Modification of biologically active amides and amines with fluorine-containing heterocycles: 2*. N-(2-thienyl)imines on the base of methyl trifluoropyruvate in cyclocondensation with 1,3-N, N-binucleophiles

Article abstract of DOI:10.1007/s11172-010-0062-y

An approach to the modification of the biologically active compounds, substituted 2-aminothiophenes, with fluorine-containing five-membered heterocycles is proposed. The reaction of 2-aminothiophenes with methyl trifluoropyruvate yields the corresponding N-(2-thienyl)imines, their subsequent cyclocondensation with 1,3-N,N-binucleophiles (2-aminothiazoline and benzamidines) furnished 5-oxo-6-trifluoromethyl-2,3,5,6- tetrahydroimidazothiazoles and 5-oxo-2-phenyl-4-trifluoromethyl-4,5-dihydro-1 H-imidazoles.

Full text of DOI:10.1007/s11172-010-0062-y

Russian Chemical Bulletin, International Edition, Vol. 59, No. 1, pp. 197—199, January, 2010
197
Modification of biologically active amides
and amines with fluorineꢀcontaining heterocycles
2*. Nꢀ(2ꢀThienyl)imines on the base of methyl trifluoropyruvate
in cyclocondensation with 1,3ꢀN,Nꢀbinucleophiles
V. B. Sokolov and A. Yu. Aksinenko
Institute of Physiologically Active Substances, Russian Academy of Sciences,
1 Severnyi proezd, Chernogolovka, 142432 Moscow Region, Russian Federation, .
Fax: +7 (496) 524 9508. Eꢀmail: alaks@ipac.ac.ru
An approach to the modification of the biologically active compounds, substituted 2ꢀamiꢀ
nothiophenes, with fluorineꢀcontaining fiveꢀmembered heterocycles is proposed. The reaction
of 2ꢀaminothiophenes with methyl trifluoropyruvate yields the corresponding Nꢀ(2ꢀthiꢀ
enyl)imines, their subsequent cyclocondensation with 1,3ꢀN,Nꢀbinucleophiles (2ꢀaminothiꢀ
azoline and benzamidines) furnished 5ꢀoxoꢀ6ꢀtrifluoromethylꢀ2,3,5,6ꢀtetrahydroimidazothiꢀ
azoles and 5ꢀoxoꢀ2ꢀphenylꢀ4ꢀtrifluoromethylꢀ4,5ꢀdihydroꢀ1Нꢀimidazoles.
Key words: substituted 2ꢀaminothiophenes, methyl trifluoropyruvate, methyl (2ꢀthienylimiꢀ
no)ꢀ3,3,3ꢀtrifluoropropionate, 2ꢀaminothiazoline, benzamidines, 5ꢀoxoꢀ6ꢀtrifluoromethylꢀ
2,3,5,6ꢀtetrahydroimidazotriazoles, 5ꢀoxoꢀ2ꢀphenylꢀ4ꢀtrifluoromethylꢀ4,5ꢀdihydroꢀ1Нꢀimidꢀ
azoles, cyclocondensation.
Scheme 1
Substituted 2ꢀaminothiophenes, which can be synthesized
by the Gewald reaction,2,3 present a class of promising
biologically active compounds widely used in medicine
and agriculture.4—6 The main approaches to the molecular
design of 2ꢀaminothiophenes involve the introduction of subꢀ
stituents, including the trifluoromethyl group, in the
thiophene ring,7,8 incorporation of a 2ꢀaminothiophene
fragment into a heterocyclic system,9 modification of the
substituents at the amino group.10,11 The aim of the present
study was the modification of 2ꢀaminothiophenes with
fluorineꢀcontaining heterocycles. This conversion involved
the reaction of 2ꢀaminothiophenes 1 with methyl trifluoꢀ
ropyruvate (2) followed by cyclocondensations of the reꢀ
sulting 2ꢀ(2ꢀthienylimino)ꢀ3,3,3ꢀtrifluoropropionates 3
with 2ꢀaminothiazoline (4) or benzamidines 6. The preꢀ
mise of the present work was our data that have previously
been obtained in the study of cyclocondensations of
Nꢀsubstituted imines derived from methyl trifluoropyruꢀ
vate with 1,3ꢀbinucleophiles.12—15
The proposed procedure for the synthesis of hitherto
unknown 2ꢀthienylimines 3a—d involved successive addiꢀ
tion of equimolar amounts of pyridine, methyl trifluoropyꢀ
ruvate (2), and SOCl2 to a solution of 2ꢀaminothiophenes
1a—d (Scheme 1).
Imines 3a—d are crystalline solids. Their compositions
and the structures were determined based on the data from
1H and 19F NMR spectroscopy and elemental analysis.
1,3
R1R2
X
a
b
c
d
(CH2)3
C(O)OCH3
(CH2)4
CN
(CH2)4
C(O)OCH3
(CH2)5
CN
The 19F NMR spectra exhibited signals in the range
of δ 7—10 characteristic of Nꢀheterylimines derived from
methyl trifluoropyruvate.16
2ꢀThienylimines 3a—d reacted exothermally with fairꢀ
ly reactive 1,3ꢀbinucleophiles, such as 2ꢀaminothiazoline
(4) and benzamidines 6а—с following the cyclocondensaꢀ
tion pattern: 1,3ꢀbinucleoiphile adds to the C=N bond of
imine 3 with subsequent cyclization and elimination of
methanol. These conversions resulted in the correspondꢀ
ing 5ꢀoxoꢀ6ꢀtrifluoromethylꢀ2,3,5,6ꢀtetrahydroimidazoꢀ
[2,1ꢀb]thiazoles 5a—d and 5ꢀoxoꢀ2ꢀphenylꢀ4ꢀ(2ꢀthiꢀ
* For Part 1, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 193—195, January, 2010.
1066ꢀ5285/10/5901ꢀ0197 © 2010 Springer Science+Business Media, Inc.

198
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
Sokolov and Aksinenko
in benzene (50 mL), pyridine (7.8 g, 0.1 mol) and methyl trifluoꢀ
ropyruvate 2 (7.8 g, 0.1 mol) were successively added at 20 °С.
The reaction mixture was stirred for 30 min, then SOCl2 (6.0 g,
0.05 mol) was added and stirring was continued for 1 h. The
precipitate that formed was filtered off, the filtrate was concenꢀ
trated in vacuo, and the residue was recrystallized from hexane to
give compound 3a in a yield of 12.6 g (75%), m.p. 91—93 °С.
1Н NMR (CDCl3), δ: 2.42 (m, 2 Н, СН2); 2.97 (overlapping d, 4
H, СН2 + СН2, J = 7.7 Hz); 3.84 (s, 3 H, СН3O); 3.91 (s, 3 H,
СН3O). 19F NMR (CDCl3), δ: 6.97 s. Found (%): С, 46.75;
Н, 3.43; N, 4.01. C13H12F3NO4S. Calculated (%): С, 46.57;
Н, 3.61; N, 4.18.
enyl)aminoꢀ4ꢀtriflioromethylꢀ4,5ꢀdihydroꢀ1Нꢀimidazoles
7a—f (Scheme 2).
Scheme 2
Methyl 2ꢀ[(3ꢀcyanoꢀ4,5,6,7ꢀtetrahydrobenzo[b]thiophenꢀ2ꢀ
yl)imino]ꢀ3,3,3ꢀtrifluoropyruvate (3b) was synthesized as deꢀ
scribed for 3a in a yield of 11.7 g (74%), m.p. 79—81 °С. 1Н NMR
(CDCl3), δ: 1.93 (m, 4 H, CH2); 2.78 (m, 4 H, CH2); 4.01 (s, 3 H,
СН3O). 19F NMR (CDCl3), δ: 9.53 s. Found (%): С, 49.22;
Н, 3.38; N, 8.72. C13H11F3N2O2S. Calculated (%): С, 49.37;
Н, 3.51; N, 8.86.
Methyl 2ꢀ[(Z)ꢀ1ꢀmethoxycarbonylꢀ2,2,2ꢀtrifluoroethylideneꢀ
amino]ꢀ4,5,6,7ꢀtetrahydrobenzo[b]thiopheneꢀ3ꢀcarboxylate (3c)
was synthesized as described for 3а in a yield of 13.5 g (77%),
m.p. 86—88 °С. 1Н NMR (CDCl3), δ: 1.83 (m, 4 H, CH2); 2.74
(m, 4 H, CH2); 3.85 (s, 3 H, СН3O); 3.93 (s, 3 H, СН3O). 19F NMR
(DMSOꢀd6), δ: 8.99 s. Found (%): С, 48.27; Н, 4.16; N, 4.19.
C14H14F3NO4S. Calculated (%): С, 48.14; Н, 4.04; N, 4.01.
Methyl 2ꢀ[(3ꢀcyanoꢀ5,6,7,8ꢀtetrahydroꢀ4Нꢀcyclohepta[b]ꢀ
thiophenꢀ2ꢀyl)imino]ꢀ3,3,3ꢀtrifluoropyruvate (3d) was synthesized
as described for 3а in a yield of 12.1 g (73%), m.p. 68—69 °С.
1Н NMR (CDCl3), δ: 1.72 (m, 4 H, CH2); 1.92 (m, 2 H, CH2);
2.88 (m, 4 H, CH2); 4.00 (s, 3 H, СН3O). 19F NMR (DMSOꢀd6),
δ: 9.65 s. Found (%): С, 50.73; Н, 3.79; N, 8.31. C14H13F3N2O2S.
Calculated (%): С, 50.91; Н, 3.97; N, 8.48.
i. MeCN, 80 °С
Compound
5а, 7а
5b, 7b
5c, 7c,d
5d, 7e,f
R1R2
X
(CH2)3
(CH2)4
(CH2)4
(CH2)5
C(O)OMe
CN
C(O)OMe
CN
R3 = H (6а, 7b,c), CH2Ph (6b, 7a,d,e), CH2CH2Ph (6c, 7f)
Compounds 5 and 7 are crystalline solids. Their comꢀ
positions and the structures were established based on the
1
data from H and 19F NMR spectroscopy and elemental
Methyl 2ꢀ[(5ꢀoxoꢀ6ꢀtrifluoromethylꢀ2,3,5,6ꢀtetrahydroimiꢀ
dazo[2,1ꢀb]thiazolꢀ6ꢀyl)amino]ꢀ5,6ꢀdihydroꢀ4Нꢀcyclopenta[b]ꢀ
thiopheneꢀ3ꢀcarboxylate (5a). To a solution of imine 3а (3.35 g,
0.01 mol) in MeCN (20 mL), 2ꢀaminothiazoline 4 (1.02 g,
0.01 mol) was added. The reaction mixture was refluxed for 1 h
and poured into water (50 mL), the precipitate that formed was
recrystallized from 50% EtOH to give compound 5a in a yield of
analysis. The 19F NMR spectra showed the characteristic
signal in the range of δ 0.01—1.
In summary, hitherto unknown 2ꢀthienylimines deꢀ
rived from methyl trifluoropyruvate are promising reagents
for the synthesis of a variety of fluorineꢀcontaining Nꢀheꢀ
terylꢀsubstituted 2ꢀaminothiophenes. The proposed synꢀ
thetic approach to the modification of 2ꢀaminothiophenes
makes it possible to combine two biologically active fragꢀ
ments in one molecule, viz., 2ꢀaminothiophene and a hetꢀ
erocyclic moiety with a pharmacophoric 3,3,3ꢀtrifluoroꢀ
alanine fragment, which is known to possess the high bacꢀ
teriostatic activity.17
1
3.1 g (77%), m.p. 133—134 °С. Н NMR (DMSOꢀd6), δ: 2.34
(m, 2 H, CH2); 2.77 (m, 4 H, CH2); 3.82 (s, 3 H, СН3O); 3.86—4.06
(m, 4 H, CH2); 8.77 (s, 1 H, NH). 19F NMR (DMSOꢀd6), δ:
–0.43 s. Found (%): С, 44.26; Н, 3.26; N, 10.61. C15H14F3N3O3S2.
Calculated (%): С, 44.44; Н, 3.48; N, 10.36.
2ꢀ[(5ꢀOxoꢀ6ꢀtrifluoromethylꢀ2,3,5,6ꢀtetrahydroimidazoꢀ
[2,1ꢀb]thiazolꢀ6ꢀyl)amino]ꢀ4,5,6,7ꢀtetrahydrobenzo[b]thiophenꢀ
3ꢀcarbonitrile (5b) was synthesized as described for 5а in a yield
of 2.9 g (75%), m.p. 138—140 °С. 1Н NMR (DMSOꢀd6), δ: 1.79
(m, 4 H, CH2); 2.53 (m, 4 H, CH2); 3.87 (m, 4 H, CH2); 7.66
(s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: 0.89 s. Found (%):
С, 46.49; Н, 3.27; N, 14.33. C15H13F3N4OS2. Calculated (%):
С, 46.62; Н, 3.39; N, 14.50.
Methyl 2ꢀ[(5ꢀoxoꢀ6ꢀtrifluoromethylꢀ2,3,5,6ꢀtetrahydroimiꢀ
dazo[2,1ꢀb]thiazolꢀ6ꢀyl)amino]ꢀ4,5,6,7ꢀtetrahydrobenzo[b]ꢀ
thiopheneꢀ3ꢀcarboxylate (5c) was synthesized as described for 5а
in a yield of 3.0 g (72%), m.p. 128—129 °С. 1Н NMR (DMSOꢀd6),
δ: 1.77 (m, 4 H, CH2); 2.52 (m, 2 H, CH2); 2.68 (m, 2 H, CH2); 3.77
(s, 3 H, СН3O); 3.91 (m, 4 H, CH2); 9.14 (s, 1 H, NH). 19F NMR
(DMSOꢀd6), δ: 0.44 s. Found (%): С, 45.69; Н, 3.71; N, 10.15.
C16H16F3N3O3S2. Calculated (%): С, 45.82; Н, 3.84; N, 10.02.
Experimental
1
The H and 19F NMR spectra were recorded on a Bruker
DPX 200 instrument at 200.13 MHz and 188.29 MHz relative to tetꢀ
ramethylsilane (internal standard) and CF3COOH (external stanꢀ
dard), respectively. Melting points were determined in open
capillaries. The starting 2ꢀaminothiophene 1 was synthesized accorꢀ
ding to the known procedure,18 2ꢀaminothiazoline (4), benzꢀ
amidines 6, methyl trifluoropyruvate (2) were used as purchased
(Aldrich).
Methyl 2ꢀ[(Z)ꢀ1ꢀmethoxycarbonylꢀ2,2,2ꢀtrifluoroethylideneꢀ
amino]ꢀ5,6ꢀdihydroꢀ4Нꢀcyclopenta[b]thiopheneꢀ3ꢀcarboxylate
(3а). To a stirred solution of 2ꢀaminothiophene 1а (9.9 g, 0.05 mol)

Nꢀ(2ꢀThienyl)imines of methyl trifluoropyruvate
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 1, January, 2010
199
2ꢀ[(5ꢀOxoꢀ6ꢀtrifluoromethylꢀ2,3,5,6ꢀtetrahydroimidazoꢀ
[2,1ꢀb]thiazolꢀ6ꢀyl)amino]ꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀcycloheptaꢀ
[b]thiopheneꢀ3ꢀcarbonitrile (5d) was synthesized as described
1Н NMR (DMSOꢀd6), δ: 1.84 (m, 4 H, CH2); 2.01 (m, 2 H,
CH2); 2.86 (m, 6 H, CH2); 3.72—4.01 (t, 2 H, СН2, J = 7.6 Hz);
7.12 (m, 2 H, CHAr); 7.31 (m, 3 H, CHAr); 7.57 (s, 1 H, NH);
7.62—7.82 (m, 5 H, CHAr). 19F NMR (DMSOꢀd6), δ: 1.09 s.
Found (%): С, 64.19; Н, 4.63; N, 10.51. С28H25F3N4OS. Calcuꢀ
lated (%): С, 64.35; Н, 4.82; N, 10.72.
1
for 5а in a yield of 3.2 g (80%), m.p. 118—120 °С. Н NMR
(DMSOꢀd6), δ: 1.67 (m, 4 H, CH2); 1.84 (m, 2 H, CH2); 2.64
(m, 4 H, CH2); 3.72—4.02 (m, 4 H, CH2 + CH2); 7.45 (s, 1 H,
NH). 19F NMR (DMSOꢀd6), δ: 0.61 s. Found (%): С, 48.18;
Н, 3.61; N, 13.72. C16H15F3N4OS2. Calculated (%): С, 47.99;
Н, 3.78; N, 13.99.
This work was financially supported by Russian Acadꢀ
emy of Sciences (program «Medicinal and Biomedicinal
Chemistry» of the Division of Chemistry and Materials
Science) and the Russian Foundation for Basic Research
(Project 08ꢀ04ꢀ12074).
Methyl 2ꢀ[(1ꢀbenzylꢀ5ꢀoxoꢀ4ꢀtrifluoromethylꢀ2ꢀphenylꢀ4,5ꢀ
dihydroꢀ1Нꢀimidazolꢀ4ꢀyl)amino]ꢀ5,6ꢀdihydroꢀ4Нꢀcyclopentaꢀ
[b]thiopheneꢀ3ꢀcarboxylate (7a). To a solution of imine 3а
(3.35 g, 0.01 mol) in MeCN (20 mL), amidine 6a (2.1 g, 0.01 mol)
was added. The reaction mixture was refluxed of 1 h and poured
into water (50 mL), the precipitate that formed was recrystallized
from 50% EtOH to give compound 7a in a yield of 3.8 g (74%),
m.p. 192—194 °С.1Н NMR (DMSOꢀd6), δ: 2.35 (m, 2 Н, СН2);
2.80 (m, 4 H, СН2); 3.86 (s, 3 H, СН3O); 4.90 (АВꢀsystem, 2 Н,
CH2, J = 16.7); 7.00 (m, 2 H, CHAR); 7.26 (m, 3 H, CHAR);
7.4—7.78 (m, 5 H, CHAR); 8.86 (s, 1 H, NH). 19F NMR
(DMSOꢀd6), δ: 0.04 s. Found (%): С, 60.73; Н, 4.69; N, 8.31.
С26H22F3N3O3S. Calculated (%): С, 60.81; Н, 4.32; N, 8.18.
2ꢀ[(5ꢀOxoꢀ2ꢀphenylꢀ4ꢀtrifluoromethylꢀ4,5ꢀdihydroꢀ1Нꢀimiꢀ
dazolꢀ4ꢀyl)amino]ꢀ4,5,6,7ꢀtetrahydrobenzo[b]thiopheneꢀ3ꢀcarꢀ
bonitrile (7b) was synthesized as described for 7а in a yield of 3.1 g
(77%), m.p. 184—185 °С. 1Н NMR (DMSOꢀd6), δ: 1.79 (m, 4 H,
CH2); 2.53 (m, 4 H, CH2); 7.23 (s, 1 H, NH); 7.55 (m, 3 H, CHAr);
8.14 (d, 2 H, CHAr, J = 7.9 Hz); 12.38 (s, 1 H, NH). 19F NMR
(DMSOꢀd6), δ: 0.78 s. Found (%): С, 56.73; Н, 3.89; N, 13.61.
C19H15F3N4OS. Calculated (%): С, 56.43; Н, 3.74; N, 13.85.
Methyl 2ꢀ[(5ꢀoxoꢀ2ꢀphenylꢀ4ꢀtrifluoromethylꢀ4,5ꢀdihydroꢀ
1Нꢀimidazolꢀ4ꢀyl)amino]ꢀ4,5,6,7ꢀtetrahydrobenzo[b]thiopheneꢀ
3ꢀcarboxylate (7c) was synthesized as described for 7а in a yield
of 3.2 g (73%), m.p. 166—167 °С. 1Н NMR (DMSOꢀd6), δ: 1.74
(m, 4 H, CH2); 2.52 (m, 4 H, CH2); 3.83 (s, 3 H, СН3O); 7.61
(m, 3 H, CHAr); 8.18 (d, 2 H, CHAr, J = 7.9 Hz); 9.11 (s, 1 H,
NH); 12.53 (s, 1 H, NH). 19F NMR (DMSOꢀd6), δ: –0.41 s.
Found (%): С, 54.73; Н, 3.99; N, 9.34. C20H18F3N3O3S. Calcuꢀ
lated (%): С, 54.92; Н, 4.15; N, 9.61.
References
1. V. B. Sokolov, A. Yu. Aksinenko, T. A. Epishina, T. V. Goreꢀ
va, Izv. Akad. Nauk, Ser. Khim., 2009, 614 [Russ. Chem.
Bull., Int. Ed., 2009, 58, No. 12].
2. K. Gewald, Chem. Ber., 1965, 98, 3571.
3. R. W. Sabnis, D. W. Rangnekar, N. D. Sonawane, J. Heteroꢀ
cycl. Chem., 1999, 36, 333.
4. H. LuEtjens, A. Zickgraft, H. Figler, J. Linden, R. A. Olsson,
P. J. Scammels, J. Med. Chem., 2003, 46, 1870.
5. G. Nikolakopoulos, H. Figler, J. Linden, P. Scammels,
J. Bioorg. Med. Chem., 2006, 14, 2358.
6. A. D. Pillai, S. Rani, P. R. Rathod, F. P. Xavier, K. K. Vasu,
H. Padh, V. Sudarsanam, Bioorg. Med. Chem., 2005, 13, 1275.
7. L. Aurelio, H. Figler, B. L. Flynn, J. Linden, P. J. Scamꢀ
mells, Bioorg. Med. Chem., 2008, 16, 1319.
8. P. G. Baraldi, M. G. Pavani, J. C. Shryock, A. R. Moorman,
V. Iannotta, P. A. Borea, R. Romagnoli, Europ. J. Med. Chem,
2004, 39, 855.
9. A. Davoodnia, H. Behmadi, A. Zare Bidaki, M. Bakavoli,
N. Tavakoli Hoseini, Chinese Chem. Lett., 2007, 18, 1163.
10. R. J. Patch, C. A. Baumann, J. Liu, A. C. Gibbs, H. Ott,
J. Lattanze, M. R. Player, Bioorg. Med. Chem. Lett., 2006,
16, 3282.
11. Yu. Gui Gu, A. S. Florjanic, R. F. Clark, T. Zhang, C. S.
Cooper, D. D. Anderson, C. G. Lerner, J. O. McCall, Y. Cai,
C. L. BlackꢀSchaefer, G. F. Stamper, P. J. Hajduk, B. A.
Beutel, Bioorg. Med. Chem. Lett., 2004, 14, 267.
12. V. B. Sokolov, A. Yu. Aksinenko, T. A. Epishina, T. V. Goreꢀ
va, I. V. Martynov, Izv. Akad. Nauk, Ser. Khim., 2005, 462
[Russ. Chem. Bull., Int. Ed., 2005, 54, 472].
13. V. B. Sokolov, A. Yu. Aksinenko, T. A. Epishina, T. V. Goreꢀ
va, A. N. Pushin, I. V. Martynov, Izv. Akad. Nauk, Ser. Khim.,
2005, 1619 [Russ. Chem. Bull., Int. Ed., 2005, 54, 1667].
14. V. B. Sokolov, A. Yu. Aksinenko, Izv. Akad. Nauk, Ser. Khim.,
2007, 2176 [Russ. Chem. Bull., Int. Ed., 2007, 54, 2252].
15. V. B. Sokolov, A. Yu. Aksinenko, I. V. Martynov, Izv. Akad.
Nauk, Ser. Khim., 2007, 2171 [Russ. Chem. Bull., Int. Ed.,
2007, 54, 2247].
Methyl 2ꢀ[(1ꢀbenzylꢀ5ꢀoxoꢀ2ꢀphenylꢀ4ꢀtrifluoromethylꢀ4,5ꢀ
dihydroꢀ1Нꢀimidazolꢀ4ꢀyl)amino]ꢀ4,5,6,7ꢀtetrahydrobenzo[b]ꢀ
thiopheneꢀ3ꢀcarboxylate (7d) was synthesized as described for 7а
in a yield of 3.7 g (70%), m.p. 118—119 °С. 1Н NMR (DMSOꢀd6),
δ: 1.74 (m, 4 H, CH2); 2.49 (m, 2 H, CH2); 2.66 (m, 2 H, CH2);
3.77 (s, 3 H, СН3O); 4.85 (ABꢀsystem, 2 H, CH2, J = 11.2 Hz);
6.96 (m, 2 H, CHAR); 7.22 (m, 3 H, CHAR); 7.49 (m, 2 H,
CHAR); 7.63 (m, 3 H, CHAR); 9.16 (s, 1 H, NH). 19F NMR
(DMSOꢀd6), δ: 0.77 s. Found (%): С, 61.71; Н, 4.79; N, 8.21.
С27H24F3N3O3S. Calculated (%): С, 61.47; Н, 4.59; N, 7.96.
2ꢀ[(1ꢀBenzylꢀ5ꢀoxoꢀ2ꢀphenylꢀ4ꢀtrifluoromethylꢀ4,5ꢀdihyꢀ
droꢀ1Нꢀimidazolꢀ4ꢀyl)amino]ꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀcyclohepꢀ
ta[b]thiopheneꢀ3ꢀcarbonitrile (7e) was synthesized as described
1
for 7а in a yield of 3.5 g (69%), m.p. 123—124 °С. Н NMR
16. V. B. Sokolov, A. Yu. Aksinenko, I. V. Martynov, Izv. Akad.
Nauk, Ser. Khim., 2005, 460 [Russ. Chem. Bull., Int. Ed.,
2005, 54, 470].
17. C. W. Fearon, J. A. Rodkey, R.H. Abeles, Biochemistry, 1982,
21, 3790.
(DMSOꢀd6), δ: 1.70 (m, 4 H, CH2); 1.87 (m, 2 H, CH2); 2.68
(m, 4 H, CH2); 4.84 (s, 2 H, СН2); 6.98 (m, 2 H, CHAr); 7.24 (m, 3 H,
CHAr), 7.41—7.68 (m, 6 H, CHAr + NH). Спектр 19F NMR
(DMSOꢀd6), δ: 0.91 s. Found (%): С, 63.58; Н, 4.79; N, 11.27.
С27H23F3N4OS. Calculated (%): С, 63.77; Н, 4.56; N, 11.02.
2ꢀ[(5ꢀOxoꢀ1ꢀphenethylꢀ2ꢀphenylꢀ4ꢀtrifluoromethylꢀ4,5ꢀdiꢀ
hydroꢀ1Нꢀimidazolꢀ4ꢀyl)amino]ꢀ5,6,7,8ꢀtetrahydroꢀ4Hꢀcycloꢀ
hepta[b]thiopheneꢀ3ꢀcarbonitrile (7f) was synthesized as deꢀ
scribed for 7а in a yield of 3.7 g (71%), m.p. 120—121 °С.
18. K. Gewald, E. Schinke, H. Bottcher, Chem. Ber., 1966, 99, 94.
Received June 18, 2009,
in revised form October13, 2009