Synthesis of trichloromethylpyrimidines and trichloromethylpyrimido [4,5-d]pyrimidines from alkyl 2-(diaminomethylidene)-3-oxobutyrates and trichloroacetonitrile

Article abstract of DOI:10.1007/s11172-010-0015-5

Heterocyclization of alkyl 2-(diaminomethylidene)-3-oxobutyrates with trichloroacetonitrile yields alkyl 4-mino-6-methyl-2-trichloromethylpyrimidine- 5-carboxylates. The latter compounds react with aryl isocyanates to produce the corresponding pyrimidinyl

Full text of DOI:10.1007/s11172-010-0015-5

Russian Chemical Bulletin, International Edition, Vol. 58, No. 2, pp. 351—355, February, 2009
351
Synthesis of trichloromethylpyrimidines and trichloromethylpyrimidoꢀ
[4,5ꢀd]pyrimidines from alkyl 2ꢀ(diaminomethylidene)ꢀ
3ꢀoxobutyrates and trichloroacetonitrile*
V. A. Voronkova, A. V. Komkov, and V. A. Dorokhov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: vador@ioc.ac.ru
Heterocyclization of alkyl 2ꢀ(diaminomethylidene)ꢀ3ꢀoxobutyrates with trichloroacetoꢀ
nitrile yields alkyl 4ꢀaminoꢀ6ꢀmethylꢀ2ꢀtrichloromethylpyrimidineꢀ5ꢀcarboxylates. The latter
compounds react with aryl isocyanates to produce the corresponding pyrimidinylureas,
which undergo cyclization to 3ꢀarylꢀ5ꢀmethylꢀ7ꢀtrichloromethylpyrimido[4,5ꢀd]pyrimidineꢀ
2,4(1H,3H)ꢀdiones under the action of MeONa in MeOH.
Key words: alkyl 2ꢀ(diaminomethylidene)ꢀ3ꢀoxobutyrates, trichloroacetonitrile, alkyl
4ꢀaminoꢀ6ꢀmethylꢀ2ꢀtrichloromethylpyrimidineꢀ5ꢀcarboxylates, 7ꢀtrichloromethylpyrimidoꢀ
[4,5ꢀd]pyrimidineꢀ2,4(1H,3H)ꢀdiones, heterocyclization.
Scheme 1
α,αꢀDioxoketene aminals are convenient starting
reagents for the synthesis of nitrogenꢀcontaining heteroꢀ
cycles. In the molecules of these compounds, one can
mark out enaminone, enediamine, and βꢀdicarbonyl
fragments, which can take part in different variants of
fiveꢀ and sixꢀmembered ring closure.1—7 In addition, the
approach based on the change in the reactivities of ketene
aminals upon chelation with boron considerably extends
the potential of design of Nꢀheterocycles.8—14
Apparently, the maximum efficiency in the heteroꢀ
cyclization reactions for electronic and steric reasons is to
be expected for ketene aminals containing two unsubꢀ
stituted NH2 groups. Earlier it has been found that
compounds of this kind can react with aroylketenes to
produce 4ꢀpyrimidinone derivatives.15 Herein, we report
on cyclocondensation of alkyl 2ꢀ(diaminomethylidene)ꢀ
3ꢀoxobutyrates with trichloroacetonitrile.
The starting ketene aminals can be obtained directly
by the reaction of cyanamide with the corresponding
acetoacetates in the presence of catalytic amounts of
Ni(acac)2 (see Ref. 16). Instead of cyanamide, in the
reactions with keto esters one can use benzoylcyanamide,
which is more stable on storage and heating. Although in
this case Nꢀbenzoyl derivatives of aminals are formed,
debenzoylation of the latter proceeds smoothly upon treatꢀ
ment with MeONa in MeOH (see Scheme 1).
R = Et (a), Me (b)
i. PhCONHCN, cat. Ni(acac)2; ii. MeONa, MeOH
Compounds 1а and 2а synthesized in this way from
ethyl acetoacetate were described earlier.16 The 1H NMR
spectrum of crystalline Nꢀbenzoylaminal 1b obtained simiꢀ
larly shows one set of signals in DMSOꢀd6 related apparꢀ
ently to the Zꢀisomer. The rotation barrier around the
C=C bond in the analogous pushꢀpull systems is very
low,17 but nevertheless in the spectrum of solution of 1b in
CDCl3 there is a double set of signals (the ratio is ~2 : 1)
because the intramolecular hydrogen N—H⋅⋅⋅O bonds
favoring stabilization of isomers are preserved in this
solvent.
* On the occasion of the 75th anniversary of the foundation
of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 347—351, February, 2009.
1066ꢀ5285/09/5802ꢀ0351 © 2009 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
Voronkova et al.
Compounds 2a,b do not react with nonactivated
2ꢀtrichloromethylpyrimidineꢀ5ꢀcarboxylate has been
mentioned, which is thought18 to be obtained upon reacꢀ
tion of trichloroacetonitrile with alkyl 3ꢀaminoꢀ2,4ꢀdiꢀ
cyanobutꢀ2ꢀenoate. However, later the reaction product
has been identified as a trichloromethylpyridine deriꢀ
vative.19
nitriles (MeCN, PhCN and others). Attempts to carry out
cyclocondensation of ketene aminals 2a,b with trichloroꢀ
acetonitrile in refluxing THF, benzene, or pyridine were
unsuccessful either. Virtually no reaction of ketene aminals
in THF and benzene took place, and intense resinification
was observed in refluxing pyridine. However, it was posꢀ
sible to obtain alkyl 4ꢀaminoꢀ6ꢀmethylꢀ2ꢀtrichloroꢀ
methylpyrimidineꢀ5ꢀcarboxylates 3a,b in 76% and 90%
isolated yields, respectively, by heating the reactants in
toluene in sealed tubes at 115—125 °C (see Scheme 2).
Functionalized pyrimidines 3a,b attracted our attenꢀ
tion as potential starting compounds for the synthesis of
new pyrimidine derivatives. Thus examples of the substiꢀ
tution of the CCl3 group in 4ꢀtrichloromethylquinazoline
under the action of propylamine or pyrrolidine are
known.20 Analogous transformations of compounds 3a,b
would lead to biologically significant diaminopyrimidine
derivatives. However, the reaction of pyrimidine 3а with
benzylamine in a 1 : 1 ratio (reflux in toluene) proceeded
in a more complex way and no formation of the correꢀ
sponding 2ꢀbenzylaminopyrimidine 4 was observed (see
Scheme 3). According to data from mass spectrometry,
1H NMR and IR spectroscopy, the structure 5 should be
assigned to the compound isolated in a low yield followꢀ
ing treatment of the reaction mixture with aqueous EtOH.
Apparently, the transformation of trichloromethylpyriꢀ
midine 3a into amide 5 is the result of an attack by the
amine on the CCl3 group and the subsequent hydrolysis of
the substitution product (cf. Refs 21,22).
Scheme 2
Scheme 3
R = Et (a), Me (b)
i. Toluene, 115—125 °C.
Obviously, enaminones 2a,b add to the C≡N bond of
the nitrile as Nꢀnucleophiles and the adducts obtained
afford pyrimidines 3a,b as a result of intramolecular conꢀ
densation under the reaction conditions. Expectedly,
elimination of water rather than an alcohol occurs, that
is, it is the acetyl group, which is more reactive than the
alkoxycarbonyl group, that is involved in the cyclization.
Trichloromethylpyrimidines 3a,b are white crystalline
substances well soluble in organic solvents except for
petroleum ether. Their structures were confirmed by
spectroscopic data. The mass spectra show peaks of the
i. PhCH2NH2, toluene, Δ.
The presence of vicinal NH2 и COOR groups is favorꢀ
able for the second nitrogenꢀcontaining ring annulation.
Previously23, we have reported that the reaction of alkyl
4ꢀaminoꢀ2ꢀacetylaminopyrimidineꢀ5ꢀcarboxylates with
phenyl isocyanate yielded pyrimido[4,5ꢀd]pyrimidine
derivatives via the corresponding ureas. Trichloromethylꢀ
pyrimidine 3a also reacts with aryl isocyanate in refluxing
toluene. However, the reaction rate is comparatively low
and the excess of isocyanate is required. Thus, ureas 6a,b
were obtained in 63ꢀ85% isolated yields, that is, the presꢀ
ence of the electronꢀwithdrawing CCl3 group in aminoꢀ
pyrimidines 3a,b does not prevent the latter from addition
1
molecular ions. In the H NMR spectra, signals for
the alkoxycarbonyl groups and a broadened singlet for the
NH2 group (2 H) at δ 7.84—7.90 (in DMSOꢀd6) are
observed. The 13C NMR spectra of this compounds
show the most downfield signal at δ ~170 confirming
the absence of the acetyl group. The IR spectra (CHCl3)
show absorption bands of the C=O bond of the alkoxyꢀ
carbonyl fragment (1695 cm–1) and the NH2 group (3500
and 3372 cm–1).
Among compounds similar in structure to trichloroꢀ
methylpyrimidines 3a,b, ethyl 4ꢀaminoꢀ6ꢀcyanomethylꢀ

Synthesis of trichloromethylpyrimidines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 2, February, 2009
353
Scheme 4
R´ = Ph (a), 4ꢀMeC6H4 (b)
i. Toluene, Δ; ii. MeONa, MeOH, 20 °C.
obtained from methyl acetoacetate and benzoylcyanamide
according to a previously reported method29 in a yield of 67%,
m.p. 117—118 °С (EtOH). Found (%): C, 59.67; H, 5.49;
N, 10.48. C13H14N2O4. Calculated (%): C, 59.53; H, 5.38;
N, 10.68. MS (EI), m/z: 262 [M]+. 1H NMR (CDCl3,
E/Zꢀisomers in a ~2 : 1 ratio), δ: 2.49/2.46 (s, 3 H, Me);
3.81/3.84 (s, 3 H, OМe); 7.60 (m, 3 H, Ph); 8.05 (m, 2 H, Ph);
10.0/11.8 (br.s, 2 H, NH2); 15.70/13.79 (s, 1 H, NH). 1H NMR
(DMSOꢀd6), δ: 2.35 (s, 3 H, Me); 3.75 (s, 3 H, OМe); 7.62 (t,
2 H, mꢀPh, J = 8.0 Hz); 7.72 (t, 1 H, pꢀPh, J = 8.0 Hz); 7.94
(d, 2 H, oꢀPh, J = 8.0 Hz); 9.72 (br.s, 1 H, NH); 10.20, 14.95
(both br.s, 2 H, NH2). Ester 2b was obtained by treatment
of compound 1b with MeONa in MeOH according to the
known method16 in a yield of 95%, m.p. 120—121 °С (benzene).
Found (%): C, 45.54; H, 6.33; N, 17.52. C6H10N2O3. Calcuꢀ
lated (%): C, 45.56; H, 6.37; N, 17.72. MS (EI), m/z: 158 [M]+.
IR, (CHCl3), ν/сm–1: 3480, 3400—2800 (NH); 1656 (CO);
1602. 1H NMR (DMSOꢀd6), δ: 2.20 (s, 3 H, Me); 3.61 (s, 3 H,
OМe); 6.85 (br.s, 2 H, 2 NH); 9.30 (br.s, 2 H, 2NH).
to aryl isocyanates (see Scheme 4). White or yellowish
compounds 6a,b are well soluble in chloroform, acetone,
but poorly soluble in toluene, MeOH, and DMSO. Their
structures were confirmed by the data from IR, 1H NMR,
and 13C NMR, and mass spectra. Ureas 6a,b in turn easily
undergo cyclization into pyrimido[4,5ꢀd]pyrimidineꢀ
2,4ꢀdiones 7a,b, in 79—90% isolated yields under the
action of MeONa in МеОН at 20 °С.
White crystalline compounds 7a,b synthesized are well
soluble in chloroform, acetone, and DMSO. Their strucꢀ
tures were confirmed by spectroscopic data. Thus the mass
spectra show intense peaks of molecular ions. Signals
1
for the ethoxycarbonyl group are absent from the H and
13C NMR spectra. There is a signal for only one NH
group at δ 8.80—8.90 (1H NMR, CDCl3). The IR spectra
(CHCl3) show absorption bands of two carbonyl groups
(744 and 1692—1712 cm–1).
Thus, with the use of esters 2 as reagents of heteroꢀ
cyclic synthesis it is possible to obtain fused pyrimidines
containing trichloromethyl group rather than only triꢀ
chloromethylpyrimidines.
There are patent data dealing with the application
of a number of 2ꢀtrichloromethylpyrimidines as fungiꢀ
cides.24—26 Pyrimido[4,5ꢀd]pyrimidines also represent the
class of heterocyclic compounds that are promising in
biological aspects. In particular, pyrimido[4,5ꢀd]pyrimiꢀ
dineꢀ2,4ꢀdione derivatives possess antiallergic27 and antiꢀ
hypertensive activities.28
Ethyl 4ꢀaminoꢀ6ꢀmethylꢀ2ꢀtrichloromethylpyrimidineꢀ5ꢀcarꢀ
boxylate (3а). A mixture of ketene aminal 2а (0.344 g, 2 mmol)
and CCl3CN (0.40 mL, 4 mmol) in dry toluene (8 mL) was
heated for 16 h in a sealed tube at 115—125 °С. The solvent
was evaporated in vacuo, the residue was chromatographed on a
column with SiO2 (eluent — benzene). Compound 3а was
obtained in a yield of 0.45 (76%), m.p. 113—114 °С (hexane).
Found (%): С, 36.30; Н, 3.53; Cl, 35.68; N, 14.03. C9H10Cl3N3O2.
Calculated (%): С, 36.20; Н, 3.38; Cl, 35.62; N, 14.08. MS (EI)
(hereinafter peaks of ions only for 35Cl isotope are given), m/z
(Irel (%)): 297 [M]+ (14), 262 [M – Cl]+ (65), 252 [M – OEt]+
(20), 36 (100). IR, (CHCl3), ν/сm–1: 3500, 3372 (NH2); 1692
(СО); 1600, 1544. 1H NMR (DMSOꢀd6), δ: 1.30 (t, 3 Н,
МеСН2, J = 7.0 Hz); 2.50 (s, 3 Н, Ме); 4.32 (q, 2 Н, СН2,
J = 7.0 Hz); 7.90 (br.s, 2 Н, NH2). 13C NMR (CDCl3), δ:
14.27 (МеСН2); 26.50 (Ме); 61.87 (СН2); 96.53 (CCl3);
104.26 (С(5)); 164.00, 164.77 (С(2), С(4)); 166.95 (CO2Et);
170.72 (С(6)).
Experimental
1H and 13C NMR spectra were recorded on a Bruker
AMꢀ300 spectrometer, IR spectra were recorded on a SpecordꢀM82
instrument, mass spectra (EI, 70 eV, temperature of ionization
chamber is 250 °С) were obtained on a Kratos MSꢀ30 mass
spectrometer using a direct inlet system. Ketene aminal 2а was
synthesized using the known method.16 Anhydrous toluene
obtained by distillation over metallic sodium, trichloroacetonitrile
and aryl isocyanates (Lancaster) were used in the syntheses.
Column chromatography was carried out using Silica gel 60
(0.063—0.200 mm) (Merck).
Methyl 4ꢀaminoꢀ6ꢀmethylꢀ2ꢀtricloromethylpyrimidineꢀ
5ꢀcarboxylate (3b) was prepared analogously to compound 3а
from ketene aminal 2b and CCl3CN. The yield was 91%,
m.p. 114—115 °С (hexane). Found (%): С, 33.95; Н, 2.97;
Cl, 37.57; N, 14.80. C8H8Cl3N3O2. Calculated (%): C, 33.77;
H, 2.83; Cl, 37.38; N, 14.78. MS (EI), m/z (Irel (%)): 283
[M]+ (33), 252 [M – OМe]+ (37), 251 [M – MeOH]+ (48), 248
[M – Cl]+ (100), 217 [M – Cl – OМe]+ (66). IR, (CHCl3),
1
ν/сm–1: 3500, 3370 (NH2); 1695 (СО); 1602, 1545. H NMR
Methyl 2ꢀ(diaminomethylidene)ꢀ3ꢀoxobutyrate (2b). Methyl
2ꢀ[amino(benzoylamino)methylidene]ꢀ3ꢀoxobutyrate 1b was
(CDCl3), δ: 2.74 (s, 3 Н, Ме); 3.98 (s, 3 Н, ОМе); signals for

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Voronkova et al.
the protons of NH2 group were not recorded in CDCl3 (as in the
case of 3а). 1H NMR (DMSOꢀd6), δ: 2.50 (s, 3 Н, Ме); 3.88 (s,
3 Н, ОМе); 7.84 (br.s, 2 Н, NH2).
5ꢀMethylꢀ3ꢀphenylꢀ7ꢀtrichloromethylpyrimido[4,5ꢀd]pyriꢀ
midineꢀ2,4(1Н,3Н)ꢀdione (7а). A mixture of urea 6а (0.2 g,
0.48 mmol) and MeONa (2.4 mmol) in МеОН (5 mL) was
stirred for 5 min, the homogeneous solution was acidified with
АсОН, the precipitate that formed was filtered off, washed
with hexane. Bicycle 7а was obtained in a yield of 0.14 g (79%),
m.p. 238—240 °С (benzene). Found (%): С, 45.22; Н, 2.46;
Cl, 28.68; N, 15.00. C14H9Cl3N4O2. Calculated (%): C, 45.25;
H, 2.44; Cl, 28.62; N, 15.08. MS (EI), m/z (Irel (%)): 370 [M]+
(46), 335 [M – Cl]+ (20), 119 [PhNCO]+ (100). IR, (CHCl3),
ν/сm–1: 3392 (NH); 1744 (CO); 1692 (CO); 1592, 1572.
1H NMR (CDCl3), δ: 3.08 (s, 3 Н, Ме); 7.30 (d, 2 H, oꢀPh,
J = 8.0 Hz); 7.53 (m, 3 Н, mꢀPh, pꢀPh); 8.80 (br.s, 1 H, NH).
13C NMR (DMSOꢀd6), δ: 24.56 (Me); 95.99 (CCl3); 106.62
(C(4a)); 128.46 (pꢀPh); 128.82, 128.98 (oꢀPh, mꢀPh); 135.10
(ipsoꢀPh); 149.83 (C(2)); 158.37 (C(8a)); 160.71 (C(4)); 164.90
(C(7)); 171.77 (C(5)). The assignment of the signals in the 13C
NMR spectrum was made based on comparison with the
13C NMR spectrum of urea 6a.
5ꢀMethylꢀ3ꢀ(4ꢀtolyl)ꢀ7ꢀtrichloromethylpyrimido[4,5ꢀd]pyriꢀ
midineꢀ2,4(1Н,3Н)ꢀdione (7b). A mixture of urea 6b (0.1 g,
0.23 mmol) and MeONa (1.15 mmol) in MеОН (5 mL) was
stirred for 5 min, the homogeneous solution was acidified with
АсОН, the solvent was evaporated in vacuo. Chloroform (15 mL)
was added to the residue, insoluble sodium acetate was filtered
off, chloroform was evaporated in vacuo, the residue was
recrystallizated from benzene. Bicycle 7b was obtained in a yield
of 0.08 g (90%), m.p. 231—233 °С. Found (%): С, 46.30;
Н, 2.69; Cl, 27.55; N, 14.31. C15Н11Cl3N4O2. Calculated (%):
C, 46.72; H, 2.88; Cl, 27.58; N, 14.53. MS (EI), m/z (Irel (%)): 384
[M]+ (100), 349 [M – Cl]+ (97), 316 [M – MeCN – CO + H]+
(39), 133 [MeC6H4NCO]+ (98). IR, (CHCl3), ν/сm–1: 3392
(NH); 1744 (CO); 1712 (CO); 1592, 1584, 1524. 1H NMR
(CDCl3), δ: 2.42 (s, 3 Н, МеC6H4); 3.05 (s, 3 Н, Ме); 7.15 (d,
2 H, oꢀC6H4, J = 8.0 Hz); 7.36 (d, 2 H, mꢀC6H4, J = 8.0 Hz);
8.88 (br.s, 1 H, NH).
Ethyl 4ꢀaminoꢀ2ꢀ(Nꢀbenzylcarbamoyl)ꢀ6ꢀmethylpyrimidineꢀ
5ꢀcarboxylate (5). A mixture of pyrimidine 3а (0.1 g, 0.34 mmol)
and benzylamine (0.04 mL, 0.4 mmol) in toluene (5 mL)
was refluxed for 6 h. The precipitate that formed was idenꢀ
tified by 1H NMR spectrum as benzylamine hydrochloride,
m.p. 261—263 °С, and was filtered off. The filtrate was conꢀ
centrated in vacuo, the residue was recrystallized from EtOH.
White crystalline compound 5 well soluble in chloroform and
acetone was obtained in a yield of 0.02 g (19%), m.p. 213—215 °С.
Found (%): C, 61.11; H, 5.88; N, 17.39. C16H18N4O3. Calcuꢀ
lated (%): C, 61.14; H, 5.77; N, 17.82. MS (EI), m/z (Irel (%)):
314 [M]+ (42), 286 [M – CO]+ (13), 269 [M – OEt]+ (15),
181 [M – PhCH2NCO]+ (86), 107 [PhCH2NH2]+ (63), 106
[PhCH2NH]+ (100), 91 [PhCH2]+ (52). IR, (KBr), ν/сm–1
:
3424 (NH); 3368 (NH); 3240, 3192, 1700 (CO); 1680 (CO);
1612, 1516. 1H NMR (CDCl3), δ: 1.42 (t, 3 H, MeCH2, J = 7.1 Hz);
2.68 (s, 3 Н, Ме); 4.40 (q, 2 H, CH2Me, J = 7.1 Hz); 4.66 (d,
2 H, CH2Ph, J = 5.5 Hz); 7.38 (m, 5 H, Ph); 8.35 (br.s, 1 H, NH).
Ethyl 4ꢀ(Nꢀarylureido)ꢀ6ꢀmethylꢀ2ꢀtrichloromethylpyrimiꢀ
dineꢀ5ꢀcarboxylates (6a,b). A mixture of pyrimidine 3а (0.3 g,
1 mmol) and phenyl isocyanate (0.4 mL, 3.7 mmol) or pꢀtolyl
isocyanates (0.4 mL, 3.2 mmol) in dry toluene (2 mL) was
refluxed for 7 h, then it was cooled to 20 °С, the precipitate that
formed was filtered off and washed with petroleum ether. Thus,
compounds 6a,b were obtained.
Ethyl 6ꢀmethylꢀ4ꢀ(Nꢀphenylureido)ꢀ2ꢀtrichloromethylpyrimiꢀ
dineꢀ5ꢀcarboxylate (6a), yield 0.36 g (85%), m.p. 204—206 °С.
Found (%): С, 46.24; Н, 3.64; Cl, 25.31; N, 13.41. C16H15Cl3N4O3.
Calculated (%): C, 46.01; H, 3.62; Cl, 25.46; N, 13.41.
MS (EI), m/z (Irel (%)): 416 [M]+ (9), 297 [M – PhNCO]+
(13), 262 [M – PhNCO – Cl]+ (30), 225 [M – PhNCO – C2H4
– CO2]+ (29), 217 [M – PhNCO – Cl – OEt]+ (43), 119
[PhNCO]+ (100), 91 [PhN]+ (94). IR, (CHCl3), ν/сm–1: 3248
(NH); 1692 (CO); 1588, 1536. IR, (KBr), ν/сm–1: 3224 (NH);
1712 (CO); 1676 (CO); 1604, 1556, 1536. 1H NMR (CDCl3), δ:
1.50 (t, 3 H, MeCH2, J = 7.0 Hz); 2.88 (s, 3 Н, Ме), 4.55 (q,
2 H, CH2, J = 7.0 Hz); 7.15 (t, 1 H, pꢀPh, J = 8.0 Hz); 7.38 (t,
2 H, mꢀPh, J = 8.0 Hz); 7.62 (d, 2 H, oꢀPh, J = 8.0 Hz); 10.19
(br.s, 1 H, NH); 11.29 (br.s, 1 H, NHPh). 13C NMR (CDCl3),
δ: 14.10 (MeCH2); 26.73 (Me); 62.99 (CH2); 95.80 (CCl3);
107.03 (C(5)); 120.19 (oꢀPh); 124.17 (pꢀPh); 129.05 (mꢀPh);
137.61 (ipsoꢀPh); 150.26 (CON); 158.39 (C(4)); 163. 08 (C(2));
165.63 (CO2Et); 171.61 (C(6)). The assignment of the signals in
the 13C NMR spectrum was made based on correlation peaks
in the 2D HMBC spectrum.
The work was carried out with the financial support
of the Russian Academy of Sciences (Basic Research
program No. 18 of the RAS Presidium “Development
of methods of chemical synthesis and design of new
materials”).
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Ethyl 6ꢀmethylꢀ4ꢀ[Nꢀ(4ꢀtolyl)ureido]ꢀ2ꢀtrichloromethylpyriꢀ
midineꢀ5ꢀcarboxylate (6b), yield 0.28 g (63%), m.p. 176—178 °С.
Found (%): С, 47.32; Н, 4.03; Cl, 24.72; N, 12.95. C17H17Cl3N4O3.
Calculated (%): C, 47.30; H, 3.97; Cl, 24.62; N, 12.98. MS
(EI), m/z (Irel (%)): 430 [M]+ (3), 297 [M – MeC6H4NCO]+
(6), 225 [M – MeC6H4NCO – C2H4 – CO2]+ (34), 217
[M – MeC6H4NCO – Cl – OEt]+ (36), 133 [MeC6H4NCO]+
(87), 78 (100). IR, (KBr), ν/сm–1: 3232 (NH), 1712 (CO), 1680
1
(CO), 1576, 1528. H NMR (CDCl3), δ: 1.49 (t, 3 H, MeCH2,
J = 7.0 Hz); 2.35 (s, 3 Н, МеC6H4); 2.87 (s, 3 Н, Ме); 4.54 (q,
2 H, CH2, J = 7.0 Hz); 7.18 (d, 2 H, mꢀPh, J = 8.0 Hz); 7.50
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1 H, NHC6H4).
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Received December 4, 2008;
in revised form January 27, 2009