Synthesis of furyl-, furylvinyl-, thienyl-, pyrrolinylquinazolines and isoindolo[2,1-a]quinazolines

Article abstract of DOI:10.1007/s11172-015-1016-1

A method for the synthesis of hydrogenated furyl-, furylvinyl-, thienyl-, and pyrrolinyl-substituted quinazolin-4-ones was developed. A possibility of the reaction of 2-furylquinazolines with maleic anhydride was demonstrated. A number of quinazolines obtained were subjected to a primary bioscreening on inhibition of acetylcholinesterase.

Full text of DOI:10.1007/s11172-015-1016-1

Russian Chemical Bulletin, International Edition, Vol. 64, No. 6, pp. 1345—1353, June, 2015
1345
Synthesis of furylꢀ, furylvinylꢀ, thienylꢀ, pyrrolinylquinazolines
and isoindolo[2,1ꢀa]quinazolines
V. P. Zaytsev,a,b E. L. Revutskaya,a M. G. Kuz´menko,a R. A. Novikov,c F. I. Zubkov,a E. A. Sorokina,a
E. V. Nikitina,a F. A. A. Toze,d and A. V. Varlamova
aPeoples´ Friendship University of Russia,
6 ul. MiklukhoꢀMaklaya, 117198 Moscow, Russian Federation.
Fax: +7 (495) 955 0779. Eꢀmail: vzaitsev@sci.pfu.edu.ru
bShared Research and Educational Center of PhysicoꢀChemical Studies of New Materials,
Substances, and Catalytic Systems,
3 ul. Ordzhonikidze, 115419 Moscow, Russian Federation.
Fax: +7 (495) 952 2644. Eꢀmail: ckp_fhi@sci.pfu.edu.ru
cV. A. Engel´gardt Institute of Molecular Biology, Russian Academy of Sciences,
32 ul. Vavilova, 119991 Moscow, Russian Federation.
Eꢀmail: novikovfff@bk.ru
dDepartment of Chemistry, University of Douala, Faculty of Sciences,
PO Box 24157, Douala, Cameroon
A method for the synthesis of hydrogenated furylꢀ, furylvinylꢀ, thienylꢀ, and pyrrolinylꢀ
substituted quinazolinꢀ4ꢀones was developed. A possibility of the reaction of 2ꢀfurylquinazoꢀ
lines with maleic anhydride was demonstrated. A number of quinazolines obtained were subꢀ
jected to a primary bioscreening on inhibition of acetylcholinesterase.
Key words: anthranilamide, 2ꢀfurylquinazolinꢀ4ꢀones, isoindolo[2,1ꢀa]quinazolines, intraꢀ
molecular [2+4] cycloaddition, Diels—Alder reaction, inhibition of acetylcholinesterase.
Fused 3a,6ꢀepoxyisoindolone are of interest as availꢀ
able starting compounds for the construction of polycyclic
structures via the epoxy bridge cleavage upon treatment
with both electrophilic and nucleophilic agents.1—7
During the last years, we have been developing a genꢀ
eral strategy for the synthesis of epoxyisoindoles fused with
a heterocyclic ring based on the [2+4] cycloaddition reacꢀ
tion of ꢀfurylꢀsubstituted azaheterocycles with anhydrides
and halides of ,ꢀunsaturated acids. Earlier, we have sugꢀ
gested a preparative synthesis of epoxyisoindoles fused with
the piperidine, quinoline, isoquinoline, oxazine, thiazine,
oxazole, and thiazole fragments.2,3,6—12 In the present
work, we report a method for the synthesis of 2ꢀheteroꢀ
arylquinazolinꢀ4ꢀones, a possible precursors of isoindoloꢀ
quinazolines.
above required a convenient method for the synthesis of
2ꢀfurylꢀsubstituted quinazolines to be developed.
Isoindolo[2,1ꢀа]quinazoline
Luotonin А
The carbon skeletons of azaisoindolo[1,2ꢀb]quinꢀ
azoline and indolo[2,1ꢀb]quinazoline constitute a frameꢀ
work of alkaloids Luotonin A, Luotonin B, and Tryptanꢀ
thrine.13—24 Isoindolo[2,1ꢀa]quinazolines structurally simꢀ
ilar to alkaloids exhibit a wide range of biological activity:
inhibit the TNFꢀ protein, possess sedative, analgesic,
and hypotensive activity.25—28 In the framework of
a general approach to the synthesis of fused epoxyisoinꢀ
doles,2,3,6—12 the preparation of heterocycles indicated
Luotonin B
Tryptanthrine
The condensation of anthranilic acid amides with alꢀ
dehydes described in the works29—33 is the most conveꢀ
nient approach to 2ꢀsubstituted quinazolines. However,
furylꢀ, thienylꢀ, and pyrrolylcarboxaldehydes and furyl keꢀ
tones were not virtually used in these transformations. One
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1345—1353, June, 2015.
1066ꢀ5285/15/6406ꢀ1345 © 2015 Springer Science+Business Media, Inc.

1346
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 6, June, 2015
Zaytsev et al.
Scheme 1
R = H (2a), Me (2b), NO2 (2c), Br (2d, 4a), I (2e, 4b)
of the goals of the present work is the studies of these
carbonyl compounds in the synthesis of 2ꢀhetarylquinazoꢀ
lines and optimization of this process.
The condensation of anthranilamide 1 with 5ꢀmethylꢀ,
5ꢀnitroꢀ, 5ꢀbromoꢀ, and 5ꢀiodofurancarboxaldehydes in
EtOH at room temperature gave 2ꢀfurylquinazolinꢀ4ꢀones 2
in high yields (Scheme 1).
The use in this reaction of CH2Cl2 instead of EtOH
made it possible to obtain quinazolinꢀ4ꢀone (2a) in 71%
yield. In contrast to the data reported in the literature,29—33
compound 2a was formed without assistance of a catalyst
at room temperature. The condensation of compound 1
with 5ꢀhaloꢀsubstituted furancarboxaldehydes was accomꢀ
panied by a gradual oxidation of the tetrahydropyrimidine
fragment, that led to the formation of the mixtures of 2d
with 4a and 2e with 4b in about an equal ratios. Under
argon, the yields of quinazolines 2d,e were 83 and 93%,
respectively.
The condensation of anthranilamide 1 with 2ꢀacetylꢀ
furan in the presence of concentrated HCl gave 2ꢀ(2ꢀfurꢀ
yl)ꢀ2ꢀmethylquinazolinꢀ4ꢀone 5 (Scheme 2). All the physꢀ
icochemical characteristics of the latter are similar to those
described earlier32 (no NMR or mass spectral data were
reported in the published work). Furylacrolein reacted with
anthranilamide 1 to give 2ꢀfurylvinyl substituted quinazoliꢀ
none 6 with transꢀarrangement of substituents at the double
bond, that follows from the spinꢀspin coupling constant
value of the CH=CH protons (J = 15.8 Hz).
The reaction of anthranilamide 1 with furfural in EtOH
led to [(5ꢀoxocyclopentꢀ3ꢀenꢀ1,2ꢀdiyl)di(imino)]dibenzꢀ
amide 3 in 91% yield instead of the target quinazoline 2a
(see Scheme 1). Apparently, after the initial formation of
azomethine, a nucleophilic attack by the nitrogen atom of
the second anthranilamide molecule at ꢀposition of the
furan ring with subsequent recyclization takes place.
The structure of compound 3 was confirmed by analoꢀ
gy with the works34—37 and based on 2D COSY, TOCSY,
1
NOESY, HSQC, and HMBC NMR spectra on H, 13C,
and 15N nuclei. The spatial transꢀarrangement of substituꢀ
ents in cyclopentenone 3 was determined using the 2D
NOESY NMR spectra, which exhibit characteristic strong
crossꢀpeaks between the spatially close protons
(C(1)NHAr—H(2); C(2)NHAr—H(1); C(2)NHAr—H(3)).
The NOE crossꢀpeaks between H(1) and H(2) atoms
turned out to be weak because of their transꢀposition
(3J1,2 = 3.2 Hz).
Secondary anthranilamides 7a—g were used for the
synthesis of quinazolines substituted at N(3) nitrogen
atom, which, in turn, were synthesized based on isatoic
anhydride and primary amines according to the described
Scheme 2

Synthesis of substituted quinazolinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 6, June, 2015
1347
procedure.38 Anthranilamides 7a—g were treated with furꢀ
fural, 5ꢀmethylꢀ and 5ꢀphenylfurfural, furylacrolein, thiꢀ
enylꢀ, benzothienylꢀ, pyrrolꢀ, and Nꢀtosylpyrrolꢀ2ꢀcarbꢀ
oxaldehydes at room temperature in the presence of an acid
catalyst to be converted to 3ꢀsubstituted 2ꢀfurylꢀ,
2ꢀthienylꢀ and 2ꢀpyrrolyl substituted quinazolines 8a—o
(Scheme 3).
HCl in MeCN or EtOH), the yield of the target 8b was not
higher than 30%.
Taking synthesis of quinazoline 8b as an example, we
also showed a possibility of a oneꢀpot approach (see Exꢀ
perimental), in this case the yield of the target product did
not considerably change as compared to the twoꢀstep verꢀ
sion. The physicochemical characteristics of compounds
8a—c are completely the same as those data reported in
the work.39 The 1H NMR spectrum of 3ꢀsubstituted
quinazolines 8d—o, apart from the characteristic signals
for the NH and H(2) protons in the region of H 4.42—4.71
and H 4.99—5.98, respectively, also exhibit signals for the
chemically nonequivalent protons of the CH2 group
as an ABꢀsystem with the spinꢀspin coupling constant
2JA,B = 15.1—15.8 Hz (except 8e,f). In the 13C NMR
spectra, the most characteristic is the chemical shift for
C(2) carbon atom in the region of C 64.4—67.2.
Scheme 3
Some of the synthesized quinazolines were subjected
to a preliminary bioscreening in vitro for the inhibition of
acetylcholinesterase (AChE).40 It was found that the inꢀ
hibiting activity of quinazolines 2—6, 8 and cyclopenꢀ
tanone 3 ranged from low to moderate (%): 33 (2a), 14 (2b),
24 (2d), 7 (2e), 22 (3), 18 (4b), 9 (5), 33 (6), 15 (8b),
34 (8d), 12 (8e), 18 (8f), 14 (8g), 30 (8h), 12 (8j), 22 (8k),
5 (8l), 18 (8m), 19 (8o).
i. MeCN, 25 C, TsOH.
Furylꢀsubstituted quinazolines 2a,b with maleic anhyꢀ
dride in CHCl3 at 20 C undergo an exoꢀ[2+4] cycloadꢀ
dition to form a mixture of isomers of epoxyisoindolo[2,1ꢀa]ꢀ
quinazolineꢀ10ꢀcarboxylic acid 9a,b differing in the arꢀ
rangement of the epoxy bridge and H(6a) proton (the ratio
of isomers is given in Experimental). The oneꢀpot version
of this reaction without isolation of 2ꢀfurylquinazoline 2a
gave a higher yield of epoxyisoindoloquinazolinecarboxylic
acid 9a (94%), with the ratio of isomers in the mixture
remaining the same (Scheme 4). Carrying out the reaction
in refluxing CHCl3 or 1,2ꢀdichloroethane almost have no
R = 2ꢀfuryl (7a, 8a), Ph (7b, 8b,h,j—o), Me (7c, 8c),
vinyl (7d, 8d,i), Bn (7e, 8e), 3,4ꢀ(MeO)2C6H3CH2 (7f, 8f),
2ꢀthienyl (7g, 8g)
R´ = 2ꢀfuryl (8a—g), 5ꢀMeꢀ2ꢀfuryl (8h,i), 5ꢀPhꢀ2ꢀfuryl (8j),
(E)ꢀ2ꢀ(2ꢀfuryl)vinyl (8k), 2ꢀthienyl (8l),
2ꢀbenzo[b]thienyl (8m), 2ꢀpyrrolinyl (8n), NꢀTsꢀ2ꢀpyrrolinyl (8o)
The reaction of amide 7b with furfural has been chosen
as a model for the selection of optimal conditions. The
most efficient catalyst was TsOH in MeCN: the yield of
quinazoline 8b under these conditions was as high as 79%.
In the presence of other catalysts (AcOH or concentrated
Scheme 4
R = H (9a), Me (9b)

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Zaytsev et al.
(1.26 g, 38%) and quinazoline 2e (1.71 g, 44%), quinazoline 4b
(1.46 g, 38%), respectively. The mixed probe of the samples
obtained by methods A and B showed no temperature depression.
2ꢀ(5ꢀMethylꢀ2ꢀfuryl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀone (2b).
The yield was 8.4 g (68%). A colorless powder, m.p. 177—178 C
effect on the ratio of isomers A/B (55 : 45). The stereꢀ
ochemistry of the isomeric adducts 9a,b was established
based on the data in the work.39 In the 1H NMR spectra of
these adducts, the signal for H(1) proton in transꢀisomers A
is ~0.2 ppm more downfield shifted as compared to the
corresponding proton in cisꢀisomers B.
(EtOH—DMF), Rf 0.64 (EtOAc—hexane, 4 : 1). IR, /cm–1
:
1
3288 (N—H), 1646 (NC=O). H NMR (400 MHz, CDCl3), :
2.27 (d, 3 H, Me, J = 0.8 Hz); 4.56 (br.s, 1 H, NH); 5.85 (t, 1 H,
H(2), J = 1.8 Hz); 5.91 (dq, 1 H, HFur(4´), J = 0.8 Hz, J = 3.2 Hz);
6.09 (br.s, 1 H, NH); 6.29 (d, 1 H, HFur(3´), J = 3.2 Hz); 6.68
(dd, 1 H, H(8), J = 0.8 Hz, J = 8.0 Hz); 6.87 (ddd, 1 H, H(6),
J = 0.8 Hz, J = 7.5 Hz, J = 8.0 Hz); 7.31 (ddd, 1 H, H(7),
J = 1.4 Hz, J = 7.5 Hz, J = 8.0 Hz); 7.90 (dd, 1 H, H(5),
J = 1.4 Hz, J = 8.0 Hz). 13C NMR (100 MHz, DMSOꢀd6),
: 13.3 (Me); 60.3 (C(2)); 106.3, 108.1, 114.5, 114.9, 117.1, 127.2,
133.2 (Ar); 147.2, 151.4, 152.2 (C(8a), CFur´(2´), CFur´(5´)); 163.3
(C=O). MS, m/z (Irel (%)): 228 [M]+ (83), 213 (60), 185 (68),
147 (75), 120 (100), 109 (52), 92 (66), 81 (36), 65 (71), 59 (52),
55 (26), 43 (47). Found (%): C, 68.59; H, 5.11; N, 12.56.
C13H12N2O2. Calculated (%): C, 68.41; H, 5.30; N, 12.27.
2ꢀ(2ꢀFurylꢀ5ꢀnitro)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀone (2c).
The yield was 12.4 g (95%). A powder, m.p. 168—169 C
In conclusion, we synthesized the libraries of 2ꢀheteroꢀ
arylꢀsubstituted quinazolines, carried out their bioscreenꢀ
ing with regard to the inhibition of acetylcholinesterase,
and showed a principal possibility of the transformation of
2ꢀfurylquinazolines to epoxyisoindoloquinazolines.
Experimental
IR spectra were recorded on a Infralyum FTꢀ801 Fourierꢀ
transform spectrometer in KBr pellets. 1H NMR spectra were
recorded on Bruker AMXꢀ400 (400 MHz) or JEOL
JNMꢀECA600 (600 MHz) spectrometers for ~3% solutions in
CDCl3 or DMSOꢀd6, using residual signals of the solvent as
a reference ( 7.26 for CHCl3 and 2.49 for DMSOꢀd6).
13C NMR spectra were recorded on Bruker Avance 600 (150 MHz)
or Bruker AMXꢀ400 (100 MHz) spectrometers, the central sigꢀ
nals of the CDCl3 triplet (d 77.4) or the DMSOꢀd6 multiplet
( 40.0) were used as a reference. Mass spectra were obtained on
a Thermo Trace DSQ mass spectrometer (electron ionization
70 eV, temperature of the source of ions 200 C, direct injection)
or a Thermo DSQ II — Focus GC GCꢀMS spectrometer (elecꢀ
tron ionization 70 eV, temperature of the source of ions 200 C,
carrier gas helium, a RTXꢀ5MS column). Elemental analysis
was carried out on a EuroVector EA 3000 CHNSꢀanalyzer. Meltꢀ
ing points of the synthesized compounds were determined on
SMP 10 and SMP 30 instruments (were not corrected). Bioꢀ
(EtOH—DMF), Rf 0.50 (EtOAc—hexane, 4 : 1). IR, /cm–1
:
3294 (N—H), 1668 (NC=O). 1H NMR (400 MHz, DMSOꢀd6),
: 7.30 (br.d, 1 H, H(8), J = 7.5 Hz); 7.40 (br.t, 1 H, H(6),
J = 7.5 Hz); 7.52 (d, 1 H, HFur(3´), J = 3.7 Hz); 7.56 (dt, 1 H, H(7),
J = 1.2 Hz, J = 7.5 Hz); 7.61 (br.s, 1 H, NH); 7.84 (d, 1 H,
HFur(4´), J = 3.7 Hz); 7.88 (dd, 1 H, H(5), J = 1.2 Hz,
J = 7.5 Hz); 8.11 (br.s, 1 H, NH); 8.58 (s, 1 H, H(2)). MS, m/z
(Irel (%)): 259 [M]+ (18), 242 (100), 213 (33), 185 (31), 168 (20),
147 (54), 140 (50), 130 (58), 119 (33), 105 (76), 92 (34), 79 (26),
65 (27), 51 (41), 43 (36). Found (%): C, 55.55; H, 3.68; N, 16.13.
C12H9N3O4. Calculated (%): C, 55.60; H, 3.50; N, 16.21.
2ꢀ(5ꢀBromoꢀ2ꢀfuryl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀone (2d).
The yield was 12.2 g (83%) by method A and 0.94 g (28%) by
method B. Light yellow plates, m.p. 153—154 C (EtOAc—EtOH),
Rf 0.65 (EtOAc—hexane, 2 : 1). IR, /cm–1: 3266 (N—H), 1651
(NC=O). 1H NMR (600 MHz, DMSOꢀd6), : 5.72 (t, 1 H,
H(2), J = 2.8 Hz); 6.26 (d, 1 H, HFur(3´), J = 3.4 Hz); 6.45
(d, 1 H, HFur(4´), J = 3.4 Hz); 6.66 (dt, 1 H, H(6), J = 1.4 Hz,
J = 8.2 Hz); 6.72 (d, 1 H, H(8), J = 7.6 Hz); 7.22 (ddd, 1 H, H(7),
J = 1.4 Hz, J = 7.6 Hz, J = 8.2 Hz); 7.25 (br.s, 1 H, NH); 7.57
(dd, 1 H, H(5), J = 1.4 Hz, J = 8.2 Hz); 8.11 (br.d, 1 H, NH,
J = 2.8 Hz). 13C NMR (100 MHz, DMSOꢀd6), : 60.1 (C(2)); 110.2,
112.3, 114.6, 114.9, 117.5, 120.9, 127.3, 133.3 (Ar); 146.8, 156.6
(C(8a), CFur(2´)); 163.1 (C=O). MS, m/z (Irel (%)): 294 [M]+
(for 81Br) (94), 292 (95), 213 (66), 185 (24), 174 (19), 148 (17),
147 (99), 130 (21), 121 (25), 120 (62), 119 (100), 102 (18), 93 (14),
92 (83), 66 (23), 65 (70), 52 (20), 51 (38), 43 (28). Found (%):
C, 48.98; H, 3.20; N, 9.71. C12H9BrN2O2. Calculated (%): C, 49.17;
H, 3.09; N, 9.56.
screening data were obtained for solutions of quinazolines in
40
DMSO (10–5 mol L–1
)
on Tecan Infinite M1000 Pro multiꢀ
functional plate analyzer. Sorbfil PTSKhꢀAFꢀAꢀUV 254 plates
were used for TLC, visualization was carried out in iodine vaꢀ
pors. Ratios of products in the isomeric mixtures (for 9a,b) were
determined based on the 1H NMR spectra from the ratios of
integral intensities of the signals for similar protons.
Commercially available reactants from Acros Organics and
Alfa Aesar were used without additional purification, solvents
were purified by distillation. Synthesis, spectral and physicoꢀ
chemical characteristics, as well as elemental analysis data for
compounds 2a, 5, and 8a—c were published earlier.32,39,41,42
2ꢀ(5ꢀRꢀ2ꢀFuryl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀones 2b—e
and 2ꢀ(5ꢀRꢀ2ꢀfuryl)quinazolinꢀ4(3H)ꢀones 4a,b (general proceꢀ
dure). A. A corresponding aldehyde (0.05 mol) was added to
a solution of anthranilamide 1 (6.81 g, 0.05 mol) in EtOH (50 mL)
under argon (for 2d,e). The reaction mixture was stirred at room
temperature for 72 h (for 2b), 0.5 h for (2c), 48 h (for 2d), or
5 days (for 2e). The crystals formed were filtered, washed with
Et2O (20 mL), and purified by recrystallization.
B. 5ꢀHalofurfural (11.4 mmol) was added to a solution of
anthranilamide 1 (1.55 g, 11.4 mmol) in EtOH (30 mL). The
reaction mixture was stirred for 48 h (TLC monitoring). The
crystals formed were filtered off and washed with Et2O (20 mL).
The resulting mixture was subjected to chromatography (Al2O3
(4×25 cm), eluent hexane, then EtOAc—hexane 1 : 10, 1 : 5,
1 : 1) to obtain quinazoline 2d (0.94 g, 28%), quinazoline 4a
2ꢀ(2ꢀFurylꢀ5ꢀiodo)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀone (2e).
The yield was 15.8 g (93%) by method A and 1.71 g (44%) by
method B. Brickꢀred fine needles, m.p. 172—173 C (EtOAc—
EtOH), Rf 0.65 (EtOAc—hexane, 1 : 1). IR, /cm–1: 3270 (N—H),
1653 (NC=O). 1H NMR (600 MHz, DMSOꢀd6), : 5.71 (d, 1 H,
H(2), J = 3.4 Hz); 6.15 (dd, 1 H, HFur(3´), J = 0.6 Hz, J = 3.4 Hz);
6.52 (d, 1 H, HFur(4´), J = 3.4 Hz); 6.63 (dt, 1 H, H(6), J = 0.9 Hz,
J = 7.7 Hz); 6.71 (br.d, 1 H, H(8), J = 8.2 Hz); 7.18 (br.s, 1 H,
NH); 7.19 (ddd, 1 H, H(7), J = 1.6 Hz, J = 7.7 Hz, J = 8.2 Hz);
7.57 (dd, 1 H, H(5), J = 1.6 Hz, J = 7.7 Hz); 8.36 (d, 1 H, NH,

Synthesis of substituted quinazolinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 6, June, 2015
1349
J = 3.4 Hz). 13C NMR (100 MHz, DMSOꢀd6), : 60.0 (C(2));
91.4 (CFur(5´)); 110.3, 114.5, 114.9, 117.4, 120.4, 127.3, 133.3
(Ar); 146.9, 159.6 (C(8a), CFur(2´)); 163.1 (C=O). MS, m/z
(Irel (%)): 340 [M]+ (50), 213 (100), 194 (19), 183 (15), 156 (15),
147 (30), 130 (33), 120 (75), 77 (19), 64 (29), 59 (25), 43 (43).
Found (%): C, 42.45; H, 2.51; N, 8.06. C12H9IN2O2. Calculatꢀ
ed (%): C, 42.38; H, 2.67; N, 8.24.
2ꢀ(5ꢀBromoꢀ2ꢀfuryl)quinazolinꢀ4(3H)ꢀone (4a). The yield
was 1.26 g (38%) by method B. Yellow thin threadꢀlike crystals,
m.p. 259—260 C (EtOAc—EtOH), Rf 0.81 (EtOAc—hexane,
1 : 1). IR, /cm–1: 1658 (NC=O). 1H NMR (600 MHz, DMSOꢀd6),
: 6.81 (d, 1 H, HFur(3´), J = 3.4 Hz); 7.45 (t, 1 H, H(6),
J = 7.6 Hz); 7.62 (d, 1 H, HFur(4´), J = 3.4 Hz); 7.68 (d, 1 H,
H(8), J = 7.6 Hz); 7.76 (t, 1 H, H(7), J = 7.6 Hz); 8.08 (d, 1 H,
H(5), J = 7.6 Hz); 8.24 (br.s, 1 H, NH). MS, m/z (Irel (%)):
292 [M]+ (for 81Br) (100), 290 (99), 211 (25), 183 (21), 156 (29),
145 (16), 102 (16), 90 (39), 43 (35), 39 (18). Found (%): C, 49.50;
H, 2.17; N, 9.73. C12H7BrN2O2. Calculated (%): C, 49.51;
H, 2.42; N, 9.62.
2ꢀ(2ꢀFurylꢀ5ꢀiodo)quinazolinꢀ4(3H)ꢀone (4b). The yield was
1.46 g (38%) by method B. Light yellow thin threadꢀlike crystals,
m.p. 265—268 C (EtOAc—EtOH), Rf 0.91 (EtOAc—hexane,
1 : 1). IR, /cm–1: 1656 (NC=O). 1H NMR (600 MHz, DMSOꢀd6),
: 6.93 (d, 1 H, HFur(3´), J = 3.6 Hz); 7.47 (ddd, 1 H, H(6),
J = 0.8 Hz, J = 7.6 Hz, J = 7.9 Hz); 7.54 (d, 1 H, HFur(4´),
J = 3.6 Hz); 7.70 (dd, 1 H, H(8), J = 0.8 Hz, J = 8.2 Hz); 7.79 (ddd,
1 H, H(7), J = 1.5 Hz, J = 7.6 Hz, J = 8.2 Hz); 8.11 (dd, 1 H,
H(5), J = 1.5 Hz, J = 7.9 Hz); 8.27 (s, 1 H, NH). 13C NMR
(100 MHz, DMSOꢀd6), : 98.1 (CFur(5´)); 116.8, 121.2, 122.6,
125.9, 126.5, 127.2, 134.6 (Ar); 142.9, 148.4, 150.8 (C(2), C(8a),
CFur(2´)); 161.4 (C=O). MS, m/z (Irel (%)): 338 [M]+ (100),
211 (42), 183 (33), 130 (15), 102 (24), 90 (22), 64 (23), 59 (17),
43 (40). Found (%): C, 42.44; H, 2.20; N, 8.32. C12H7IN2O2.
Calculated (%): C, 42.63; H, 2.09; N, 8.29.
2,2´ꢀ[[(1RS,2SR)ꢀ5ꢀOxocyclopentꢀ3ꢀenꢀ1,2ꢀdiyl]di(imino)]ꢀ
dibenzamide (3). Furfural (4.14 mL, 0.05 mol) was added to
a solution of anthranilamide 1 (13.62 g, 0.10 mol) in EtOH
(50 mL), and the mixture was stirred at room temperature for 48 h
(TLC monitoring). The crystals formed were filtered and washed
with Et2O (20 mL) to obtain cyclopentenone 3 (14.75 g (84%) as
a colorless powder. M.p. 182—183 C (EtOAc—EtOH), Rf 0.45
(EtOAc). The use of anhydrous EtOH as the solvent increased
the yield of compound 3 to 91%. IR, /cm–1: 1613, 1642, 1666,
1728 (C=O), 3179, 3337, 3395 (N—H). 1H NMR (400 MHz,
DMSOꢀd6), : 4.24 (dd, 1 H, H(1), J = 3.2 Hz, J = 6.5 Hz); 4.75
(br.d, 1 H, H(2), J = 7.8 Hz); 6.45 (dd, 1 H, H(4), J = 1.3 Hz,
was added to a solution of anthranilamide 1 (10.0 g, 0.074 mol)
in EtOH (100 mL), and the mixture was stirred at room temperꢀ
ature for 48 h (TLC monitoring). The crystals formed were filꢀ
tered, washed with Et2O (20 mL), and recrystallized from a mixꢀ
ture of EtOAc—hexane to obtain quinazoline 5 (13.25 g, 73%) as
a colorless powder. Physicochemical characteristics and the IR
spectroscopy data of quinazoline 5 similar to those described in
the work.32 M.p. 226—228 C (cf. Ref. 32: m.p. 221—225 C),
Rf 0.64 (EtOAc—hexane, 3 : 1). 1H NMR (400 MHz, DMSOꢀd6),
: 1.70 (s, 3 H, Me); 6.11 (br.d, 1 H, HFur(3´), J = 3.1 Hz); 6.29
(dd, 1 H, HFur(4´), J = 1.9 Hz, J = 3.1 Hz); 6.63 (t, 1 H, H(6),
J = 7.6 Hz); 6.68 (d, 1 H, H(8), J = 8.1 Hz); 7.21 (ddd, 1 H, H(7),
J = 1.8 Hz, J = 7.6 Hz, J = 8.1 Hz); 7.31 (br.s, 1 H, NH); 7.53
(br.d, 1 H, HFur(5´), J = 1.9 Hz); 7.56 (dd, 1 H, H(5), J = 1.8 Hz,
J = 7.6 Hz); 8.48 (br.s, 1 H, NH). 13C NMR (100 MHz, DMSOꢀd6),
: 27.2 (Me); 66.5 (C(2)); 105.8, 110.0, 114.0, 114.3, 116.9, 127.1,
133.2 (Ar); 142.2 (CFur(5´)); 146.8, 157.9 (C(8a), CFur(2´)); 163.5
(C=O). MS, m/z (Irel (%)): 228 [M]+ (34), 213 (100), 184 (18),
161 (11), 145 (10), 120 (46), 110 (13), 92 (39), 65 (41), 59 (10),
43 (21).
2ꢀ[(E)ꢀ2ꢀ(2ꢀFuryl)vinyl]ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀone
(6). Furylacrolein (0.89 g, 7.0 mmol) was added to a solution of
anthranilamide 1 (1.0 g, 7.4 mmol) in EtOH (30 mL), and the
mixture was stirred at room temperature for 1 month (TLC monꢀ
itoring). The crystals formed were filtered and washed with Et2O
(20 mL) to obtain quinazoline 6 (0.77 g, 43%). Beige fine plates,
m.p. 168—169 C (EtOH), Rf 0.56 (EtOAc—hexane, 2 : 1). IR,
cm–1: 1638 (NC=O), 3253 (N—H). 1H NMR (600 MHz,
DMSOꢀd6), : 5.23 (br.d, 1 H, H(2), J = 6.2 Hz); 6.09 (dd, 1 H,
C(2)CH=CH, J = 6.2 Hz, J = 15.8 Hz); 6.45 (dd, 1 H, HFur(4´),
J = 1.9 Hz, J = 3.4 Hz); 6.47 (d, 1 H, HFur(3´), J = 3.4 Hz); 6.49
(d, 1 H, C(2)CH=CH, J = 15.8 Hz); 6.64 (br.t, 1 H, H(6),
J = 7.6 Hz); 6.70 (d, 1 H, H(8), J = 7.6 Hz); 6.86 (s, 1 H, NH);
7.21 (dt, 1 H, H(7), J = 1.4 Hz, J = 7.6 Hz); 7.57 (dd, 1 H, H(5),
J = 1.4 Hz, J = 7.6 Hz); 7.59 (d, 1 H, HFur(5´), J = 1.7 Hz); 8.13
(s, 1 H, NH). 13C NMR (100 MHz, DMSOꢀd6), : 65.0 (C(2));
109.6, 111.7, 114.6, 114.9, 117.2, 119.9, 126.7, 127.3, 133.2 (Ar,
C(2)CH=CH, C(2)CH=CH); 143.1 (CFur(5´)); 147.6, 151.1
(C(8a), CFur(2´)); 163.4 (C=O). MS, m/z (Irel (%)): 240 [M]+
(50), 211 (22), 197 (14), 184 (17), 160 (20), 147 (36), 130 (17),
120 (100), 92 (50), 81 (23), 65 (36), 59 (29), 52 (17), 51 (25), 43
(55). Found (%): C, 69.87; H, 4.89; N, 11.48. C14H12N2O2.
Calculated (%): C, 69.99; H, 5.03; N, 11.66.
NꢀAlkylꢀ2ꢀaminobenzamides 7a—g (general procedure).
A corresponding amine (20.2 mmol) was added to a solution of
isatoic anhydride (3.0 g, 18.4 mmol) in anhydrous MeCN
(60 mL), and the mixture was stirred for 2 h at room temperaꢀ
ture, then 4 h at 50 C. The solvent was evaporated to obtain
amides 7a (58%), 7b (86%), 7c (97%), 7d (73%), 7e (80%), 7f
(81%), and 7g (55%) as colorless crystals. Physicochemical charꢀ
acteristics and spectral data of amides 7a—e are identical to
those described in the work.38
J = 6.5 Hz); 6.55, 6.59 (both t, 1 H each, HC H (5´), J = 7.8 Hz);
6
6.68, 6.86 (both d, 1 H each, HC H (3´), J = 74.8 Hz); 7.11, 7.19
(both t, 1 H each, HC H (4´), J =67.48 Hz); 7.23 (br.s, 2 H, NH2);
6
7.60, 7.63 (both dd, 1 H4each, HC H (6´), J = 1.3 Hz, J = 7.8 Hz);
6
4
7.69 (dd, 1 H, H(3), J = 1.3 Hz, J = 6.5 Hz); 7.86 (br.s, 2 H,
NH2); 8.65 (d, 1 H, NH, J = 6.5 Hz); 8.68 (d, 1 H, NH, J = 7.8 Hz).
13C NMR (100 MHz, DMSOꢀd6), : 59.4 (C(2)); 64.9 (C(1));
112.1, 112.4 (CC H (3´)); 114.8, 114.9 (CC H (1´)); 115.1, 115.2
2ꢀAminoꢀNꢀ[2ꢀ(3,4ꢀdimethoxyphenyl)ethyl]benzamide (7f).
The yield was 4.47 g (81%). A colorless powder, m.p. 103—104 C
6
6
(CC H (5´)); 129.0,4129.2 (CC H (6´)); 132.2 (4C(4)); 132.3, 132.6
(hexane—EtOAc), Rf 0.56 (EtOAc—hexane, 1 : 1.5). IR, cm–1
:
(CC H4(4´)); 148.4, 149.0 (CC H4(2´)); 161.0 (C(3)); 171.4, 171.5
1636, 1517 (NC=O), 3328, 3416 (N—H). 1H NMR (400 MHz,
CDCl3), : 2.90 (t, 2 H, NHCH2CH2, J = 6.9 Hz); 3.68 (q, 2 H,
NHCH2CH2, J = 6.9 Hz); 3.88, 3.90 (both s, 3 H each, OMe);
6.13 (br.s, 1 H, NH); 6.69 (t, 1 H, H(5), J = 7.3 Hz); 6.78—6.87
(m, 3 H, Ar); 7.21—7.26 (m, 2 H, Ar); 7.29 (d, 1 H, Ar, J = 2.3 Hz).
13C NMR (150 MHz, CDCl3), : 35.3 (NCH2CH2); 41.0
(NCH2CH2); 55.9, 56.0 (both OMe); 111.6, 112.1, 116.3, 116.7,
6
6
(CONH2); 203.4 (C=O). MS, 4m/z (Irel (%)): 215 [M – 135]+
(21), 197 (8), 185 (10), 169 (12), 136 (100), 119 (82), 92 (66), 65 (48),
43 (29). Found (%): C, 65.37; H, 5.36; N, 16.10. C19H18N4O3.
Calculated (%): C, 65.13; H, 5.18; N, 15.99.
6
4
6
2ꢀ(2ꢀFuryl)ꢀ2ꢀmethylꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀone (5).
2ꢀAcetylfuran (8.1 g, 0.074 mol) and concentrated HCl (1 mL)

1350
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 6, June, 2015
Zaytsev et al.
117.4, 120.8, 127.1, 131.6, 132.3, 147.8, 148.7, 149.1 (Ar); 169.4
(NC=O). MS, m/z (Irel (%)): 300 [M]+ (6), 164 (46), 151 (56),
120 (100), 119 (24), 92 (42), 65 (24). Found (%): C, 68.10;
H, 6.82; N, 9.12. C17H20N2O3. Calculated (%): C, 67.98;
H, 6.71; N, 9.33.
1624 (NC=O), 3297 (N—H). 1H NMR (400 MHz, CDCl3),
: 2.86—3.01 (m, 2 H, NCH2CH2); 3.09—3.16 (m, 1 H,
NCH2CH2); 4.27—4.33 (m, 1 H, NCH2CH2); 5.45 (s, 1 H,
H(2)); 6.16 (br.d, 1 H, HFur(3´), J = 3.4 Hz); 6.22 (dd, 1 H,
HFur(4´), J = 1.8 Hz, J = 3.2 Hz); 6.60 (d, 1 H, H(8), J = 7.8 Hz);
6.86 (t, 1 H, H(7), J = 7.8 Hz); 7.21—7.30 (m, 7 H, H(6),
HFur(5´), C6H5); 7.93 (dd, 1 H, H(5), J = 1.4 Hz, J = 7.8 Hz).
13C NMR (100 MHz, CDCl3), : 34.8 (NCH2CH2); 47.6
(NCH2CH2); 66.4 (C(2)), 108.4, 110.5, 114.9, 116.9, 119.8,
126.5, 128.5, 128.6, 129.0, 133.4, 139.1 (Ar); 143.0 (CFur(5´));
145.1 (C(8a)); 152.3 (CFur(2´)); 162.9 (C=O). MS, m/z (Irel (%)):
318 [M]+ (18), 213 (34), 198 (100), 170 (14), 115 (20), 104 (16),
91 (24), 77 (18), 65 (10), 39 (10). Found (%): C, 75.20; H, 5.54;
N, 8.99. C20H18N2O2. Calculated (%): C, 75.45; H, 5.70;
N, 8.80.
2ꢀAminoꢀNꢀ(2ꢀthienylmethyl)benzamide (7g). The yield was
2.35 g (55%). A colorless powder, m.p. 109—110 C (hexane—
EtOAc), Rf 0.55 (EtOAc—hexane, 1 : 1.5). IR, cm–1: 1521,
1580, 1629 (NC=O), 3352, 3473 (N—H). 1H NMR (600 MHz,
CDCl3), : 4.69 (d, 2 H, NHCH2, J = 5.5 Hz); 5.41 (s, 2 H,
NH2); 6.33 (s, 1 H, NH); 6.56 (ddd, 1 H, H(5), J = 1.4 Hz,
J = 7.3 Hz, J = 8.2 Hz); 6.61 (d, 1 H, H(3), J = 8.2 Hz); 6.90 (dd,
1 H, HThien(4´), J = 3.4 Hz, J = 5.2 Hz); 6.96 (br.d, 1 H,
HThien(3´), J = 3.4 Hz); 7.14 (dt, 1 H, H(4), J = 1.4 Hz, J = 8.2 Hz);
7.18 (dd, 1 H, HThien(5´), J = 1.4 Hz, J = 5.2 Hz); 7.24 (dd, 1 H,
H(6), J = 1.4 Hz, J = 7.6 Hz). 13C NMR (150 MHz, CDCl3),
: 38.5 (NCH2); 115.7 (C(1)); 116.7, 117.4, 125.3, 126.1, 127.0,
127.3, 132.6 (C(3), C(4), C(5), C(6) Ar, CThien(3), CThien(4),
CThien(5´)); 141.2, 148.9 (C(2) Ar, CThien(2´)); 169.1 (NCO).
MS, m/z (Irel (%)): 232 [M]+ (24), 120 (34), 112 (100), 97 (38),
92 (22), 65 (20). Found (%): C, 62.17; H, 5.43; N, 11.87; S, 13.93.
C12H12N2OS. Calculated (%): C, 62.04; H, 5.21; N, 12.06;
S, 13.80.
Synthesis of 2ꢀ(2ꢀfuryl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀones
8a—o (general procedure). A corresponding aldehyde (2.42 mmol)
and TsOH (0.21 g, 1.1 mmol) were added to a solution of
2ꢀaminobenzamide 7a—g (2.2 mmol) in MeCN (30 mL), and
the mixture was stirred at room temperature for 1—4 h (TLC
monitoring), poured into water (50 mL), alkalized with an aqueꢀ
ous solution of NaHCO3, and extracted with CHCl3 (3×20 mL).
The extract was dried with anhydrous MgSO4. The residue after
removal of the solvent was purified by recrystallization from
a mixture of EtOAc—hexane. Quinazolines 8a (63%), 8b (79%),
and 8c (38%) were obtained earlier, their physicochemical charꢀ
acteristics and spectral data are completely agree with those deꢀ
scribed in the work.39
3ꢀAllylꢀ2ꢀ(2ꢀfuryl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀone (8d).
The yield was 0.47 g (85%). Colorless needles, m.p. 119—120 C,
Rf 0.40 (EtOAc—hexane, 1 : 3). IR, cm–1: 1626 (NC=O), 3245
(N—H). 1H NMR (400 MHz, CDCl3), : 3.47 (dd, 1 H, J = 7.5 Hz,
J = 15.6 Hz) and 4.94 (ddd, 1 H, CH2CH=CH2, J = 1.8 Hz,
J = 4.5 Hz, J = 15.6 Hz); 4.71 (br.s, 1 H, NH); 5.23 (dd, 1 H,
J = 1.2 Hz, J = 10.0 Hz) and 5.30 (ddd, 1 H, CH2CH=CH2,
J = 1.2 Hz, J = 1.8 Hz, J = 17.5 Hz); 5.71 (s, 1 H, H(2)); 5.85
(dddd, 1 H, CH2CH=CH2, J = 4.5 Hz, J = 7.5 Hz, J = 10.0 Hz,
J = 17.5 Hz); 6.18 (d, 1 H, HFur(3´), J = 3.7 Hz); 6.24 (dd, 1 H,
HFur(4´), J = 1.8 Hz, J = 3.7 Hz); 6.62 (d, 1 H, H(8), J = 8.1 Hz);
6.86 (t, 1 H, H(6), J = 7.5 Hz); 7.26 (ddd, 1 H, H(7), J = 1.2 Hz,
J = 7.5 Hz, J = 8.1 Hz); 7.31 (br.d, 1 H, HFur(5´), J = 1.8 Hz);
7.94 (dd, 1 H, H(5), J = 1.2 Hz, J = 7.5 Hz). 13C NMR
(150 MHz, CDCl3), : 46.6 (CH2CH=CH2); 64.4 (C(2)); 108.1,
110.4, 114.9 (Ar); 116.3 (C(4a)); 118.0, 119.3, 128.5, 132.7, 133.6
(Ar, CH2CH=CH2, CH2CH=CH2); 142.9 (CFur(5´)); 145.5
(C(8a)); 152.4 (CFur(2´)); 162.9 (C=O). MS, m/z (Irel (%)): 254
[M]+ (56), 237 (42), 213 (55), 187 (45), 170 (100), 147 (45), 119
(98), 92 (45), 77 (24), 64 (15), 41 (46). Found (%): C, 71.04;
H, 5.54; N, 11.18. C15H14N2O2. Calculated (%): C, 70.85;
H, 5.55; N, 11.02.
3ꢀ[2ꢀ(3,4ꢀDimethoxyphenyl)ethyl]ꢀ2ꢀ(2ꢀfuryl)ꢀ2,3ꢀdihydroꢀ
quinazolinꢀ4(1H)ꢀone (8f). The yield was 0.32 g (39%). Colorless
fine needles, m.p. 112 C, Rf 0.57 (EtOAc—hexane, 1 : 2). IR,
/cm–1: 1651 (NC=O), 3344 (N—H). 1H NMR (400 MHz,
CDCl3), : 2.81—2.96 (m, 2 H, NCH2CH2); 3.02—3.09 (m, 1 H,
NCH2CH2); 3.80, 3.85 (both s, 3 H each, OMe); 4.28—4.34
(m, 1 H, NCH2CH2); 4.59 (br.d, 1 H, NH, J = 2.1 Hz); 5.37 (d, 1 H,
H(2), J = 2.1 Hz); 6.15 (dd, 1 H, HFur(3´), J = 0.9 Hz, J = 3.2 Hz);
6.22 (dd, 1 H, HFur(4´), J = 1.8 Hz, J = 3.2 Hz); 6.58 (d, 1 H,
H(8), J = 8.2 Hz); 6.75—6.81 (m, 3 H, C6H3); 6.85 (dt, 1 H,
H(6), J = 0.9 Hz, J = 8.2 Hz); 7.24 (dt, 1 H, H(7), J = 1.6 Hz,
J = 8.2 Hz); 7.29 (dd, 1 H, HFur(5´), J = 0.9 Hz, J = 1.8 Hz); 7.93
(dd, 1 H, H(5), J = 1.6 Hz, J = 7.8 Hz). 13C NMR (100 MHz,
CDCl3), : 34.4 (NCH2CH2); 47.8 (NCH2CH2); 55.9, 56.0 (both
OMe); 66.4 (C(2)); 108.3, 110.4, 111.4, 112.4, 114.8, 116.7,
119.7, 120.8, 128.4, 131.8, 133.4 (Ar); 142.9 (CFur(5´)); 145.2
(C(8a)); 147.7, 148.9 (both COMe); 152.4 (CFur(2´)); 162.9
(C=O). MS, m/z (Irel (%)): 378 [M]+ (5), 281 (19), 213 (35), 207
(100), 198 (53), 197 (17), 164 (88), 151 (24), 133 (13), 119 (20),
115 (16), 77 (13), 73 (14), 44 (47). Found (%): C, 70.10; H, 5.77;
N, 7.45. C22H22N2O4. Calculated (%): C, 69.83; H, 5.86; N, 7.40.
2ꢀ(2ꢀFuryl)ꢀ3ꢀ(2ꢀthienylmethyl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀ
one (8g). The yield was 0.34 g (50%). Colorless plates, m.p.
139—139.5 C, Rf 0.49 (EtOAc—hexane, 1 : 2). IR, cm–1: 1628
(NC=O), 3280 (N—H). 1H NMR (600 MHz, DMSOꢀd6),
: 4.20, 5.21 (both d, 1 H each, NCH2, J =15.8 Hz); 5.79 (br.d,
1 H, H(2), J = 2.8 Hz); 6.14 (br.d, 1 H, HFur(3´), J = 3.4 Hz); 6.27
(dd, 1 H, HFur(4´), J = 2.1 Hz, J = 3.4 Hz); 6.64 (t, 1 H, H(6),
J = 7.6 Hz); 6.64 (dd, 1 H, H(8), J = 1.4 Hz, J = 7.6 Hz); 6.89 (dd,
1 H, HThien(4´), J = 3.4 Hz, J = 4.8 Hz); 7.00 (br.d, 1 H,
HThien(3´), J = 3.4 Hz); 7.18 (dt, 1 H, H(7), J = 1.4 Hz, J = 7.6 Hz);
7.32 (br.d, 1 H, NH, J = 2.8 Hz); 7.36 (dd, 1 H, HThien(5´),
J = 1.4 Hz, J = 4.8 Hz); 7.50 (br.d, 1 H, HFur(5´), J = 2.1 Hz);
7.60 (dd, 1 H, H(5) , J = 1.4 Hz, J = 7.6 Hz). 13C NMR
(150 MHz, CDCl3), : 42.4 (NCH2); 64.4 (C(2)); 108.4, 110.4
(CFur(3´), CFur(4´)); 114.9, 116.2, 119.6, 125.9, 126.8, 127.2,
128.7, 133.7 (Ar), 139.4 (CThien(2´)); 143.1 (CFur(5´)); 145.2,
152.1 (C(8a); CFur(2´)); 162.8 (C=O). MS, m/z (Irel (%)): 310
[M]+ (28), 171 (24), 170 (61), 143 (25), 115 (18), 112 (69),
97 (100), 92 (22). Found (%): C, 65.61; H, 4.43; N, 8.88; S, 10.45.
C17H14N2O2S. Calculated (%): C, 65.79; H, 4.55; N, 9.03;
S, 10.33.
3ꢀBenzylꢀ2ꢀ(2ꢀfurylꢀ5ꢀmethyl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀ
one (8h). The yield was 0.51 g (72%). Colorless fine needles,
m.p. 115 C, Rf 0.6 (EtOAc—hexane, 1 : 2). IR, cm–1: 1638
2ꢀ(2ꢀFuryl)ꢀ3ꢀ(2ꢀphenylethyl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀ
one (8e). The yield was 0.38 g (55%). Colorless spliced needles,
m.p. 147—148 C, Rf 0.51 (EtOAc—hexane, 1 : 2). IR, /cm–1
:
(NC=O), 3423 (N—H). H NMR (400 MHz, CDCl3), : 2.18
1

Synthesis of substituted quinazolinꢀ4ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 6, June, 2015
1351
(s, 3 H, Me); 3.91. 5.63 (both d, 1 H each, NCH2, J = 15.4 Hz);
4.61 (s, 1 H, NH); 5.54 (s, 1 H, H(2)); 5.80 (br.d, 1 H, HFur(4´),
J = 3.2 Hz); 6.05 (d, 1 H, HFur(3´), J = 3.2 Hz); 6.59 (d, 1 H,
H(8), J = 8.2 Hz); 6.85 (br.t, 1 H, H(6), J = 7.8 Hz); 7.24—7.36
(m, 6 H, Ar), 7.97 (dd, 1 H, H(5), J = 1.4 Hz, J = 7.8 Hz).
13C NMR (150 MHz, CDCl3), : 13.6 (Me); 47.4 (NCH2); 64.6
(C(2)); 106.3, 109.2, 114.8 (CFur(3´), CFur(4´), C(8)); 116.4
(C(4a)); 119.6, 127.6, 128.1, 128.7 (2C), 133.5 (Ar); 137.0 (C(1)
Ph); 145.3, 150.0, 152.7 (CFur(2´), CFur(5´), C(8a)); 163.2
(C=O). MS, m/z (Irel (%)): 318 [M]+ (8), 227 (18), 184 (10), 170
(43), 106 (17), 92 (19), 91 (100), 77 (12), 65 (22). Found (%):
C, 75.62; H, 5.83; N, 8.96. C20H18N2O2. Calculated (%):
C, 75.45; H, 5.70; N, 8.80.
114.8, 115.7, 119.1, 121.1, 123.6, 127.5, 127.9, 128.7, 128.8,
133.6, 136.9 (Ar, C(2)CH=CH, C(2)CH=CH); 142.7 (CFur(5´));
145.4, 151.1 (C(8a), CFur(2´)); 162.9 (C=O). MS, m/z (Irel (%)):
330 [M]+ (93), 240 (22), 239 (100), 197 (71), 170 (20), 160 (19),
120 (40), 106 (55), 92 (79), 91 (81), 77 (20), 76 (58), 65 (45), 51 (37),
43 (20). Found (%): C, 76.54; H, 5.32; N, 8.57. C21H18N2O2.
Calculated (%): C, 76.34; H, 5.49; N, 8.48.
3ꢀBenzylꢀ2ꢀ(2ꢀthienyl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀone (8l).
The yield was 0.37 g (53%). Colorless fine needles, m.p.
174—176 C, Rf 0.55 (EtOAc—hexane, 1 : 2). IR, cm–1: 1625
1
(NC=O), 3249 (N—H). H NMR (400 MHz, CDCl3), : 3.80,
5.65 (both d, 1 H each, NCH2, J = 15.6 Hz); 4.53 (s, 1 H, NH);
5.82 (d, 1 H, H(2), J = 2.3 Hz); 6.58 (d, 1 H, H(8), J = 8.2 Hz);
6.87—6.93 (m, 3 H, H(6), HThien(3´), HThien(4´)); 7.17 (dd, 1 H,
HThien(5´), J = 1.4 Hz, J = 5.0 Hz); 7.26—7.35 (m, 6 H, Ar);
8.01—8.02 (dd, 1 H, H(5), J = 0.9 Hz, J = 7.8 Hz). 13C NMR
(150 MHz, CDCl3), : 47.0 (NCH2); 66.7 (C(2)); 115.0 (C(8));
116.2 (C(4a)); 119.9 (CThien(3´)); 126.1, 126.3, 126.5, 127.7,
128.1, 128.8, 128.9, 133.8 (Ar, CThien(4´), CThien(5´)); 136.81
(C(1) Ph); 143.1 (CThien(2´)); 144.9 (C(8a)); 162.7 (C=O). MS,
m/z (Irel (%)): 320 [M]+ (14), 237 (18), 229 (82), 215 (18), 186
(36), 119 (16), 106 (38), 92 (20), 91 (100), 65 (18). Found (%):
C, 71.35; H, 4.88; N, 8.92; S, 10.29. C19H16N2OS. Calculatꢀ
ed (%): C, 71.22; H, 5.03; N, 8.74; S, 10.01.
3ꢀAllylꢀ2ꢀ(2ꢀfurylꢀ5ꢀmethyl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀ
one (8i). The yield was 0.28 g (47%). Colorless plates, m.p.
84.3—84.6 C, Rf 0.47 (EtOAc—hexane, 1 : 2). IR, cm–1: 1634
1
(NC=O), 3303 (N—H). H NMR (600 MHz, CDCl3), : 2.16
(s, 3 H, Me), 3.40 (dd, 1 H, J = 6.9 Hz, J = 15.8 Hz) and 4.89
(ddd, 1 H, CH2CH=CH2, J = 2.1 Hz, J = 4.1 Hz, J = 15.8 Hz);
4.65 (s, 1 H, NH); 5.17 (d, 1 H, J = 10.3 Hz) and 5.23 (d, 1 H,
CH2CH=CH2, J = 17.2 Hz); 5.60 (s, 1 H, H(2)); 5.76 (d, 1 H,
HFur(4´), J = 2.7 Hz); 5.78—5.83 (m, 1 H, CH2CH=CH2); 6.00
(d, 1 H, HFur(3´), J = 2.7 Hz); 6.57 (d, 1 H, H(8), J = 7.6 Hz);
6.80 (ddd, 1 H, H(6), J = 1.4 Hz, J = 7.6 Hz, J = 8.6 Hz); 7.21
(ddd, 1 H, H(7), J = 1.4 Hz, J = 7.6 Hz, J = 8.6 Hz); 7.88 (dd, 1 H,
H(5), J = 1.4 Hz, J = 7.6 Hz). 13C NMR (150 MHz, CDCl3),
: 13.6 (Me); 46.6 (CH2CH=CH2); 64.6 (C(2)); 106.3, 109.11
(CFur(3´), CFur(4´)); 116.4 (C(4a)); 114.8, 117.8, 119.3, 128.5,
132.9, 133.4 (Ar, CH2CH=CH2, CH2CH=CH2); 145.5, 150.3
(C(8a), CFur(2´)); 152.7 (CFur(5´)); 162.9 (C=O). MS, m/z
(Irel (%)): 268 [M]+ (45), 267 (23), 227 (56), 225 (34), 187 (56),
184 (28), 170 (100), 147 (84), 119 (44), 92 (32), 41 (36). Found (%):
C, 71.43; H, 5.89; N, 10.96. C16H16N2O2. Calculated (%): C, 71.62;
H, 6.01; N, 10.44.
2ꢀ(1ꢀBenzothienꢀ2ꢀyl)ꢀ3ꢀbenzylꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀ
one (8m). The yield was 0.46 (57%). Colorless fine needles, m.p.
173—173.3 C, Rf 0.53 (EtOAc—hexane, 1 : 2). IR, /cm–1: 1633
1
(NC=O), 3291 (N—H). H NMR (600 MHz, CDCl3), : 3.78,
5.69 (both d, 1 H each, NCH2, J = 15.8 Hz); 4.67 (br.s, 1 H,
NH); 5.83 (s, 1 H, H(2)); 6.56 (d, 1 H, H(8), J = 8.3 Hz); 6.87
(t, 1 H, H(6), J = 7.6 Hz); 7.08 (s, 1 H, HThien(3´)); 7.24—7.30
(m, 2 H) and 7.62—7.65 (m, 8 H, Ar), 8.00 (dd, 1 H, H(5),
J = 1.4 Hz, J = 7.6 Hz). 13C NMR (150 MHz, CDCl3), : 47.1
(NCH2); 67.2 (C(2)); 115.2 (C(8)); 116.2 (C(4a)); 119.9
(CThien(3´)); 122.6, 123.0, 123.9, 124.7, 125.2, 127.8, 128.2,
128.8, 128.9 133.9, 136.7, 138.6, 139.7, 143.6 (Ar); 144.8 (C(8a));
162.8 (C=O). MS, m/z (Irel (%)): 370 [M]+ (13), 279 (72),
265 (12), 237 (81), 147 (15), 134 (12), 119 (13), 106 (13), 92 (42),
91 (100), 76 (14), 65 (35), 43 (13). Found (%): C, 74.36; H, 4.79;
N, 7.77; S, 8.43. C23H18N2OS. Calculated (%): C, 74.57; H, 4.90;
N, 7.56; S, 8.66.
3ꢀBenzylꢀ2ꢀ(1Hꢀpyrrolꢀ2ꢀyl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀ
one (8n). The yield was 0.10 g (15%). Colorless needles, m.p.
126—127 C, Rf 0.48 (EtOAc—hexane, 1 : 2). IR, cm–1: 1609
(NC=O), 3254, 3437 (N—H). 1H NMR (600 MHz, CDCl3),
: 3.94, 5.22 (both d, 1 H each, NCH2, J = 15.1 Hz); 4.42 (br.s,
1 H, NH); 5.70 (s, 1 H, H(2)); 6.07 (q, 1 H, HPyrrol(4´),
J = 2.8 Hz); 6.11 (m, 1 H, HPyrrol(3´)); 6.57 (d, 1 H, H(8),
J = 8.2 Hz); 6.63 (m, 1 H, HPyrrol(5´)); 6.89 (t, 1 H, H(6),
J = 7.6 Hz); 7.17—7.29 (m, 6 H, Ar); 8.00 (dd, 1 H, H(5),
J = 1.4 Hz, J = 7.6 Hz); 8.21 (br.s, 1 H, NH). 13C NMR
(100 MHz, CDCl3), : 50.5 (NCH2); 77.3 (C(2)); 115.0, 115.6,
117.8, 124.6, 125.4, 127.5, 128.5, 128.9, 129.3, 130.2, 135.3,
137.3 (Ar); 147.5 (C(8a)); 160.1 (C=O). MS, m/z (Irel (%)):
303 [M]+ (41), 236 (15), 212 (77), 197 (20), 170 (17), 169 (93),
156 (15), 120 (46), 115 (25), 106 (41), 93 (18), 92 (62), 91 (100),
78 (21), 69 (21), 68 (82), 64 (15), 59 (14), 58 (41), 52 (21), 51 (29),
44 (18), 43 (74), 41(51). Found (%): C, 75.50; H, 5.33; N, 13.59.
C19H17N3O. Calculated (%): C, 75.23; H, 5.65; N, 13.85.
3ꢀBenzylꢀ2ꢀ(1ꢀtosylꢀ1Hꢀpyrrolꢀ2ꢀyl)ꢀ2,3ꢀdihydroquinazolinꢀ
4(1H)ꢀone (8o). The yield was 0.95 g (94%). Colorless needles,
3ꢀBenzylꢀ2ꢀ(2ꢀfurylꢀ5ꢀphenyl)ꢀ2,3ꢀdihydroquinazolinꢀ4(1H)ꢀ
one (8j). The yield was 0.33 g (40%). Brown prisms, m.p.
148—149 C, Rf 0.71 (EtOAc—hexane, 1 : 2). IR, cm–1: 1626
1
(NC=O), 3289 (N—H). H NMR (600 MHz, CDCl3), : 3.98,
5.70 (both d, 1 H each, NCH2, J = 15.1 Hz); 4.67 (br.d, 1 H,
NH, J = 2.8 Hz); 5.64 (d, 1 H, H(2), J = 2.8 Hz); 6.25 (d, 1 H,
HFur(4´), J = 3.4 Hz); 6.48 (d, 1 H, HFur(3´), J = 3.4 Hz); 6.61
(d, 1 H, H(8), J = 8.2 Hz); 6.89 (t, 1 H, H(6), J = 8.2 Hz);
7.23—7.37 (m, 9 H) and 7.49—7.50 (m, 2 H, Ar); 8.02 (dd, 1 H,
H(5), J = 1.4 Hz, J = 8.2 Hz). 13C NMR (100 MHz, CDCl3),
: 47.5 (NCH2); 64.6 (C(2)); 105.5, 110.2, 114.9, 116.4, 119.7,
123.8, 127.7, 127.8, 128.1, 128.7, 128.7, 128.8, 130.3, 133.6,
136.8, 145.3, 151.6, 154.3 (Ar); 163.2 (C=O). MS, m/z (Irel (%)):
380 [M]+ (41), 290 (20), 289 (100), 246 (16), 237 (19), 170 (52),
147 (35), 144 (56), 91 (52). Found (%): C, 79.00; H, 5.11; N, 7.48.
C25H20N2O2. Calculated (%): C, 78.93; H, 5.30; N, 7.36.
3ꢀBenzylꢀ2ꢀ[(E)ꢀ2ꢀ(2ꢀfuryl)vinyl]ꢀ2,3ꢀdihydroquinazolinꢀ
4(1H)ꢀone (8k). The yield was 58 mg (8%). A yellow powder,
m.p. 154—155 C, Rf 0.63 (EtOAc—hexane, 1 : 2). IR, cm–1
:
1645 (NC=O), 3376 (N—H). 1H NMR (600 MHz, CDCl3),
: 3.86, 5.59 (both d, 1 H each, NCH2, J = 15.4 Hz); 4.61 (br.s,
1 H, NH); 4.98 (br.d, 1 H, H(2), J = 5.5 Hz); 6.22—6.28 (m, 3 H,
HFur(3´), C(2)CH=CH, C(2)CH=CH); 6.34 (dd, 1 H, HFur(4´),
J = 2.1 Hz, J = 3.4 Hz); 6.60 (d, 1 H, H(8), J = 8.2 Hz); 6.83
(t, 1 H, H(6), J = 7.6 Hz); 7.24—7.34 (m, 7 H, Ar, HFur(5´));
7.96 (dd, 1 H, H(5), J = 1.4 Hz, J = 7.6 Hz). 13C NMR
(100 MHz, CDCl3), : 46.7 (NCH2); 69.8 (C(2)); 109.9, 111.5,

1352
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Zaytsev et al.
1
m.p. 196—197 C, Rf 0.51 (EtOAc—hexane, 1 : 2). IR, /cm–1
:
Isomer 9aA. H NMR (600 MHz, DMSOꢀd6), : 2.61, 3.17
(both d, 1 H each, H(10), H(10a), J = 9.3 Hz); 5.12 (d, 1 H,
H(9), J = 1.7 Hz); 6.05 (s, 1 H, H(6a)); 6.48 (dd, 1 H, H(8),
J = 1.7 Hz, J = 5.8 Hz); 6.55 (d, 1 H, H(7), J = 5.8 Hz); 7.23
(dt, 1 H, H(3), J = 1.0 Hz, J = 7.6 Hz); 7.54—7.57 (m, 1 H, H(2));
7.87 (dd, 1 H, H(4), J = 1.4 Hz, J =7.6 Hz); 8.12 (d, 1 H, H(1),
J = 1.0 Hz, J = 8.2 Hz); 8.94 (s, 1 H, NH).
Isomer 9aB. 1H NMR (600 MHz, DMSOꢀd6), : 2.63, 3.21
(both d, 1 H each, H(10), H(10a), J = 9.2 Hz); 5.13 (d, 1 H,
H(9), J = 1.4 Hz); 5.61 (s, 1 H, H(6a)); 6.53 (dd, 1 H, H(8),
J = 1.4 Hz, J = 5.7 Hz); 7.11 (d, 1 H, H(7), J = 5.7 Hz); 7.34 (dd,
1 H, H(3), J = 7.3 Hz, J = 8.0 Hz); 7.56 (d, 1 H, H(4),
J = 8.0 Hz); 7.62 (ddd, 1 H, H(2), J = 1.4 Hz, J = 7.3 Hz,
J = 8.0 Hz); 7.93 (dd, 1 H, H(1), J = 1.4 Hz, J = 8.0 Hz); 9.22
(s, 1 H, NH).
MS, m/z (Irel (%)): 312 [M]+ (4), 213 (67), 200 (27), 185 (11),
146 (19), 120 (100), 98 (39), 92 (72), 85 (23), 77 (16), 65 (66),
59 (35), 54 (47), 43 (26). Found (%): C, 61.42; H, 4.01; N, 9.09.
C16H12N2O5. Calculated (%): C, 61.54; H, 3.87; N, 8.97.
(6aRS,6bSR,9RS,10SR,10aRS)ꢀ9ꢀMethylꢀ5,11ꢀdioxoꢀ
6,6a,9,10,10a,11ꢀhexahydroꢀ5Hꢀ6b,9ꢀepoxyisoindolo[2,1ꢀa]ꢀ
quinazolineꢀ10ꢀcarboxylic acid (9bA) and (6aRS,6bRS,9SR,
10RS,10aSR)ꢀ9ꢀmethylꢀ5,11ꢀdioxoꢀ6,6a,9,10,10a,11ꢀhexaꢀ
hydroꢀ5Hꢀ6b,9ꢀepoxyisoindolo[2,1ꢀa]quinazolineꢀ10ꢀcarboxylic
acid (9bB). Physicochemical characteristics and elemental analꢀ
ysis data are given for the mixture of stereoisomers. A colorless
powder, m.p. 180—181 C (PriOH—DMF). IR, /cm–1: 1660,
1678 (NC=O), 1725(O—C=O), 3083, 3179 (N—H).
Isomer 9bA. 1H NMR (600 MHz, DMSOꢀd6), : 1.59 (s, 3 H,
Me); 2.69, 3.21 (both d, 1 H each, H(10), H(10a), J = 9.2 Hz);
6.01 (s, 1 H, H(6a)); 6.35, 6.63 (both d, 1 H each, H(7), H(8),
J = 5.5 Hz); 7.26 (t, 1 H, H(3), J = 7.8 Hz); 7.57—7.60 (m, 1 H,
H(2)); 7.91 (dd, 1 H, H(4), J = 1.4 Hz, J = 7.8 Hz); 8.25 (d, 1 H,
H(1), J = 8.2 Hz); 8.90 (s, 1 H, NH).
1150, 1167 (ns SO2), 1355 (nas SO2), 1643 (NC=O), 3383 (N—H).
1H NMR (600 MHz, DMSOꢀd6), : 2.35 (s, 3 H, Me); 3.47, 5.22
(both d, 1 H each, NCH2, J = 15.5 Hz); 5.93 (dd, 1 H, HPyrrol(3´),
J = 1.4 Hz, J = 3.4 Hz); 5.98 (d, 1 H, H(2), J = 4.1 Hz); 6.15
(t, 1 H, HPyrrol(4´), J = 3.4 Hz); 6.76 (d, 1 H, NH, J = 4.1 Hz);
6.64—6.68 (m, 2 H), 7.02—7.42 (m, 8 H) and 7.63—7.66 (m, 3 H,
Ar); 7.38 (dd, 1 H, HPyrrol(5´), J = 1.4 Hz, J = 3.4 Hz). 13C NMR
(100 MHz, DMSOꢀd6), : 21.1 (Me); 47.0 (NCH2); 63.1 (C(2));
112.2, 114.3, 115.1, 115.8, 118.1, 124.8, 124.9, 126.5, 127.2,
127.3, 128.6, 130.3, 132.8, 133.2, 135.3, 137.0, 144.5, 145.7 (Ar);
162.5 (C=O). MS, m/z (Irel (%)): 457 [M]+ (51), 366 (29), 259
(15), 237 (27), 236 (57), 221 (60), 212 (20), 198 (35), 197 (43),
185 (74), 170 (16), 169 (65), 157 (20), 156 (27), 155 (45), 130 (22),
119 (47), 106 (33), 92 (100), 91 (79), 78 (18), 76 (23), 67 (15),
65 (25), 52 (18), 43 (28), 41 (15). Found (%): C, 68.41; H, 4.78;
N, 9.40; S, 6.81. C26H23N3O3S. Calculated (%): C, 68.25;
H, 5.07; N, 9.18; S, 7.01.
Synthesis of 3ꢀbenzylꢀ2ꢀ(2ꢀfuryl)ꢀ2,3ꢀdihydroquinazolinꢀ
4(1H)ꢀone 8b using oneꢀpot method. Benzylamine (0.7 mL,
6.4 mmol) was added to a solution of isatoic anhydride (1.0 g,
6.1 mmol) in MeCN (50 mL), and the mixture was stirred for 4 h
at 50 C (TLC monitoring), cooled to room temperature, folꢀ
lowed by a sequential addition of TsOH (0.6 g, 3 mmol) and
furfural (0.5 mL, 6.1 mmol). The reaction mixture was stirred for
24 h and poured into water (50 mL), after the addition of an
aqueous solution of NaHCO3 the mixture was extracted with
CHCl3 (3×20 mL). The extract was dried with anhydrous MgSO4.
The residue after removal of CHCl3 was purified by recrystalliꢀ
zation from a mixture of EtOAc—hexane to obtain 8b (1.23 g,
66%) as colorless spliced needles with m.p. 175—176 C. A mixed
probe with the authentic sample obtained by the preceding methꢀ
od showed no melting point depression.
6b,9ꢀEpoxyisoindolo[2,1ꢀa]quinazolineꢀ10ꢀcarboxylic acids
(9a,b) (general procedure). A. A mixture of quinazoline 2a,b
(4.4 mmol) and maleic anhydride (0.43 g, 4.6 mmol) in CHCl3
(20 mL) was stirred for 4 h (TLC monitoring). The crystals
formed were filtered, washed with diethyl ether (2×20 mL), and
dried in air to obtain a mixture of Aꢀ and Bꢀisomers of the
Diels—Alder adducts 9a,b as colorless powders. The yields and
the ratios of Aꢀ and Bꢀstereoisomers: 0.88 g (60%) 9a, 65 : 35 and
0.73 g (51%) 9b, 30 : 70.
B. Furfural (4.14 mL, 0.05 mol) and anhydrous MgSO4 (12.0 g,
0.1 mol) were added to a solution of 2ꢀaminobenzamide 1 (6.81 g,
0.05 mol) in CHCl3 (100 mL), the mixture was stirred for 2 h
(TLC monitoring) and filtered. The residue was washed with
CHCl3 (2×20 mL), the combined mother liquor was half conꢀ
centrated. Maleic anhydride (5.39 g, 0.055 mol) was added to
the solution obtained, which was stirred for 30 min. The crystals
formed were filtered and washed with ether (2×20 mL) to obtain
a mixture of Aꢀ and Bꢀstereoisomers of 9a (15.3 g, 94%) (65 : 35)
as a colorless powder.
Isomer 9bB. 1H NMR (600 MHz, DMSOꢀd6), : 1.57 (s, 3 H,
Me); 2.70, 3.26 (both d, 1 H each, H(10), H(10a), J = 8.7 Hz);
5.63 (s, 1 H, H(6a)); 6.40, 7.17 (both d, 1 H each, H(7), H(8),
J = 5.5 Hz); 7.38 (t, 1 H, H(3), J = 7.8 Hz); 7.47 (t, 1 H, H(2),
J = 7.8 Hz); 7.97 (dd, 1 H, H(4), J = 1.4 Hz, J = 7.8 Hz); 8.11
(d, 1 H, H(1), J = 7.8 Hz); 9.21 (s, 1 H, NH).
MS, m/z (Irel (%)): 326 [M]+ (1), 226 (100), 211 (65), 197
(25), 183 (11), 170 (7), 120 (26), 101 (43), 59 (52). Found (%):
C, 62.50; H, 4.17; N, 8.76. C17H14N2O5. Calculated (%): C, 62.57;
H, 4.32; N, 8.59.
This work was financially supported by the Russian
Foundation for Basic Research (Project Nos 13ꢀ03ꢀ00105
and 13ꢀ03ꢀ90400).
References
(6aRS,6bSR,9RS,10SR,10aRS)ꢀ5,11ꢀDioxoꢀ6,6a,9,10,
10a,11ꢀhexahydroꢀ5Hꢀ6b,9ꢀepoxyisoindolo[2,1ꢀa]quinazolineꢀ
10ꢀcarboxylic acid (9aA) and (6aRS,6bRS,9SR,10RS,10aSR)ꢀ
5,11ꢀdioxoꢀ6,6a,9,10,10a,11ꢀhexahydroꢀ5Hꢀ6b,9ꢀepoxyisoindoloꢀ
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characteristics and elemental analysis data are given for the mixꢀ
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(PriOH—DMF). IR, /cm–1: 1675 (NC=O), 1723 (O—C=O),
3183 (N—H).
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Received January 15, 2015;
in revised form March 13, 2015