Fluorine-containing quinazolines annulated at the pyrimidine ring

Article abstract of DOI:10.1007/s11172-009-0171-7

containing quinazolines annulated at the sides [a] and [c] were synthesized by the reaction of 2-and 4-hydrazino-substituted quinazolines with aldehydes and subsequent oxidative cyclization. Annulation at the side [b] was performed by alkylation of 2-alky

Full text of DOI:10.1007/s11172-009-0171-7

Russian Chemical Bulletin, International Edition, Vol. 58, No. 6, pp. 1303—1308, June, 2009
1303
Fluorineꢀcontaining quinazolines
annulated at the pyrimidine ring*
E. V. Nosova,a A. A. Laeva,a T. V. Trashakhova,a G. N. Lipunova,b
P. A. Slepukhin,b and V. N. Charushinb
aUral State Technical University — UPI,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Eꢀmail: emily74@rambler.ru
bI. Ya. Postovskii Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Eꢀmail: charushin@ios.uran.ru
Fluorineꢀcontaining quinazolines annulated at the sides [a] and [c] were synthesized by the
reaction of 2ꢀ and 4ꢀhydrazinoꢀsubstituted quinazolines with aldehydes and subsequent oxidaꢀ
tive cyclization. Annulation at the side [b] was performed by alkylation of 2ꢀalkylthioꢀ4(3H)ꢀ
quinazolinones with bromoethanol and ipsoꢀsubstitution of the alkylthio group.
Key words: fluorineꢀcontaining quinazolinꢀ4ꢀones, alkylation, hydrazones, cyclocondenꢀ
sation, oxidative cyclization, triazoloquinazolines.
Scheme 1
Annulated fluorineꢀcontaining quinazolinꢀ4ꢀone
derivatives are prospective objects for the medicinal chemꢀ
istry. For instance, tetrafluoroꢀsubstituted pyridoꢀ and
pyrimidino[b]ꢀannulated quinazolinones display antiꢀ
tumor activity,1 whereas in a number of pyrido[a]ꢀannulated
quinazolinones, there were found compounds possessing
tuberculostatic activity.2
Earlier,6 we have shown that 2ꢀalkylthioꢀ6,7,8ꢀtriꢀ
fluoroquinazolinꢀ4(3H)ꢀones 1a,b, obtained according to
Scheme 2, have several reaction centers in one molecule,
therefore, they are convenient objects for the modificaꢀ
tion based on nucleophilic substitution reactions.
In continuation of this research, we studied a possiꢀ
bility to modify the fluorineꢀcontaining 2ꢀalkylthioꢀ
quinazolinones 1a,b by annulation of the rings at different
sides of the pyrimidine ring.
X = CH, N
We have suggested3—5 efficient methods for the assemꢀ
bling fused systems, in which quinazoline framework has
the [a] or [b] connection with pyridine, imidazole,
triazole, pyrazole, or thiazole rings. The methods sugꢀ
gested are based on the cyclocondensation of orthoꢀfluoroꢀ
benzoyl chlorides with aminoazoles and aminoazines as
N,N´ꢀdinucleophiles (Scheme 1).
It should be noted that this approach offers limited
choice in additional ring and does not allow one to
perform annulation at the side [c] of the quinazoline
framework.
We suggested that the reaction of 1a with 2ꢀbromoꢀ
ethanol will lead to oxazino[i,j]ꢀannulated quinazoline 2
(the azaꢀanalog of ofloxacine, the highly active antibacteꢀ
rial agent7) resulting from the Nꢀalkylation reaction of 1a
at position 1 and subsequent intramolecular substitution
of the fluorine atom (Scheme 3). However, the presence
* Dedicated to Academician O. N. Chupakhin on the occasion
of his 75th birthday.
1
in the H NMR spectrum of the reaction product of the
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1266—1271, June, 2009.
1066ꢀ5285/09/5806ꢀ1303 © 2009 Springer Science+Business Media, Inc.

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Nosova et al.
Scheme 2
Scheme 3
i.
, NEt3; ii. DMF, t. Alk = Et (1a), Me (1b)
signal for the proton of the trifluorobenzene fragment in
the form of a double doublet of doublets with the constants
3J = 9.9, 4J = 7.5, 5J = 2.0 Hz, as well as the absence of the
signals for the protons of the ethyl group, allowed us to
suggest that the Nꢀalkyl intermediate A undergoes
nucleophilic substitution of the —SEt group, rather than
the fluorine atom, and is converted to compound 3.
The presence of an intensive peak of the molecular
ion m/z 242 in the mass spectrum of the compound obꢀ
tained confirms this suggestion. The spectral data menꢀ
tioned, however, contradict with neither the structure of
oxazolo[a]ꢀannulated quinazolinone 3 nor the alternative
structure of oxazolo[b]ꢀannulated quinazolinone 4, formed
resulting from the initial attack of the alkylating agent on
position 3 of compound 1a. The alkylation reaction at
position 3 of 6ꢀfluoroquinazolinꢀ4ꢀone under phaseꢀtransꢀ
fer catalysis conditions is described in Ref. 8.
tural analysis, which allowed us to assign the structure
of 7,8,9ꢀtrifluoroꢀ2,3ꢀdihydrooxazolo[2,3ꢀb]quinazolinꢀ
5ꢀone (4) to it (Fig. 1). According to the Xꢀray analysis
data, the oxazoline fragment is not planar, the deviation
of atoms C(1) and C(2) from the meanꢀsquare plane of
the quinazoline ring reaches 0.170 Å. A large scatter is
observed for the bond distances in the pyrimidine ring
(from 1.272(2) Å for the bond N(2)—C(3) to 1.459(2) Å
for the bond C(9)—C(10)), which indicates strong disturbꢀ
ance brought into the aromatic system by the annulated
dihydrooxazole and the keto group oxygen. Other bond
distances and bond angles are close to standard values.
Annulation of the triazole ring at the [a] side of the
fluorineꢀcontaining quinazolinꢀ4ꢀone 1a is of interest as
a convenient method for obtaining fluorinated analogs of
antihistamine and antiasthma agents,9,10 as well as comꢀ
pounds exhibiting antiꢀHIV, antibacterial, and antifungal
activity.11 To implement such a modification, we used
The reaction product of quinazolinone 1a with
2ꢀbromoethanol we studied by Xꢀray diffraction strucꢀ
O(2)
F(3)
C(9)
C(7)
C(6)
N(1)
C(3)
C(8)
C(5)
C(10)
C(1)
C(2)
C(4)
F(2)
O(1)
N(2)
F(1)
Fig. 1. Molecular structure of 7,8,9ꢀtrifluoroꢀ2,3(dihydro)ꢀ
oxazolo[2,3ꢀb]quinazolinꢀ5ꢀone (4).

Fluorinated quinazolines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
1305
2ꢀhydrazinoquinazolinꢀ4ꢀone 6, the synthesis of which
through the compound 5 has been described by us earꢀ
lier.6 Hydrazones 7a,b were obtained upon reflux of 6
with the corresponding aldehyde in ethanol (Scheme 4),
the oxidative cyclization of 7a,b into triazoloquinazolinꢀ
ones 8 was performed upon heating in alcoholic solution
of iron(III) chloride under conditions used for the transꢀ
formation of aldose hydrazones and (4ꢀoxoquinazolinꢀ
2ꢀyl)hydrazine into the corresponding angular triazoloꢀ
quinazolinones.12
analyzed the 19F NMR spectra of triazoloquinazolinones
8a,b. The signal for F(9) of quinazolinones in these comꢀ
pounds has more complicated multiplicity (dddd) than
the signal for F(7) (ddd). This can be explained by the
presence of interaction of F(9) not only with F(7), H(6),
and the proton of the pyrrolidine fragment, but also with
the proton of the phenyl or furyl substituent at position 1,
which is evidence in favor of the structure 8. It should be
noted that the spinꢀspins constant values of the interactꢀ
ion F(9)—H(5´) (1.9 Hz) agrees with the data obtained
by us earlier for other fluorineꢀcontaining polycyclic
benzazines.14
Scheme 4
Another modification of pyrimidine fragment in
fluorineꢀcontaining quinazolines consists in annulation
of the triazole ring at the side [c] to create fluorineꢀconꢀ
taining analogs of compounds exhibiting antiinflammaꢀ
tory activity,15 such a modification is possible by introꢀ
duction of a hydrazino group at position 4 of quinazoline
(Scheme 5).
To accomplish this, 4ꢀchloroquinazoline 10, obtained
according to the procedure described earlier,6 was kept
with hydrazine hydrate in ethanol at room temperature.
The mild reaction conditions allowed us to avoid nucleoꢀ
philic substitution at positions 2 and 7 and perform the
reaction at the center the most active to the SNꢀreaction,
viz., position 4, to yield 4ꢀhydrazinoquinazoline 11 (see
Scheme 5).
7, 8: R = Ph (a), furanꢀ2ꢀyl (b)
Fluorineꢀcontaining [1,2,4]triazolo[c]ꢀquinazolines
13a,b were obtained by the reaction of hydrazine 11 with
benzaldehyde or pyridineꢀ2ꢀcarbaldehyde and subsequent
cyclization of hydrazones 12a,b in acetic acid in the presꢀ
ence of bromine under conditions used for the formation
of nonfluorinated triazoloquinazolines15 (Scheme 5). The
triazole ring closure is indicated by the disappearance of
the signal for the NH in the region 4.3—5.7 ppm and the
singlet for the proton CH=N in the region 8.4—8.6 ppm.
In the tricyclic compounds 13a,b, the signal for the proton
of the trifluorobenzene fragment is insignificantly shifted
upfield as compared to the corresponding signal in hydrꢀ
azones 12a,b. The mass spectrum of tricyclic derivative 13b
is characterized by the 100% peak of molecular ion.
In conclusion, the use of fluorineꢀcontaining 2ꢀalkylꢀ
thioꢀsubstituted quinazolinꢀ4(3H)ꢀones in the reactions
1
In the H NMR spectra of triazoloquinazolinones 8,
there are remained the signals for the phenyl (furyl) resiꢀ
dues, whereas the disappearance of one NH signal and
the singlet for the proton of the CH=N group in the
region 7.9—8.1 ppm confirms the occurrence of cyclizaꢀ
tion. The broad singlet of the NH in the cyclization prodꢀ
ucts of hydrazones appears in the region 13.2—13.5 ppm,
whereas the signal for the proton of the difluorobenzene
fragment is insignificantly downfield shifted (by 0.14 ppm
as compared to analogous signal for hydrazones 7a,b).
According to the literature data,13 the intramolecular
cyclization of hydrazones, obtained from 2ꢀhydrazinoꢀ
quinazolinones and aromatic aldehydes, leads to triazoloꢀ
quinazolinones of angular structure. To exclude the strucꢀ
ture of alternative products of linear structure 9, we have

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Nosova et al.
Scheme 5
a CCDꢀdetector (OxfordꢀDiffraction) according to the standard
procedure (MoKαꢀirradiation 0.71073 Å, a graphite monochroꢀ
mator, 295(2) K, ωꢀscanning, the step of scanning was 1°).
A monocrystal of compound 4 obtained by crystallization
from toluene was used for the analysis. A colorless plate
(0.47×0.35×0.07 mm), the crystal system is monoclinic, the space
group is C2/c, parameters of the unit cell are a = 21.821(6) Å,
b = 5.0446(15) Å, c = 19.883(7) Å, α = 90.000°, β = 120.023(8)°,
γ = 90.000°, V = 1895.0(10) Å3, Z = 8, dcalc = 1.698. The
structure was solved and refined by a direct method using
the SHELX97 program package16 by the least squares method
in anisotropic (isotropic for the H atoms) fullꢀmatrix approxiꢀ
mation. One part of hydrogen atoms was included into the
refinement by direct method, another part was placed into
geometrically calculated positions and included into the refineꢀ
ment by the riding model with dependent thermal parameters.
Correction on the absorption was not made due to its low value
(μ = 0.159 mm–1). It were collected 6525 reflections, from which
1845 were independent (Rint = 0.0421), 829 with I > 2σ(I). The
number of refining parameters was 158. The completeness of
scanning was 95.3% on the angles θ < 26.37. The divergence
factors were R1= 0.0333, wR2= 0.0377 (on the reflections with
I > 2σ(I)), R1 = 0.1140, wR2 = 0.0408 (on all the reflections),
The confidence factor was S = 1.001. The maximum and
minimum peaks of residual electron density were 0.104
and –0.128 e Å–3
.
The main interatomic distances and bond angles are given
in Tables 1 and 2, respectively.
Table 1. Main interatomic distances (d) in the molecule of 4
12, 13: R = pyridinꢀ2ꢀyl (a), P(b)
Bond
d/Å
Bond
d/Å
N(1)—C(3)
N(1)—C(10) 1.3831(18)
1.3669(18)
C(9)—C(8)
C(5)—C(6)
C(7)—C(8)
C(7)—F(3)
C(7)—C(6)
C(6)—F(2)
C(8)—H(8)
C(1)—C(2)
C(1)—H(1A) 0.9700
C(1)—H(1B) 0.9700
C(2)—H(2A) 0.9700
C(2)—H(2B) 0.9700
1.403(2)
1.350(2)
1.350(2)
1.364(2)
1.371(2)
1.350(2)
0.925(14)
1.5147(18)
with bifunctional reagents opens prospects for the prepaꢀ
ration of earlier unavailable fluorineꢀcontaining fused
systems.
Results of the Xꢀray diffraction study were deposited
with the Cambridge Structural Database.*
N(1)—C(1)
C(4)—N(2)
C(4)—C(5)
C(4)—C(9)
N(2)—C(3)
F(1)—C(5)
O(1)—C(3)
O(1)—C(2)
1.4577(17)
1.3890(18)
1.397(2)
1.396(2)
1.272(2)
1.3507(19)
1.3396(18)
1.4468(17)
Experimental
1H NMR spectra were recorded on a Bruker WMꢀ250
and Bruker DRXꢀ400 spectrometers (250.14 and 400.13 MHz),
19F NMR spectra were recorded on a Bruker DRXꢀ500 spectroꢀ
meter (376.45 MHz). Tetramethylsilane (1H NMR) or hexaꢀ
fluorobenzene (19F NMR) were used as internal standards,
DMSOꢀd6, as a solvent. Mass spectra were obtained on a Varian
MAT 311A instrument (experimental conditions: accelerating
potential, 3 kV, cathode emission current, 300 μA, energy of
ionizing electrons, 70 eV, direct injection of sample into the
source), as well as on a Shimadzu LCMSꢀ2010 liquid GCꢀMS
spectrometer (registration of positive and negative ions; modes
for the registration of ions: scanning of given interval of masses,
SIM, profile scanning; APCI (atmospheric pressure chemical
ionization).
C(10)—O(2) 1.2164(17)
C(10)—C(9) 1.459(2)
Table 2. Main bond angles (ω) in the molecule of 4
Angle ω/deg Angle
C(3)—N(1)—C(10) 122.95(15) C(8)—C(7)—C(6) 121.7(2)
C(3)—N(1)—C(1) 111.84(14) C(6)—C(5)—F(1) 118.8(2)
C(10)—N(1)—C(1) 124.91(15) C(6)—C(5)—C(4) 122.0(2)
ω/deg
N(2)—C(4)—C(5) 118.47(19) F(1)—C(5)—C(4)
N(2)—C(4)—C(9) 124.57(16) C(8)—C(7)—F(3)
119.1(2)
120.5(2)
C(5)—C(4)—C(9) 116.96(18) N(1)—C(1)—C(2) 100.89(12)
C(3)—N(2)—C(4) 113.19(16) O(1)—C(2)—C(1) 106.27(12)
C(3)—O(1)—C(2) 109.48(13) N(2)—C(3)—O(1) 122.27(18)
O(2)—C(10)—N(1) 120.78(17) N(2)—C(3)—N(1) 127.79(18)
O(2)—C(10)—C(9) 127.18(17) O(1)—C(3)—N(1) 109.94(17)
N(1)—C(10)—C(9) 112.03(16) C(8)—C(9)—C(10) 119.8(2)
C(8)—C(9)—C(4) 120.8(2) C(4)—C(9)—C(10)119.38(16)
The Xꢀray diffraction structural analysis was performed on a
Xcalibur 3 automatic fourꢀcircle diffractometer equipped with
* These materials are freely available on request at
www.ccdc.cam.ac.uk/ data_request/cif.

Fluorinated quinazolines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 6, June, 2009
1307
7,8,9ꢀTrifluoroꢀ2,3ꢀdihydrooxazolo[2,3ꢀb]quinazolinꢀ5ꢀone
(4). 2ꢀBromoethanol (0.3 mL, 3.8 mmol) and 30% aqueous
NaOH (0.62 mL) were added to a solution of quinazolinone 1a
(0.5 g, 1.9 mmol) in ethanol (5 mL). The reaction mixture was
refluxed for 3 h and concentrated, the residue was washed with
water and recrystallized from ethanol to obtain compound 4.
The yield was 0.34 g (74%), m.p. 310—312 °C. 1H NMR
(DMSOꢀd6), δ: 4.31 (m, 3 H, CH2); 4.81 (m, 2 H, CH2);
7.73 (ddd, 1 H, H(5), 3J = 9.9 Hz, 4J = 7.5 Hz, 5J = 2.0 Hz).
MS (EI), m/z (Irel (%)): 242 (65) [M]+, 200 [M – C2H2O]+
(100). Found (%): C, 49.61; H, 2.11; N, 11.53. C10H5F3N2O2.
Calculated (%): C, 49.60; H, 2.08; N, 11.57.
2ꢀ(N´ꢀBenzylidenehydrazino)ꢀ6,8ꢀdifluoroꢀ7ꢀpyrrolidinoꢀ
3Hꢀquinazolinꢀ4ꢀone (7a). Benzaldehyde (0.3 mL, 3.2 mmol)
was added to a suspension of 2ꢀhydrazinoquinazolinꢀ4ꢀone 6
(0.6 g, 2.14 mmol) in ethanol (15 mL). The reaction mixture
was refluxed for 1.5 h. After cooling, a precipitate of compound
7a was filtered off and recrystallized from dimethylsulfoxide.
The yield was 0.56 g (71%), m.p. 260—262 °C. 1H NMR
(DMSOꢀd6), δ: 1.90 (m, 4 H, (CH2)2); 3.60 (m, 4 H, N(CH2)2);
7.1—7.48 (m, 4 H, Ph); 7.75 (m, 2 H, H(5), Ph); 8.21 (s, 1 H,
CH=N); 10.9 (br.s, 1 H, NH); 11.6 (br.s, 1 H, NH). Found (%):
C, 61.69; H, 4.55; N, 19.02. C19H17F2N5O. Calculated (%):
C, 61.73; H, 4.60; N, 18.95.
6,8ꢀDifluoroꢀ2ꢀ(N´ꢀfuranꢀ2ꢀylmethylidenehydrazino)ꢀ7ꢀpyrꢀ
rolidinoꢀ3Hꢀquinazolinꢀ4ꢀone (7b) was obtained similarly
to 7a from quinazolinone 6 and furfurol. The yield was 88%,
m.p. 276—278 °C. 1H NMR (DMSOꢀd6), δ: 1.93 (m, 4 H,
(CH2)2); 3.66 (m, 4 H, N(CH2)2); 6.53 (m, 1 H, furyl); 6.98 (m,
1 H, furyl); 7.32 (dd, 1 H, H(5), 3J = 14.2 Hz, 5J = 2.0 Hz); 7.65
(m, 1 H, furyl); 7.93 (s, 1 H, CH=N); 10.3 (br.s, 1 H, NH); 11.8
(br.s, 1 H, NH). Found (%): C, 56.76; H, 4.16; N, 19.56.
C17H15F2N5O2. Calculated (%): C, 56.82; H, 4.21; N, 19.49.
7,9ꢀDifluoroꢀ1ꢀphenylꢀ8ꢀpyrrolidinoꢀ4Hꢀ[1,2,4]triazoloꢀ
[4,3ꢀa]quinazolinꢀ5ꢀone (8a). A solution of FeCl3 in ethanol
(2 M, 1.2 mL) was added to a boiling suspension of hydrazone 7a
(0.55 g, 1.5 mmol) in ethanol (20 mL). The reaction mixture
was refluxed for 1 h, then, kept at room temperature for 1 day.
A colorless precipitate of compound 8a was filtered off, washed
with water, and recrystallized from DMSO. The yield was 0.4 g
(72%), m.p. 320—322 °C. 1H NMR (DMSOꢀd6), δ: 1.88 (m, 4 H,
(CH2)2); 3.61 (m, 4 H, N(CH2)2); 7.3—7.5 (m, 5 H, Ph); 7.89
(m, 1 H, H(6)); 13.2 (br.s, 1 H, NH). 19F NMR (DMSOꢀd6), δ:
ice, a precipitate was filtered off, dissolved in ethanol (5 mL)
followed by addition of hydrazine hydrate (0.15 mL, 3.0 mmol).
The reaction mixture was stirred for 3 h at room temperature. A
precipitate was filtered off and recrystallized from ethanol. The
yield was 0.61 g (78%), m.p. 191—193 °C. 1H NMR (DMSOꢀd6),
δ: 2.50 (s, 3 H, CH3); 6.82 (br.s, 3 H, —NH—NH2); 8.11 (m,
1 H, H(5)). Found (%): C, 41.45; H, 2.80; N, 21.41. C9H7F3N4S.
Calculated (%): C, 41.54; H, 2.71; N, 21.53.
Nꢀ(6,7,8ꢀTrifluoroꢀ2ꢀmethylthioquinazolinꢀ4ꢀyl)ꢀN´ꢀ(pyridinꢀ
2ꢀylmethylidene)hydrazine (12a). Pyridineꢀ2ꢀcarbaldehyde
(0.25 mL, 2.3 mmol) was added to a solution of hydrazine 11
(0.4 g, 1.5 mmol) in anhydrous ethanol (9 mL). The reaction
mixture was stirred for 1 h at 50—60 °C. After cooling, a precipiꢀ
tate was filtered off and recrystallized from ethanol. The yield
1
was 0.42 g (80%), m.p. 191—193 °C. H NMR (DMSOꢀd6), δ:
2.46 (s, 3 H, CH3); 5.67 (s, 1 H, NH); 7.43 (m, 1 H, pyridine);
7.95 (m, 1 H, pyridine); 8.11 (m, 1 H, H(5)); 8.45 (s, 1 H,
N=CH); 8.63 (m, 2 H, pyridine). Found (%): C, 51.55; H, 2.83;
N, 20.01. C15H10F3N5S. Calculated (%): C, 51.57; H, 2.89;
N, 20.05.
NꢀBenzylideneꢀN´ꢀ(6,7,8ꢀtrifluoroꢀ2ꢀmethylthioquinazolinꢀ
4ꢀyl)hydrazine (12b) was obtained similarly to 12a from hydrazine
11 and benzaldehyde. The yield was 83%, m.p. 180—182 °C.
1H NMR (DMSOꢀd6), δ: 2.50 (s, 3 H, CH3); 4.25 (s, 1 H, NH);
7.45 (m, 3 H, Ph); 7.77 (m, 2 H, Ph); 8.32 (m, 1 H, H(5)); 8.61
(s, 1 H, N=CH). Found (%): C, 55.17; H, 3.16; N, 16.01.
C16H11F3N4S. Calculated (%): C, 55.17; H, 3.18; N, 16.08.
7,8,9ꢀTrifluoroꢀ5ꢀmethylthioꢀ3ꢀ(pyridinꢀ2ꢀyl)ꢀ1,2,4ꢀtriazoloꢀ
[4,3ꢀc]quinazoline (13a). A solution of bromine (0.12 mL) in
glacial acetic acid (0.6 mL) was added to a suspension of
compound 12a (0.8 g, 2.3 mmol) and anhydrous sodium acetate
(1.8 g) in glacial acetic acid (8 mL). The reaction mixture was
stirred for 3 h at room temperature, followed by addition of 20%
aq. NaOH (20 mL). A precipitate was filtered off and recrystalꢀ
lized from DMSO. The yield was 0.59 g (74%), m.p. 290—292 °C.
1H NMR (DMSOꢀd6), δ: 2.52 (s, 3 H, CH3); 7.46 (m, 1 H,
pyridine); 7.82 (m, 1 H, pyridine); 7.94 (m, 1 H, H(5)); 8.30 (m,
1 H, pyridine); 8.71 (m, 1 H, pyridine). Found (%): C, 51.80;
H, 2.33; N, 20.11. C15H8F3N5S. Calculated (%): C, 51.87;
H, 2.32; N, 20.16.
7,8,9ꢀTrifluoroꢀ5ꢀmethylthioꢀ3ꢀphenylꢀ1,2,4ꢀtriazoloꢀ
[4,3ꢀc]quinazoline (13b) was obtained similarly to 13a. The yield
was 76%, m.p. 191—193 °C. 1H NMR (DMSOꢀd6), δ: 2.55 (s,
3 H, CH3); 7.55 (m, 3 H, Ph); 7.65 (m, 2 H, Ph); 8.23 (m,
1 H, H(5)). MS (CI), m/z (Irel (%)): 347 [M + H]+ (66), 388
[M + H + CH3CN]+ (100). Found (%): C, 55.51; H, 2.63;
N, 10.11. C16H9F3N4S. Calculated (%): C, 55.49; H, 2.62;
N, 10.18.
3
4
127.60 (ddd, 1 F, F(7), JH(6),F = 10.0 Hz, JF,F = 7.8 Hz,
5JH(2´),F = 1.9 Hz); 143.67 (dddd, 1 F, F(9), JF,F = 7.8 Hz,
4
7JH(2 ),F= 3.8 Hz, 5JH(6),F = 2.5 Hz, 5JH(5´),F = 1.9 Hz). MS (CI),
″
m/z (Irel (%)): 368 [M + H]+ (81), 409 [M + H + CH3CN]+
(100). Found (%): C, 62.12; H, 4.13; N, 18.99. C19H15F2N5O.
Calculated (%): C, 62.06; H, 4.08; N, 19.05.
This work was financially supported by the American
Civilian Research and Development Foundation (Proꢀ
gram BRHE, Grant CRDF BP2M05, Advanced Organic
Materials for Medical and Biological Application) and
the Russian Federation President Council for Grants (Proꢀ
gram for the State Support of Leading Scientific Schools,
Grant NShꢀ9178.2006.3).
7,9ꢀDifluoroꢀ1ꢀ(2ꢀfuryl)ꢀ8ꢀpyrrolidinoꢀ4Hꢀ[1,2,4]triazoloꢀ
[4,3ꢀa]quinazolinꢀ5ꢀone (8b) was obtained similarly to 8a. The
yield was 75%, m.p. 287—289 °C. 1H NMR (DMSOꢀd6), δ: 1.90
(m, 4 H, (CH2)2); 3.68 (m, 4 H, N(CH2)2); 6.70 (m, 1 H, furyl);
7.43 (m, 1 H, furyl); 7.49 (m, 1 H, H(6)); 7.92 (m, 1 H, furyl);
13.5 (br.s, 1 H, NH). 19F NMR (DMSOꢀd6), δ : 127.44 (dd,
1 F, F(7), 3JH(6),F = 8.9 Hz, 4JF,F = 6.1 Hz); 143.F92 (dddd, 1 F,
4
7
5
F(9), JF,F = 6.1 Hz, JH(2 ),F = 3.2 Hz, JH(6),F = 2.1 Hz,
″
5JH(5´),F = 1.4 Hz). Found (%): C, 57.09; H, 3.60; N, 19.65.
C17H13F2N5O2. Calculated (%): C, 57.14; H, 3.67; N, 19.60.
4ꢀHydrazinoꢀ6,7,8ꢀtrifluoroꢀ2ꢀmethylthioquinazoline (11).
A solution of quinazolinone 1a (0.7 g, 3.0 mmol) was refluxed
for 2 h in POCl3 (4 mL). The reaction mixture was poured on
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Received March 10, 2009