H, 3.71; F, 11.65; N, 17.17. 1H NMR (DMSOꢀd6), : 1.65
(s, 3 H, Me); 3.43 (s, 3 H, OMe); 5.92 (s, 1 H, CH); 7.21 (t, 2 H,
HAr(3), HAr(5), J = 9.7 Hz); 7.52—7.62 (m, 1 H, HAr(4)); 12.60
(s, 1 H, NH); 12.88 (s, 1 H, NH).
6ꢀ[(2ꢀChloroꢀ6ꢀfluorophenyl)(methoxy)methyl]ꢀ5ꢀmethylꢀ2ꢀ
(nitroamino)pyrimidinꢀ4(3H)ꢀone (1b) was obtained as described
for compound 1c from 3ꢀoxo ester 4b. Yield 26%, m.p.
201.5—202.5 C (decomp.), Rf 0.25. Found (%): C, 45.61;
H, 3.60; Cl, 10.42; F, 5.54; N, 16.42. C13H12N4O4FCl (M =
= 342.71). Calculated (%): C, 45.56; H, 3.53; Cl, 10.34; F, 5.54;
N, 16.35. 1H NMR (DMSOꢀd6), : 1.56 (s, 3 H, Me); 3.45 (s, 3 H,
OMe); 6.00 (s, 1 H, CH); 7.33 (t, 1 H, HAr(4), J = 10.0 Hz);
7.52—7.59 (m, 2 H, HAr(3), HAr(5)); 12.64 (s, 1 H, NH); 12.91
(s, 1 H, NH).
12. GB Pat. 1963922371, 1963; http://worldwide.espacenet.
com/publicationDetails/originalDocument?CC=GB&N
R=922371A&KC=A&FT=D&ND=3&date=19630327&
DB=worldwide.espacenet.com&locale=en_EP.
13. RU Pat. 20112412154, 2011; http://worldwide.espacenet.
com/publicationDetails/biblio?FT=D&date=20110220&
DB=worldwide.espacenet.com&locale=enEP&CC=RU
&NR=2412154C1&KC=C1&ND=5.
14. L. Tietze, T. Eicher, Reaktionen und Synthesen im organischꢀ
chemischen Praktikum und Forschungslaboratorium, Georg
Thieme Verlag, Stuttgart—New York, 1991.
This work was financially supported by the Ministry of
Education and Science (Federal Target Program "Sciꢀ
entific and ScientificꢀPedagogical Personnel of the Inꢀ
novative Russia in 2009—2013", Grant 14.V37.21.0826
"Design of Highly Efficient NonꢀNucleoside Antiꢀ
HIVꢀ1 Agents on the Basis of Functionalized Pyrimidꢀ
Received November 20, 2012;
in revised form December 29, 2012