Synthesis of substituted pyrido[3′,2′:4,5]thieno[3,2-c]isoquinolin-5(6H)-ones and their sulfinyl and sulfonyl derivatives

Article abstract of DOI:10.1007/s11172-017-1766-z

A method for the synthesis of previously unknown pyrido[3′,2′:4,5]thieno[3,2-c]isoquinolin-5(6H)-ones was suggested, which includes a condensation reaction of substituted 3-cyanopyridine-2(1H)-thiones with methyl 2-(chloromethyl)benzoate and subsequent treatment of the condensation products with potassium tert-butoxide. The oxidation of the condensation products to sulfoxides or sulfones and subsequent treatment of these compounds with potassium tert-butoxide led to substituted pyrido[3′,2′:4,5]thieno[3,2-c]isoquinolin-5(6H)-one 11-oxides or substituted pyrido[3′,2′:4,5]thieno[3,2-c]isoquinolin-5(6H)-one 11,11-dioxides.

Full text of DOI:10.1007/s11172-017-1766-z

Russian Chemical Bulletin, International Edition, Vol. 66, No.3, pp. 523—530, March, 2017
523
Synthesis of substituted pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ
5(6H)ꢀones and their sulfinyl and sulfonyl derivatives
V. E. Kalugin and A. M. Shestopalov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 952 5308. Eꢀmail: vek@ioc.ac.ru
A method for the synthesis of previously unknown pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ
5(6H)ꢀones was suggested, which includes a condensation reaction of substituted 3ꢀcyanopyriꢀ
dineꢀ2(1H)ꢀthiones with methyl 2ꢀ(chloromethyl)benzoate and subsequent treatment of the
condensation products with potassium tertꢀbutoxide. The oxidation of the condensation prodꢀ
ucts to sulfoxides or sulfones and subsequent treatment of these compounds with potassium
tertꢀbutoxide led to substituted pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀone 11ꢀoxides
or substituted pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀone 11,11ꢀdioxides.
Key words: 3ꢀcyanopyridineꢀ2(1H)ꢀthiones, methyl 2ꢀ(chloromethyl)benzoate, potassium
tertꢀbutoxide, domino reactions, pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀones,
pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀone 11ꢀoxides, pyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone 11,11ꢀdioxides.
Derivatives of fused isoquinolines are of practical inꢀ
terest due to the presence of different kinds of pharmaꢀ
cological activity.1—4
upon reflux, which gave substituted 3ꢀcyanoꢀ2ꢀ[(2ꢀ(methꢀ
oxycarbonyl)benzyl)thio]pyridines 3a—f in good or very
good yields. The reaction of sulfides 3a—f with 1.5 equiv.
of potassium tertꢀbutoxide in DMF leads to the formation
of good yields of substituted pyrido[3´,2´:4,5]thienoꢀ
[3,2ꢀc]isoquinolinꢀ5(6H)ꢀones 4a—f (Scheme 1).
It seemed interesting to study a possibility of the synꢀ
thesis of pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀ
one derivatives containing an oxidized sulfur atom through
the oxidation of sulfides 3 to the corresponding sulfoxides
or sulfones and subsequent treatment of the thus obtained
compounds with potassium tertꢀbutoxide, as it was made
for benzothieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀone derivatives.7
Thus, the oxidation of sulfides 3a—f with 30% aqueous
H2O2 in AcOH at 60—65 °C leads to the formation of
sulfoxides 5a—f in good yields. The oxidation of sulfides
3a—f carried out with KMnO4 in AcOH at room temperaꢀ
ture gave sulfones 7a—f in very good yields.
The reaction of sulfoxides 5a—f with potassium tertꢀ
butoxide was carried out under conditions described for
sulfides 3a—f, however, a somewhat longer time is requirꢀ
ed for the reaction to reach completion. In this case, if the
reaction of compounds 5a,b with potassium tertꢀbutoxide
proceeds smoothly and leads to the corresponding pyridoꢀ
[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀone 11ꢀoxides
6a,b in good yields (52% and 65%, respectively), a similar
reaction of sulfoxides 5c—f containing aryl substituents was
accompanied by the formation of side products and not
very high yields of the target compounds 6c—f (21—28%).
Conversely, the reaction of sulfones 7a—f with potassium tertꢀ
As a part of our studies on the synthesis of fused isoꢀ
quinolines, we have developed a versatile method for the
synthesis of this family of heterocycles, which consists in
the alkylation reaction of nitrile derivatives containing
a hydroxy or a thiol group next to the nitrile function with
2ꢀ(chloromethyl)benzoic acid ester or nitrile. Subseꢀ
quent treatment of the alkylation product with potassium
tertꢀbutoxide triggers a domino reaction including the
Thorpe—Ziegler and Thorpe—Guareschi reactions for the
products of alkylation with 2ꢀ(chloromethyl)benzoic acid
ester or the Thorpe—Ziegler and heteroꢀThorpe—Ziegler
domino reactions for the products of alkylation with
2ꢀ(chloromethyl)benzonitrile, both resulting in the forꢀ
mation of the target heterocycles. Such types of domino
reactions are described in detail in the literature.5 Using
this synthetic approach, we synthesized benzofuro[3,2ꢀc]ꢀ
isoquinoline,6 benzothieno[3,2ꢀc]isoquinoline,7,8 and
pyrido[3´,2´:4,5]furo[3,2ꢀc]isoquinoline9 derivatives. The
present study is devoted to the synthesis of derivatives of
a new heterocyclic system of pyrido[3´,2´:4,5]thienoꢀ
[3,2ꢀc]isoquinoline, namely, substituted pyrido[3´,2´:4,5]ꢀ
thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀones using substituted
3ꢀcyanopyridineꢀ2(1H)ꢀthiones and methyl 2ꢀ(chloroꢀ
methyl)benzoate as the starting compounds.
The reaction of substituted 3ꢀcyanopyridineꢀ2(1H)ꢀ
thiones 1a—f with methyl 2ꢀ(chloromethyl)benzoate 2 was
carried out in the presence of Et3N in solution of CHCl3
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 0523—0530, March, 2017.
1066ꢀ5285/17/6603ꢀ0523 © 2017 Springer Science+Business Media, Inc.

524
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
Kalugin and Shestopalov
Scheme 1
butoxide proceeded smoothly in all the cases and gave the
corresponding pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ
5(6H)ꢀone 11,11ꢀdioxides 8a—f in good yields (Scheme 2).
The structure of compounds 3a—f—8a—f was conꢀ
firmed by IR spectroscopy, 1H and 13C NMR data, as well
as by elemental analysis. The IR spectra of compounds
3a—f, 5a—f, and 7a—f are characterized by the presence
of the absorption bands of the CN group in the region of
2216—2236 cm–1 and of the ester C=O group in the reꢀ
gion of 1700—1720 cm–1. The absorption bands of
the S=O group in sulfoxides 5a—f are in the region of
1044—1080 cm–1. In sulfones 7a—f, the SO2 group have
two absorption bands in the regions 1320—1340 and
1
1120—1148 cm–1. The H NMR spectra of 3a—f, 5a—f,
and 7a—f exhibit a signal for the protons of the ester OCH3
group as a singlet in the region of δ 3.66—3.88. In the
1H NMR spectra of sulfides 3a—f, the signals for the proꢀ
tons of the CH2S group are found as a singlet in the region
of δ 4.81—5.06. The signals for the protons of the CH2S(O)
group in sulfoxides 5a—f were found as two doublets in the
regions of δ 4.79—4.98 and 4.88—5.06 with the spinꢀspin
coupling constants J = 11.9 Hz for 5a and 12.4 Hz for
other sulfoxides. The signal for the protons of the CH2SO2
group in sulfones 7a—f was found as a singlet in the region
of δ 5.41—5.46. The 13C NMR spectra of compounds
3a—f, 5a—f, and 7a—f exhibit signals for the carbon atoms
of the ester OCH3 group in the region of δ 52.03—52.29.
The signal for the carbon atom of the CN group has
a chemical shift at δ 110.30—115.57, while a signal for the
carbon atom of the ester C=O group at δ 166.60—166.94.
1, 3, 4
R1
Me
H
Ph
Ph
Ph
CF3
R2
H
R2—R3
(CH2)4
R3
Me
a
b
c
d
e
f
H
H
H
H
Ph
4ꢀBrC6H4
2ꢀThienyl
Ph
Reaction conditions: i. Et3N (1.4 equiv.), CHCl3, reflux, 40 min;
ii. ButOK (1.5 equiv.), DMF, 55—60 °C, 30 min.
Scheme 2
5—8
R1
Me
H
R2
H
R2—R3
(CH2)4
R3
Me
5—8
R1
Ph
Ph
R2
H
H
R3
a
b
c
d
e
f
4ꢀBrC6H4
2ꢀThienyl
Ph
Ph
H
Ph
CF3
H
Reaction conditions: i. AcOH, 30% H2O2, 60—65 °C, 2—3 h; ii. AcOH, KMnO4, 20—25 °C, 40 min; iii. ButOK (1.5 equiv.), DMF,
55—60 °C, 1 h; iv. ButOK (1.5 equiv.), DMF, 55—60 °C, 30 min.

Benzothieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
525
Scheme 3
n = 0 (3a—f, 4a—f, 9a—f), 1 (5a—f, 6a—f, 10a—f), 2 (7a—f, 8a—f, 11a—f)
1
pellets. H (300 MHz) and 13C NMR spectra (75 MHz) were
recorded on a Bruker Avanceꢀ300 spectrometer in solution of
DMSOꢀd6, using tetramethylsilane as an internal standard. Eleꢀ
mental microanalysis was carried out on a Perkin—Elmer 2400
CHN analyzer.
Apart from that, sulfides 3a—f are characterized by the
presence of a signal for the carbon atom of the CH2S
group at δ 31.97—32.75, in sulfoxides 5a—f a signal for the
carbon atom of the CH2S(O) group has a chemical shift at
δ 57.72—57.88, while for sulfone 7a—f a signal for the
carbon atom of the CH2SO2 group has a chemical shift at
δ 54.63—55.50
The IR spectra of the target products 4a—f, 6a—f, and
8a—f are characterized by the presence of the absorption
bands in the regions of 3227—3484 cm–1 for the NH group
and 1636—1692 cm–1 for the C=O group. In the IR specꢀ
tra of sulfoxides 6a—f, the absorption bands of the S=O
group are in the region of 1040—1079 cm–1. The sulfonyl
group in heterocycles 8a—c has two absorption bands in
the regions of 1308—1325 and 1128—1152 cm–1. The
1H NMR spectra of compounds 4a—f, 6a—f, and 8a—f
have a signal for the proton of the NH group as a broad
singlet at δ 10.53—12.76, while in the 13C NMR spectra
the signal for the carbon atom of the C=O group is found
at δ 161.22—164.58.
We believe that the reactions of sulfides 3a—f, sulfoxꢀ
ides 5a—f, and sulfones 7a—f with potassium tertꢀbutoxꢀ
ide follow the same mechanism, which is a domino reacꢀ
tion including in the first step the formation of the correꢀ
sponding benzothiophene intermediates 9a—f, 10a—f, and
11a—f by the Thorpe—Ziegler reaction and in the second
step their annulation to compounds 4a—f, 6a—f, and 8a—f
by the Thorpe—Guareschi reaction (Scheme 3).
In conclusion, we synthesized new pyrido[3´,2´:4,5]ꢀ
thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀones in good yields by the
alkylation of substituted 2ꢀmercaptonitriles with methyl
2ꢀ(chloromethyl)benzoate and subsequent reaction of the
alkylation products with potassium tertꢀbutoxide. The oxidꢀ
ation of the alkylation products to the corresponding sulfꢀ
oxides and sulfones with subsequent treatment of these
compounds with potassium tertꢀbutoxide allowed us to
obtain pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀ
one derivatives containing an oxidized sulfur atom.
Synthesis starting compounds. 3ꢀCyanopyridineꢀ2(1H)ꢀ
thiones 1a,10 1b,11 and 1f12 and methyl 2ꢀ(chloromethyl)ꢀ
benzoate 213 were obtained according to the procedures described
in the literature. Compound 1d was obtained according to
a modified procedure described in the work.14
6ꢀ(4ꢀBromophenyl)ꢀ3ꢀcyanoꢀ4ꢀphenylpyridineꢀ2(1H)ꢀthione
(1d). A mixture of 4ꢀbromochalcone15 (8.61 g, 30 mmol) and
malononitrile (2.64 g, 40 mmol) was dissolved in EtOH (40 mL)
with heating. Few drops of Et3N were added to the solution. The
reaction mixture was allowed to cool down to room temperature
and after 4 h, the crystals formed were collected by filtration,
washed with cold ethanol and dried to obtain an adduct of maloꢀ
nonitrile with 4ꢀbromochalcone (8.05 g, 76%), m.p. 122—124 °C
(EtOH), which was used without further purification.
Powdered sulfur (0.7 g, 22 mmol) was added to a solution of
piperidine (2.55 g, 30 mmol) in EtOH (50 mL). The reaction
mixture was refluxed for 20 min, followed by the addition of the
adduct of malononitrile with 4ꢀbromochalcone (7.06 g, 20 mmol)
obtained earlier and the reflux for another 2 h. Then, AcOH (2.4 g,
40 mmol) was added and the mixture was cooled to 0 °C. The
crystals formed were collected by filtration, washed with cold
EtOH, and dried to obtain 1d (5.2 g, 71%), m.p. 218—220 °C
(DMF—MeOH). Found (%): C, 59.02; H, 3.17; N, 7.55; Br, 21.43;
S, 8.61. C18H11BrN2S. Calculated (%): C, 58.87; H, 3.02;
N, 7.63; Br, 21.76; S, 8.73. IR (KBr, ν/cm–1): 3432 (NH), 2872,
2224 (CN), 1608, 1548, 1208, 816. 1H NMR (DMSOꢀd6), δ: 7.23
(br.s, 1 H, HPy(5)); 7.60 (m, 3 H, H4ꢀPh(3), H4ꢀPh(4), H4ꢀPh(5));
7.72 (m, 4 H, H4ꢀPh(2), H4ꢀPh(6), H6ꢀPh(2), H6ꢀPh6)); 7.92 (d, 2 H,
H6ꢀPh(3), H6ꢀPh(5), J = 8.1 Hz); 14.13 (br.s, 1 H, NH).
Compounds 1c and 1e were obtained similarly.
3ꢀCyanoꢀ4,6ꢀdiphenylpyridineꢀ2(1H)ꢀthione (1c). The yield
was 70%, m.p. 227—229 °C (DMF—MeOH; cf. Ref. 14: m.p.
227—229 °C).
3ꢀCyanoꢀ4ꢀphenylꢀ6ꢀ(2ꢀthienyl)pyridineꢀ2(1H)ꢀthione (1e).
The yield was 74%, m.p. 227—229 °C (DMF—MeOH; cf.
Ref. 16: m.p. 228—230 °C).
Synthesis of substituted 3ꢀcyanoꢀ2ꢀ{[2ꢀ(methoxycarbonꢀ
yl)benzyl]thio}pyridines 3a—f (general procedure). Triethylamine
(1 mL, 7 mmol) and methyl 2ꢀ(chloromethyl)benzoate 2 (0.92 g,
5 mmol) were added to a suspension of 3ꢀcyanopyridineꢀ2(1H)ꢀ
thione 1a—f (5 mmol) in CHCl3 (6 mL). The reaction mixture
was refluxed for 30 min, then the solvent was evaporated in vacuo
and the product was isolated by column chromatography (silica
Experimental
Melting points were measured on a Kofler heating block. IR
spectra were recorded on a Specord M82 spectrometer in KBr

526
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
Kalugin and Shestopalov
gel 60—80 mesh, eluent hexane—CHCl3 = 3 : 2, 1 : 1) and crysꢀ
tallized from an appropriate solvent.
130.67, 131.00, 131.98, 132.57, 135.51, 135.85, 138.75, 154.52,
156.83, 162.44, 166.93 (C=O).
3ꢀCyanoꢀ4,6ꢀdimethylꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]thio}ꢀ
pyridine (3a). The yield was 74%, m.p. 101—103 °C (MeOH).
Found (%): C, 65.51; H, 5.07; N, 9.05; S, 10.18. C17H16N2O2S.
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]thio}ꢀ4ꢀphenylꢀ6ꢀ
(2ꢀthienyl)pyridine (3e). The yield was 76%, m.p. 163—165 °C
(CHCl3—MeOH). Found (%): C, 67.62; H, 3.96; N, 6.21;
S, 14.38. C25H18N2O2S2. Calculated (%): C, 67.85; H, 4.10;
N, 6.33; S, 14.49. IR, ν/cm–1: 2956, 2212 (CN); 1712 (C=O); 1568,
Calculated (%): C, 65.36; H, 5.16; N, 8.97; S, 10.26. IR, ν/cm–1
:
3008, 2956, 2216 (CN), 1716 (C=O), 1580, 1432, 1292, 1264,
1
1
1076, 716. H NMR (DMSOꢀd6), δ: 2.34 (s, 3 H, 4ꢀMe); 2.52
1520, 1432, 1076, 700. H NMR (DMSOꢀd6), δ: 3.88 (s, 3 H,
(s, 3 H, 6ꢀMe); 3.86 (s, 3 H, OMe); 4.82 (s, 2 H, CH2S); 7.05
(s, 1 H, HPy(5)); 7.38 (t, 1 H, HBz(4)*, J = 7.3 Hz); 7.52 (t, 1 H,
HBz(5), J = 7.3 Hz); 7.64 (d, 1 H, HBz(3), J = 8.1 Hz); 7.87 (d, 1 H,
HBz(6), J = 7.3 Hz). 13C NMR (DMSOꢀd6), δ: 19.54 (4ꢀMe);
24.19 (6ꢀMe); 31.69 (CH2S); 52.14 (OMe); 103.59 (CCN);
114.87 (CN); 120.35, 127.63, 128.87, 130.46, 131.48, 132.29,
139.41, 152.51, 160.48, 161.26, 166.91 (C=O).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]thio}ꢀ5,6,7,8ꢀtetraꢀ
hydroquinoline (3b). The yield was 78%, m.p. 188—190 °C
(CHCl3—MeOH). Found (%): C, 67.61; H, 5.44; N, 8.32; S, 9.58.
C19H18N2O2S. Calculated (%): C, 67.43; H, 5.36; N, 8.28;
S, 9.47. IR, ν/cm–1: 2932, 2220 (CN), 1716 (C=O), 1536, 1388,
1132, 1076, 716. 1H NMR (DMSOꢀd6), δ: 1.74 (m, 2 H, C(6)H2);
1.84 (m, 2 H, C(7)H2); 2.69 (t, 2 H, C(5)H2, J = 5.9 Hz); 2.92
(t, 2 H, C(8)H2, J = 5.9 Hz); 3.86 (s, 3 H, OMe); 4.81 (s, 2 H,
CH2S); 7.38 (t, 1 H, HBz(4), J = 7.3 Hz); 7.52 (t, 1 H, HBz(5),
J = 7.3 Hz); 7.62 (d, 1 H, HBz(3), J = 7.3 Hz); 7.83 (s, 1 H, H(4)
of tetrahydroquinoline); 7.87 (d, 1 H, HBz(6), J = 7.3 Hz). 13C NMR
(DMSOꢀd6), δ: 21.60 (C(6)H2); 21.89 (C(7)H2); 26.87 (C(5)H2);
31.64 (CH2S); 32.25 (C(8)H2); 52.16 (OMe); 103.06 (CCN);
115.75 (CN); 127.63, 128.56, 128.88, 130.47, 131.53, 132.31,
139.50, 141.84, 156.77, 161.48, 166.93 (C=O).
OMe); 4.99 (s, 2 H, CH2S); 7.27 (t, 1 H, Hthph(4)*, J = 4.4 Hz);
7.41 (t, 1 H, HBz(4)); 7.53 (t, 1 H, HBz(5), J = 8.1 Hz); 7.55
(m, 3 H, H4ꢀPh(3), H4ꢀPh(4), H4ꢀPh(5)); 7.68 (m, 2 H, H4ꢀPh(2),
H4ꢀPh(6)); 7.77 (d, 1 H, HBz(3), J = 7.3 Hz); 7.88 (m, 2 H,
Hthph(3), HPy(5)); 7.94 (d, 1 H, HBz(6), J = 7.3 Hz); 8.15 (d, 1 H,
Hthph(5), J = 2.9 Hz). 13C NMR (DMSOꢀd6), δ: 31.97 (CH2S);
52.23 (OMe); 101.91 (CCN); 114.58, 115.49 (CN); 127.90,
128.54, 128.70, 128.74 (d, J= 2.2 Hz); 128.78, 129.13 (d, J= 3.3 Hz);
130.06, 130.78, 130.81 (d, J = 2.2 Hz); 131.64, 132.63, 135.50,
139.35, 142.47, 153.49, 154.26, 162.29, 166.86 (C=O).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]thio}ꢀ6ꢀphenylꢀ4ꢀ
(trifluoromethyl)pyridine (3f). The yield was 74%, m.p. 126—127 °C
(CHCl3—MeOH). Found (%): C, 61.51; H, 3.61; N, 6.37;
S, 7.64. C22H15F3N2O2S. Calculated (%): C, 61.68; H, 3.53;
N, 6.54; S, 7.48. IR, ν/cm–1: 3032, 2958, 2228 (CN); 1716 (C=O);
1580, 1548, 1372, 1276, 1260, 1080, 720. 1H NMR (DMSOꢀd6),
δ: 3.85 (s, 3 H, OMe); 5.05 (s, 2 H, CH2S); 7.41 (t, 1 H, HBz(4),
J = 7.3 Hz); 7.49 (t, 1 H, HBz(5), J = 7.3 Hz); 7.58—7.66 (m, 4 H,
HBz(3), H6ꢀPh(3), H6ꢀPh(4), H6ꢀPh(5)); 7.92 (d, 1 H, HBz(6),
J = 7.3 Hz); 8.19 (s, 1 H, HPy(5)); 8.29 (m, 2 H, H6ꢀPh(2), H6ꢀPh(6)).
13C NMR (DMSOꢀd6), δ: 32.75 (CH2S); 52.29 (OMe); 99.59
(CCN); 112,70 (CN); 112.77 (t, J = 4.6 Hz); 121.42 (q, CF3,
J = 276.2 Hz); 127.97, 128.05, 128.90, 129.22, 130.75, 131.00,
131.81, 132.65, 135.64, 138.24, 141.43 (q, CCF3, J = 33.2 Hz);
159.79, 164.13, 166.90 (C=O).
Synthesis of substituted pyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀones 4a—f (general procedure). Potassium
tertꢀbutoxide (0.51 g, 4.5 mmol) was added to a solution of comꢀ
pound 3a—f (3 mmol) in anhydrous DMF (5 mL). The reaction
mixture was stirred at 55—60 °C for 30 min and then poured into
H2O (40 mL). Acetic acid (0.4 mL) was added to the obtained
mixture, the crystals formed were collected by filtration, dried,
and crystallized from an appropriate solvent.
7,9ꢀDimethylpyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀ
one (4a). The yield was 85%, m.p. > 330 °C (decomp.) (DMF—
MeOH). Found (%): C, 68.69; H, 4.43; N, 9.86; S, 11.38.
C16H12N2OS. Calculated (%): C, 68.55; H, 4.31; N, 9.99; S, 11.44.
IR, ν/cm–1: 3256 (NH); 3032, 2972, 1644 (C=O); 1608, 1560,
1456, 1372, 1144, 868, 720. 1H NMR (DMSOꢀd6), δ: 2.58 (s, 3 H,
7ꢀMe); 2.93 (s, 3 H, 9ꢀMe); 7.17 (s, 1 H, HPTI(8))**; 7.62 (t, 1 H,
HPTI(2), J = 8.1 Hz); 7.85 (m, 2 H, HPTI(1), HPTI(3)); 8.36 (d, 1 H,
HPTI(4), J = 7.3 Hz); 10.53 (br.s, 1 H, NH).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]thio}ꢀ4,6ꢀdiphenylꢀ
pyridine (3c). The yield was 86%, m.p. 171—173 °C (CHCl3—
MeOH). Found (%): C, 74.11; H, 4.70; N, 6.31; S, 7.41.
C27H20N2O2S. Calculated (%): C, 74.29; H, 4.62; N, 6.42;
S, 7.34. IR, ν/cm–1: 3064, 2212 (CN), 1716 (C=O), 1568, 1528,
1
1268, 1132, 748, 728. H NMR (DMSOꢀd6), δ: 3.86 (s, 3 H,
OMe); 5.06 (s, 2 H, CH2S); 7.41 (t, 1 H, HBz(4), J = 7.3 Hz);
7.46—7.62 (m, 7 H, HBz(5), H6ꢀPh(3), H6ꢀPh(4), H6ꢀPh(5),
H4ꢀPh(3), H4ꢀPh(4), H4ꢀPh(5)); 7.66 (d, 1 H, HBz(3), J = 7.3 Hz);
7.73 (m, 2 H, H4ꢀPh(2), H4ꢀPh(6)); 7.90 (s, 1 H, HPy(5)); 7.93
(d, 1 H, HBz(6), J = 7.3 Hz); 8.29 (m, 2 H, H6ꢀPh(2), H6ꢀPh(6)).
13C NMR (DMSOꢀd6), δ: 32.28 (CH2S); 52.21 (OMe); 102.73
(CCN), 115.51 (CN), 116.41, 127.54, 127.81, 128.63, 128.80,
128.90, 128.99, 130.06, 130.64, 130.80, 130.92, 132.51, 135.63,
136.66, 138.86, 154.39, 157.98, 162.31, 166.92 (C=O).
6ꢀ(4ꢀBromophenyl)ꢀ3ꢀcyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzꢀ
yl]thio}ꢀ4ꢀphenylpyridine (3d). The yield was 84%, m.p. 168—170 °C
(CHCl3—MeOH). Found (%): C, 62.77; H, 3.65; N, 5.35;
Br, 15.32; S, 6.15. C27H19BrN2O2S. Calculated (%): C, 62.92;
H, 3.72; N, 5.44; Br, 15.50; S, 6.22. IR, ν/cm–1: 2948, 2216
(CN), 1720 (C=O), 1568, 1524, 1260, 1076, 832, 756, 696.
1H NMR (DMSOꢀd6), δ: 3.86 (s, 3 H, OMe); 5.03 (s, 2 H, CH2S);
7.41 (t, 1 H, HBz(4), J = 7.3 Hz); 7.51 (t, 1 H, HBz(5), J = 7.3 Hz);
7.58 (m, 3 H, H4ꢀPh(3), H4ꢀPh(4), H4ꢀPh(5)); 7.64 (d, 1 H, HBz(3),
J = 8.1 Hz); 7.72 (m, 2 H, H4ꢀPh(2), H4ꢀPh(6)); 7.76 (d, 2 H,
H6ꢀPh(3), H6ꢀPh(5), J = 8.8 Hz); 7.92 (m, 2 H, HPy(5), HBz(6)); 8.24
(d, 2 H, H6ꢀPh(2), H6ꢀPh(6), J = 8.8 Hz). 13C NMR (DMSOꢀd6),
δ: 32.35 (CH2S); 52.25 (OMe); 103.04 (CCN); 115.46 (CN);
116.49, 124.68, 127.87, 128.67, 128.81, 129.01, 129.57, 130.14,
8,9,10,11ꢀTetrahydroisoquinolino[3´,4´:4,5]thieno[2,3ꢀb]ꢀ
quinolinꢀ5(6H)ꢀone (4b). The yield was 82%, m.p. >330 °C
(DMF—MeOH). Found (%): C, 70.41; H, 4.53; N, 9.23; S, 10.57.
C18H14N2OS. Calculated (%): C, 70.56; H, 4.61; N, 9.14;
S, 10.46. IR, ν/cm–1: 3306 (NH); 3032, 2932, 1652 (C=O);
1
1608, 1552, 1524, 1392, 1156, 764. H NMR (DMSOꢀd6), δ:
1.84 (m, 4 H, C(9)H2, C(10)H2); 2.88 (t, 2 H, C(8)H2, J = 5.9 Hz);
2.98 (t, 2 H, C(11)H2, J = 5.9 Hz); 7.59 (t, 1 H, HPTI(2), J = 6.6 Hz);
* thph is the thiophene.
* Bz is the benzoic acid moiety.
** PTI is the pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinoline.

Benzothieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
527
7.79 (m, 2 H, HPTI(1), HPTI(3)); 8.33 (d, 1 H, HPTI(4),
J = 8.8 Hz); 8.43 (s, 1 H, HPTI(7)); 12.44 (br.s, 1 H, NH).
13C NMR (DMSOꢀd6), δ: 22.15 (C(9)H2); 22.35 (C(10)H2);
28.41 (C(8)H2); 32.31 (C(11)H2); 112.13, 122.39, 123.39, 125.08,
127.24, 128.11, 128.98, 129.62, 130.04, 132.95, 133.30, 156.10,
157.16, 161.44 (C=O).
S, 9.88. C17H16N2O3S. Calculated (%): C, 62.18; H, 4.91; N, 8.53;
S, 9.76. IR, ν/cm–1: 3068, 2952, 2224 (CN); 1700 (C=O); 1592,
1436, 1272, 1084, 1044 (S=O); 772, 712. 1H NMR (DMSOꢀd6),
δ: 2.42 (s, 3 H, 4ꢀMe); 2.54 (s, 3 H, 6ꢀMe); 3.78 (s, 3 H, OMe);
4.79 (d, 1 H, CH2SO, J = 11.9 Hz); 4.88 (d, 1 H, CH2SO,
J = 11.9 Hz); 7.11 (d, 1 H, HBz(3), J = 7.3 Hz); 7.47 (m, 2 H,
HBz(4, 5)); 7.53 (s, 1 H, HPy(5)); 7.86 (d, 1 H, HBz(6), J = 7.3 Hz).
13C NMR (DMSOꢀd6), δ: 19.51 (4ꢀMe); 23.98 (6ꢀMe); 52.15
(OMe); 57.74 (CH2S(O)); 106.12 (CCN); 112.53 (CN); 126.14,
128.61, 129.94, 130.13, 130.59, 132.20, 133.26, 153.61, 162.08,
163.67, 166.65 (C=O).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfinyl}ꢀ5,6,7,8ꢀ
tetrahydroquinoline (5b). The yield was 76%, m.p. 168—170 °C
(acetone—hexane). Found (%): C, 64.50; H, 5.04; N, 8.02;
S, 9.18. C19H18N2O3S. Calculated (%): C, 64.39; H, 5.12; N, 7.90;
S, 9.05. IR, ν/cm–1: 3068, 2940, 2228 (CN); 1716 (C=O); 1432,
1268, 1068 (S=O); 760, 712. 1H NMR (DMSOꢀd6), δ: 1.76
(m, 2 H, C(6)H2); 1.84 (m, 2 H, C(7)H2); 2.81 (t, 2 H, C(5)H2,
J = 5.9 Hz); 2.86 (t, 2 H, C(8)H2, J = 5.9 Hz); 3.76 (s, 3 H, OMe);
4.79 (d, 1 H, CH2SO, J = 12.4 Hz); 4.90 (d, 1 H, CH2SO,
J = 12.4 Hz); 7.16 (d, 1 H, HBz(3), J = 6.6 Hz); 7.48 (t, 2 H, HBz(4),
HBz(5), J = 8.1 Hz); 7.85 (d, 1 H, HBz(6), J = 7.3 Hz); 8.09
(s, 1 H, Hꢀ(4) of tetrahydroquinoline). 13C NMR (DMSOꢀd6),
δ: 21.30 (C(6)H2); 21.71 (C(7)H2); 27.52 (C(5)H2); 32.28
(C(8)H2); 52.16 (OMe); 57.72 (CH2S(O)); 105.06 (CCN); 113.81
(CN); 128.60, 129.93, 130.17, 130.59, 132.27, 133.33, 135.28,
143.06, 160.34, 162.17, 166.67 (C=O).
7,9ꢀDiphenylpyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀ
one (4c). The yield was 74%, m.p. 279—280 °C (DMF—MeOH).
Found (%): C, 77.48; H, 3.84; N, 6.77; S, 7.81. C26H16N2OS.
Calculated (%): C, 77.21; H, 3.99; N, 6.93; S, 7.93. IR, ν/cm–1
:
3378 (NH); 3051, 3036, 1664 (C=O); 1608, 1544, 1464, 1328,
1
1144, 872, 764, 756. H NMR (DMSOꢀd6), δ: 7.53 (m, 3 H,
H9ꢀPh(3), H9ꢀPh(4), H9ꢀPh(5)); 7.62 (t, 1 H, HPTI(2), J = 6.6 Hz);
7.70—7.80 (m, 5 H, 7ꢀPh); 7.88 (m, 2 H, HPTI(1), HPTI(3));
7.99 (s, 1 H, HPTI(8)); 8.26 (m, 3 H, HPTI(4), H9ꢀPh(2), H9ꢀPh(6));
12.55 (br.s, 1 H, NH).
9ꢀ(4ꢀBromophenyl)ꢀ7ꢀphenylpyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone (4d). The yield was 72%, m.p. 323—325 °C
(decomp.) (DMF). Found (%): C, 64.43; H, 3.19; N, 5.93;
Br, 16.31; S, 6.54. C26H15BrN2OS. Calculated (%): C, 64.60;
H, 3.13; N, 5.80; Br, 16.53; S, 6.63. IR, ν/cm–1: 3368 (NH); 1668
(C=O); 1608, 1540, 1460, 1144, 1332, 1316, 1072, 1008, 832,
764, 700. 1H NMR (DMSOꢀd6), δ: 7.63 (m, 1 H, HPTI(2));
7.69—7.80 (m, 5 H, H7ꢀPh(3), H7ꢀPh(4), H7ꢀPh(5) and H9ꢀPh(2),
H9ꢀPh(6)); 7.89 (m, 2 H, HPTI(1), HPTI(3)); 7.99 (s, 1 H,
HPTI(8)); 8.19—8.31 (m, 5 H, HPTI(4), H7ꢀPh(2), H7ꢀPh(6) and
H9ꢀPh(3), H9ꢀPh(5)); 12.62 (br.s, 1 H, NH).
7ꢀPhenylꢀ9ꢀ(2ꢀthienyl)pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoꢀ
quinolinꢀ5(6H)ꢀone (4e). The yield was 76%, m.p. 302—304 °C
(DMF—MeOH). Found (%): C, 70.42; H, 3.56; N, 6.73;
S, 15.53. C24H14N2OS2. Calculated (%): C, 70.22; H, 3.44;
N, 6.82; S, 15.62. IR, ν/cm–1: 3368 (NH); 3092, 1660 (C=O);
1608, 1564, 1540, 1436, 1332, 1144, 764, 700. 1H NMR
(DMSOꢀd6), δ: 7.19 (t, 1 H, Hthph(4), J = 5.1 Hz); 7.59 (m, 1 H,
HPTI(2)); 7.74 (m, 5 H, 7ꢀPh); 7.85 (m, 2 H, HPTI(1), HPTI(3));
7.94 (s, 1 H, HPTI(8)); 8.02 (m, 1 H, Hthph(3)); 8.22 (m, 2 H,
HPTI(4), Hthph(5)); 12.58 (br.s, 1 H, NH).
3ꢀCyanoꢀ4,6ꢀdiphenylꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfꢀ
inyl}pyridine (5c). The yield was 64%, m.p. 173—175 °C (aceꢀ
tone—diethyl ether). Found (%): C, 71.81; H, 4.37; N, 6.12;
S, 7.01. C27H20N2O3S. Calculated (%): C, 71.66; H, 4.45;
N, 6.19; S, 7.08. IR, ν/cm–1: 3032, 2956, 2228 (CN); 1708 C=O);
1576, 1512, 1368, 1272, 1064 (S=O); 1056, 776, 752, 708.
1H NMR (DMSOꢀd6), δ: 3.66 (s, 3 H, OMe); 4.98 (d, 1 H, CH2SO,
J = 12.4 Hz); 5.06 (d, 1 H, CH2SO, J = 11.7 Hz); 7.22 (d, 1 H,
HBz(3), J = 6.6 Hz); 7.49 (m, 2 H, HBz(4), HBz(5)); 7.59—7.74
(m, 8 H, 7ꢀPh and H6ꢀPh(3), H6ꢀPh(4), H6ꢀPh(5))); 7.86 (d, 1 H,
HBz(6), J = 7.3 Hz); 8.24 (m, 2 H, H6ꢀPh(2), H6ꢀPh(6)); 8.29 (s, 1 H,
HPy(5)). 13C NMR (DMSOꢀd6), δ: 52.11 (OMe); 57.78 (CH2S(O));
105.07 (CCN); 113.20 (CN); 121.90, 127.88, 128.66, 128.86,
128.88, 129.01, 129.86, 130.10, 130.28, 130.71, 131.30, 132.33,
133.43, 135.07, 135.78, 154.98, 158.68, 165.14, 166.60 (C=O).
6ꢀ(4ꢀBromophenyl)ꢀ3ꢀcyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzꢀ
yl]sulfinyl}ꢀ4ꢀphenylpyridine (5d). The yield was 74%, m.p.
165—167 °C (acetone—hexane). Found (%): C, 61.29; H, 3.51;
N, 5.42; Br, 15.29; S, 6.14. C27H19BrN2O3S. Calculated (%):
C, 61.02; H, 3.60; N, 5.27; Br, 15.04; S, 6.03. IR, ν/cm–1: 3064,
3004, 2948, 2220 (CN); 1716 (C=O); 1576, 1516, 1468, 1432,
1256, 1076 (S=O); 1008, 768, 700. 1H NMR (DMSOꢀd6), δ: 3.66
(s, 3 H, OMe); 4.97 (d, 1 H, CH2SO, J = 12.4 Hz); 5.05 (d, 1 H,
CH2SO, J = 12.4 Hz); 7.22 (d, 1 H, HBz(3), J = 6.6 Hz); 7.49
(m, 2 H, HBz(4), HBz(5)); 7.57—7.70 (m, 5 H, 7ꢀPh); 7.77 (d, 2 H,
H6ꢀPh(2), H6ꢀPh(6), J = 8.1 Hz); 7.85 (d, 1 H, HBz(6), J = 6.6 Hz);
8.19 (d, 2 H, H6ꢀPh(3), H6ꢀPh(5), J = 8.1 Hz); 8.33 (s, 1 H,
HPy(5)). 13C NMR (DMSOꢀd6), δ: 52.14 (OMe); 57.79 (CH2S(O));
105.33 (CCN); 113.14 (CN); 121.94, 125.28, 128.70, 128.88,
128.91, 129.85, 129.89, 130.03, 130.35, 130.71, 132.02, 132.35,
133.48, 134.97, 135.00, 155.12, 157.51, 165.23, 166.60 (C=O).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfinyl}ꢀ4ꢀphenylꢀ
6ꢀ(2ꢀthienyl)pyridine (5e). The yield was 65%, m.p. 173—176 °C
(acetone—diethyl ether). Found (%): C, 65.60; H, 3.85; N, 5.98;
S, 14.09. C25H18N2O3S2. Calculated (%): C, 65.48; H, 3.96;
9ꢀPhenylꢀ7ꢀ(trifluoromethyl)pyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone (4f). The yield was 84%, m.p. 267—268 °C
(DMF—MeOH). Found (%): C, 63.79; H, 2.71; N, 6.98; S, 8.14.
C21H11F3N2OS. Calculated (%): C, 63.63; H, 2.80; N, 7.07;
S, 8.09. IR, ν/cm–1: 3456, 3344 (NH); 3060, 1664 (C=O); 1608,
1
1464, 1416, 1372, 1300, 1236, 1168, 1136, 764, 704. H NMR
(DMSOꢀd6), δ: 7.55 (m, 3 H, H9ꢀPh(3), H9ꢀPh(4), H9ꢀPh(5));
7.71 (t, 1 H, HPTI(2), J = 7.3 Hz); 7.91 (t, 1 H, HPTI(3), J = 7.3 Hz);
7.98 (d, 1 H, HPTI(1), J = 7.3 Hz); 8.26 (m, 2 H, HH9ꢀPh(2),
H9ꢀPh(6)); 8.34 (m, 2 H, HPTI(4), HPTI(8)); 12.76 (br.s, 1 H, NH).
Synthesis of substituted 3ꢀcyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)ꢀ
benzyl]sulfinyl}pyridines 5a—f (general procedure). A 30% aqueꢀ
ous H2O2 (0.6 mL, 6 mmol) was added to a stirred suspension of
compound 3a—f (5 mmol) in AcOH (10 mL). The reaction mixꢀ
ture was stirred at 60—65 °C for 2—3 h (TLC monitoring) and
then cooled to room temperature. Acetic acid was neutralized
with aqueous Na2CO3. The target product was isolated by exꢀ
traction with CHCl3 (3×20 mL). The combined extract was dried
with MgSO4 and filtered, the solvent was evaporated in vacuo, and
the residue was subjected to chromatography on silica gel. Eluent
hexane—CHCl3 = 1 : 2, CHCl3. After concentration of the eluate,
the compound was crystallized from an appropriate solvent.
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfinyl}ꢀ4,6ꢀdiꢀ
methylpyridine (5a). The yield was 82%, m.p. 114—115 °C (aceꢀ
tone—diethyl ether). Found (%): C, 62.11; H, 5.02; N, 8.45;

528
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
Kalugin and Shestopalov
N, 6.11; S, 13.98. IR, ν/cm–1: 3120, 3056, 2948, 2228 (CN);
1712 (C=O); 1584, 1572, 1496, 1436, 1288, 1272, 1072 (S=O);
1036, 772, 724, 700. 1H NMR (DMSOꢀd6), δ: 3.70 (s, 3 H,
OMe); 4.93 (d, 1 H, CH2SO, J = 12.4 Hz); 5.01 (d, 1 H, CH2SO,
J = 12.4 Hz); 7.22 (d, 1 H, HBz(3), J = 7.3 Hz); 7.27 (t, 1 H,
Hthph(4), J = 4.4 Hz); 7.48 (m, 2 H, HBz(4), HBz(5)); 7.60 (m, 5 H,
7ꢀPh); 7.87 (d, 1 H, HBz(6), J = 7.3 Hz); 7.91 (d, 1 H, Hthph(3),
J = 5.1 Hz); 8.20 (d, 1 H, Hthph(5), J = 3.7 Hz); 8.34 (s, 1 H,
HPy(5)). 13C NMR (DMSOꢀd6), δ: 52.13 (OMe); 57.75 (CH2S(O));
104.29 (CCN); 113.17 (CN); 120.23, 128.72, 128.85, 128.92,
129.19, 129.95, 129.99, 130.25, 130.72, 130.83, 132.34, 132.61,
133.34, 134.97, 141.58, 154.38, 154.59, 165.16, 166.60 (C=O).
3ꢀCyanoꢀ6ꢀphenylꢀ4ꢀ(trifluoromethyl)ꢀ2ꢀ{[2ꢀ(methoxycarbꢀ
onyl)benzyl]sulfinyl}pyridine (5f). The yield was 66%, m.p.
126—128 °C (acetone—diethyl ether). Found (%): C, 59.87;
H, 3.28; N, 6.22; S, 7.39. C22H15F3N2O3S. Calculated (%):
C, 59.46; H, 3.40; N, 6.30; S, 7.21. IR, ν/cm–1: 3080, 2232 (CN);
1708 (C=O); 1584, 1428, 1376, 1268, 1188, 1148, 1080 (S=O);
760, 720. 1H NMR (DMSOꢀd6), δ: 3.85 (s, 3 H, OMe); 5.01 (s, 2 H,
CH2S(O)); 7.21 (d, 1 H, HBz(3), J = 6.6 Hz); 7.48 (m, 2 H,
HBz(4), HBz(5)); 7.61 (m, 3 H, H6ꢀPh(3), H6ꢀPh(4), H6ꢀPh(5));
7.84 (d, 1 H, HBz(6), J = 7.3 Hz); 8.24 (d, 2 H, H6ꢀPh(2), H6ꢀPh(6),
J = 7.3 Hz); 8.61 (s, 1 H, HPy(5)). 13C NMR (DMSOꢀd6), δ: 52.03
(OMe); 57.88 (CH2S(O)); 102.42 (CCN); 110.30 (CN); 118.31
(q, J = 4.4 Hz); 121.06 (q, CF3, J = 276.2 Hz); 128.19, 128.72,
129.15, 129.73, 129.78, 130.69, 132.22, 132.35, 133.45, 134.72,
141.43 (q, CCF3, J = 33.2 Hz); 160.12, 165.54, 166.94 (C=O).
Synthesis of substituted 3ꢀcyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)ꢀ
benzyl]sulfonyl}pyridines 7a—f (general procedure). Powdered
KMnO4 (1.26 g, 8 mmol) was added to a stirred solution or
suspension of compound 3a—f ((5 mmol) in AcOH (20—25 mL)
at such a rate that to keep the reaction temperature within
20—25 °C. The reaction mixture was stirred for additional 40 min,
then discolored by the addition of aqueous Na2SO3, and poured into
H2O (100 mL). The product was collected by filtration, washed
with H2O, dried, and crystallized from an appropriate solvent.
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfonyl}ꢀ4,6ꢀdimeꢀ
thylpyridine (7a). The yield was 77%, m.p. 127—129 °C (MeOH).
Found (%): C, 59.19; H, 4.82; N, 8.03; S, 9.41. C17H16N2O4S.
line). 13C NMR (DMSOꢀd6), δ: 21.02 (C(6)H2); 21.52 (C(7)H2);
27.57 (C(5)H2); 32.01 (C(8)H2); 52.17 (OMe); 55.17 (CH2SO2);
104.29 (CCN); 113.81 (CN); 127.77, 129.08, 130.54, 131.02,
132.19, 133.92, 137.72, 144.03, 153.49, 161.93, 166.84 (C=O).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfonyl}ꢀ4,6ꢀdiꢀ
phenylpyridine (7c). The yield was 84%, m.p. 175—177 °C
(CHCl3—MeOH). Found (%): C, 69,39; H, 4.35; N, 6.05; S, 6.95.
C27H20N2O4S. Calculated (%): C, 69.22; H, 4.30; N, 5.98;
S, 6.84. IR, ν/cm–1: 3016, 2952, 2228 (CN); 1712 (C=O); 1584,
1572, 1492, 1428, 1328 (SO2); 1276, 1144, 1120 (SO2); 1080,
776, 752, 700. 1H NMR (DMSOꢀd6), δ: 3.72 (s, 3 H, OMe); 5.66
(s, 2 H, CH2SO2); 7.44 (t, 1 H, HBz(4), J = 7.3 Hz); 7.49—7.68
(m, 8 H, HBz(3), HBz(5), H6ꢀPh(3), H6ꢀPh(4), H6ꢀPh(5), H4ꢀPh(3),
H4ꢀPh(4), H4ꢀPh(5)); 7.73 (m, 2 H, H4ꢀPh(2), H4ꢀPh(6)); 7.88
(d, 1 H, HBz(6), J = 7.3 Hz); 8.29 (m, 2 H, H6ꢀPh(2), H6ꢀPh(6)); 8.49
(s, 1 H, HPy(5)). 13C NMR (DMSOꢀd6), δ: 52.13 (OMe); 55.02
(CH2SO2); 103.71 (CCN); 113.07 (CN); 123.66, 127.57, 127.96,
128.75, 129.06, 129.12, 129.20, 130.31, 130.60, 131.16, 131.57, 132.26,
134.09, 135.06, 135.13, 156.79, 157.91, 158.46, 166.86 (C=O).
6ꢀ(4ꢀBromophenyl)ꢀ3ꢀcyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzꢀ
yl]sulfonyl}ꢀ4ꢀphenylpyridine (7d). The yield was 83%, m.p.
191—193 °C (MeOH). Found (%): C, 59.33; H, 3.44; N, 5.19;
Br, 14.82; S, 5.95. C27H19BrN2O4S. Calculated (%): C, 59.24;
H, 3.50; N, 5.12; Br, 14.60; S, 5.86. IR, ν/cm–1: 3052, 3016,
2956, 2912, 2232 (CN); 1708 (C=O); 1580, 1508, 1488, 1432,
1332 (SO2); 1296, 1272, 1136 (SO2); 1120, 1072, 1008, 840, 772,
1
760, 700. H NMR (DMSOꢀd6), δ: 3.72 (s, 3 H, OMe); 5.63
(s, 2 H, CH2SO2); 7.47—7.68 (m, 6 H, HBz(3), HBz(4), HBz(5),
H4ꢀPh(3), H4ꢀPh(4), H4ꢀPh(5)); 7.72 (m, 2 H, H4ꢀPh(2), H4ꢀPh(6));
7.79 (d, 2 H, H6ꢀPh(2), H6ꢀPh(6), J = 8.1 Hz); 7.89 (d, 1 H,
HBz(6), J = 7.3 Hz); 8.23 (d, 2 H, H6ꢀPh(3), H6ꢀPh(5), J = 8.1 Hz);
8.50 (s, 1 H, HPy(5)). 13C NMR (DMSOꢀd6), δ: 52.13 (OMe);
55.08 (CH2SO2); 104.06 (CCN); 113.00 (CN); 123.75, 125.55,
127.53, 128.72, 129.03, 129.19, 129.85, 130.32, 130.57, 131.04,
132.06, 132.25, 134.05, 134.29, 134.92, 156.73, 156.89, 158.33,
166.80 (C=O).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfonyl}ꢀ4ꢀphenylꢀ
6ꢀ(2ꢀthienyl)pyridine (7e). The yield was 71%, m.p. 179—180 °C
(CHCl3—MeOH). Found (%): C, 63.44; H, 3.98; N, 5.81;
S, 13.73. C25H18N2O4S2. Calculated (%): C, 63.28; H, 3.82;
N, 5.90; S, 13.51. IR, ν/cm–1: 3016, 2991, 2949, 2923, 2224 (CN);
1709 (C=O); 1578, 1556, 1506, 1438, 1329 (SO2), 1295, 1260,
1143, 1120 (SO2); 1079, 895, 978, 778, 725, 701. 1H NMR
(DMSOꢀd6), δ: 3.77 (s, 3 H, OMe); 5.64 (s, 2 H, CH2SO2); 7.32
(t, 1 H, Hthph(4), J = 4.4 Hz); 7.53—7.67 (m, 6 H, HBz(3),
HBz(4), HBz(5), H4ꢀPh(3), H4ꢀPh(4), H4ꢀPh(5)); 7.70 (m, 2 H,
H4ꢀPh(2), H4ꢀPh(6)); 7.93 (d, 1 H, HBz(6), J = 7.3 Hz); 7.99 (d, 1 H,
Hthph(3), J = 4.4 Hz); 8.30 (d, 1 H, Hthph(5), J = 2.9 Hz); 8.45
(s, 1 H, HPy(5)). 13C NMR (DMSOꢀd6), δ: 52.24 (OMe); 54.63
(CH2SO2); 102.62 (CCN); 113.11 (CN); 122.00, 127.40, 128.81,
128.98, 129.31, 129.47, 130.34, 130.63, 130.71, 131.34, 132.33,
133.15, 134.11, 134.98, 140.89, 153.60, 156.52, 158.59, 166.93 (C=O).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfonyl}ꢀ6ꢀphenylꢀ
4ꢀ(trifluoromethyl)pyridine (7f). The yield was 80%, m.p.
158—160 °C (CHCl3—MeOH). Found (%): C, 57.21; H, 3.39;
N, 6.22; S, 6.89. C22H15F3N2O4S. Calculated (%): C, 57.39;
H, 3.28; N, 6.08; S, 6.96. IR, ν/cm–1: 3092, 2988, 2928, 2236 (CN);
1716 (C=O); 1596, 1432, 1384, 1340 (SO2); 1268, 1148 (SO2);
Calculated (%): C, 59.29; H, 4.68; N, 8.13; S, 9.31. IR, ν/cm–1
:
3036, 3008, 2948, 2232 (CN), 1712 (C=O); 1596, 1448, 1428,
1320 (SO2), 1268, 1160, 1120 (SO2); 1080, 884, 780, 700.
1H NMR (DMSOꢀd6), δ: 2.52 (s, 3 H, 4ꢀMe); 2.81 (s, 3 H, 6ꢀMe);
3.78 (s, 3 H, OMe); 5.46 (s, 2 H, CH2SO2); 7.47 (t, 1 H, HBz(4),
J = 7.3 Hz); 7.53 (d, 1 H, HBz(3), J = 7.3 Hz); 7.59 (t, 1 H,
HBz(5), J = 7.3 Hz); 7.74 (s, 1 H, HPy(5)); 7.87 (d, 1 H, HBz(6),
J = 7.3 Hz). 13C NMR (DMSOꢀd6), δ: 20.05 (4ꢀMe); 23.86
(6ꢀMe); 52.20 (OMe); 54.72 (CH2SO2); 104.96 (CCN); 112.52
(CN); 127.63, 128.04, 129.12, 130.55, 131.24, 132.15, 133.94,
155.03, 156.94, 161.65, 166.93 (C=O).
3ꢀCyanoꢀ2ꢀ{[2ꢀ(methoxycarbonyl)benzyl]sulfonyl}ꢀ5,6,7,8ꢀ
tetrahydroquinoline (7b). The yield was 78%, m.p. 153—155 °C
(CHCl3—MeOH). Found (%): C, 61.48; H, 5.01; N, 7.52;
S, 8.51. C19H18N2O4S. Calculated (%): C, 61.61; H, 4.90;
N, 7.56; S, 8.65. IR, ν/cm–1: 3052, 3008, 2956, 2936, 2232 (CN);
1716 (C=O); 1596, 1580, 1432, 1320 (SO2); 1296, 1276, 1132
1
(SO2); 1080, 780, 708. H NMR (DMSOꢀd6), δ: 1.78 (m, 2 H,
C(6)H2); 1.87 (m, 2 H, C(7)H2); 2.86 (t, 2 H, C(5)H2, J = 5.9 Hz);
2.90 (t, 2 H, C(8)H2, J = 5.9 Hz); 3.76 (s, 3 H, OMe); 5.41
(s, 2 H, CH2SO2); 7.46 (t, 1 H, HBz(4), J = 7.3 Hz); 7.53 (d, 1 H,
HBz(3), J = 7.3 Hz); 7.58 (t, 1 H, HBz(5), J = 7.3 Hz); 7.86 (d, 1
H, HBz(6), J = 7.3 Hz); 8.26 (s, 1 H, H(4) of tetrahydroquinoꢀ
1
1080, 780, 692. H NMR (DMSOꢀd6), δ: 3.71 (s, 3 H, OMe);
5.62 (s, 2 H, CH2SO2); 7.55 (t, 1 H, HBz(4), J = 6.6 Hz); 7.59—7.68
(m, 5 H, HBz(3), HBz(5), H6ꢀPh(3), H6ꢀPh(4), H6ꢀPh(5)); 7.88
(d, 1 H, HBz(6), J = 7.3 Hz); 8.30 (d, 2 H, H6ꢀPh(2), H6ꢀPh(6),

Benzothieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
529
J = 6.6 Hz); 8.82 (s, 1 H, HPy(5)). 13C NMR (DMSOꢀd6), δ: 52.16
(OMe); 55.50 (CH2SO2); 101.78 (CCN); 110.56 (CN); 120.35
(q, CF3, J = 276.2 Hz); 120.57, 127.32, 128.36, 129.29, 129.35,
130.68, 130.98, 132.40, 132.57, 134.12, 134.25, 142.75 (q, CCF3,
J = 33.2 Hz); 159.04, 160.04, 166.81 (C=O).
315—318 °C (decomp.) (CHCl3—hexane). Found (%): C, 62.85;
H. 2.88; N, 5.76; Br, 15.77; S, 6.33. C26H15BrN2O2S. Calculatꢀ
ed (%): C, 62.53; H, 3.03; N, 5.61; Br, 16.00; S, 6.42. IR, ν/cm–1
:
3365 (NH); 3030, 2950, 2807, 1660 (C=O); 1612, 1492, 1228,
1
1072 (S=O); 1056, 1008, 764, 696. H NMR (DMSOꢀd6), δ:
Synthesis of substituted pyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone 11ꢀoxides 6a—f (general procedure). Poꢀ
tassium tertꢀbutoxide (0.51 g, 4.5 mmol) was added to a solution
of compound 5a—f (3 mmol in anhydrous DMF (5 mL). The
reaction mixture was stirred at 55—60 °C for 1 h and then poured
into H2O (40 mL), followed by the addition of AcOH (0.4 mL)
to the obtained mixture. The crystals formed were collected by
filtration and dried. Compounds 6a and 6b were crystallized
from a mixture of DMF—MeOH, while compounds 6c—f were
purified by chromatography on silica gel. Eluent
CHCl3—hexane (2 : 1, 3 : 1) and CHCl3. After concentration of the
eluate, the compounds were crystallized from an appropriate solvent.
7,9ꢀDimethylpyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀ
one 11ꢀoxide (6a). The yield was 52%, m.p. > 330 °C (decomp.)
(DMF—MeOH). Found (%): C, 64.68; H, 4.17; N, 9.55;
S, 10.71. C16H12N2O2S. Calculated (%): C, 64.85; H, 4.08;
N, 9.45; S, 10.82. IR, ν/cm–1: 3227 (NH); 1676 (C=O); 1608, 1572,
1552, 1436, 1324, 1136, 1040 (S=O); 756. 1H NMR (DMSOꢀd6),
δ: 2.56 (s, 3 H, 7ꢀMe); 2.89 (s, 3 H, 9ꢀMe); 7.30 (s, 1 H, HPTI(8));
7.58 (t, 1 H, HPTI(2), J = 8.1 Hz); 7.81 (t, 1 H, HPTI(3), J = 7.3 Hz);
8.05 (d, 1 H, HPTI(1), J = 8.1 Hz); 8.34 (d, 1 H, HPTI(4),
J = 8.8 Hz); 11.85 (br.s, 1 H, NH). 13C NMR (DMSOꢀd6), δ:
19.18 (7ꢀMe); 23.38 (9ꢀMe); 115.61, 118.90, 122.27, 125.35,
126.38, 126.51, 128.01, 129.58, 132.95, 133.72, 145.73, 150.96,
158.32, 160.57 (C=O).
8,9,10,11ꢀTetrahydroisoquinolino[3′,4′:4,5]thieno[2,3ꢀb]ꢀ
quinolinꢀ5(6H)ꢀone 11ꢀoxide (6b). The yield was 65%, m.p.
> 330 °C (decomp.) (DMF—MeOH). Found (%): C, 67.25;
H, 4.44; N, 8.51; S, 10.07. C18H14N2O2S. Calculated (%): C, 67.06;
H, 4.38; N, 8.69; S, 9.94. IR, ν/cm–1: 3442, 3310 (NH); 3043,
2937, 1650 (C=O); 1608, 1560, 1436, 1400, 1335, 1140, 1058
(S=O); 1036, 772. 1H NMR (DMSOꢀd6), δ: 1.85 (m, 4 H,
C(9)H2, C(10)H2); 2.90 (t, 2 H, C(8)H2, J = 5.9 Hz); 2.97
(t, 2 H, C(11)H2, J = 5.9 Hz); 7.61 (t, 1 H, HPTI(2), J = 7.3 Hz);
7.82 (m, 2 H, HPTI(1), HPTI(3)); 8.34 (d, 1 H, HPTI(4), J = 8.1 Hz);
8.46 (s, 1 H, HPTI(7)); 12.28 (br.s, 1 H, NH). 13C NMR
(DMSOꢀd6), δ: 22.20 (C(9)H2); 22.40 (C(10)H2); 28.47 (C(8)H2);
32.37 (C(11)H2); 112.19, 122.48, 123.36, 125.14, 127.35, 128.18,
129.09, 129.72, 130.12, 133.01, 133.41, 156.14, 157.27, 161.55 (C=O).
7,9ꢀDiphenylpyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀ
one 11ꢀoxide (6c). The yield was 28%, m.p. 281—284 °C (aceꢀ
tone—hexane). Found (%): C, 74.45; H, 3.91; N, 6.83; S, 7.79.
C26H16N2O2S. Calculated (%): C, 74.27; H, 3.84; N, 6.66;
S, 7.62. IR, ν/cm–1: 3370 (NH); 3060, 1678 (C=O); 1609, 1551,
1426, 1324, 1069 (S=O); 1050, 759, 699. 1H NMR (DMSOꢀd6),
δ: 7.53—7.61 (m, 3 H, H9ꢀPh(3), H9ꢀPh(4), H9ꢀPh(5)); 7.65 (t, 1 H,
HPTI(2), J = 8.1 Hz); 7.70—7.82 (m, 3 H, H7ꢀPh(3), H7ꢀPh(4),
H7ꢀPh(5)); 7.92 (d, 2 H, H7ꢀPh(2), H7ꢀPh(6), J = 7.3 Hz); 7.95
(t, 1 H, HPTI(3), J = 7.3 Hz); 8.02 (d, 1 H, HPTI(1), J = 8.1 Hz);
8.12 (s, 1 H, HPTI(8)); 8.20 (d, 1 H, HPTI(4), J = 8.1 Hz); 8.26
(m, 2 H, H9ꢀPh(2), H9ꢀPh(6)); 12.60 (br.s, 1 H, NH). 13C NMR
(DMSOꢀd6), δ: 106.17, 116.41, 118.08, 122.26, 124.26, 127.72,
128.19, 128.74, 128.86, 129.22, 129.57, 130.35, 130.92, 131.12, 132.31,
133.24, 135.99, 136.02, 144.77, 151.39, 159.74, 161.98 (C=O).
9ꢀ(4ꢀBromophenyl)ꢀ7ꢀphenylpyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone 11ꢀoxide (6d). The yield was 22%, m.p.
7.56 (m, 3 H, H7ꢀPh(3), H7ꢀPh(4), H7ꢀPh(5)); 7.69—7.83 (m, 5 H,
HPTI(2), H7ꢀPh(2), H7ꢀPh(6) and H9ꢀPh(2), H9ꢀPh(6)); 7.87—7.94
(m, 2 H, HPTI(1), HPTI(3)); 8.20—8.33 (m, 4 H, HPTI(4),
HPTI(8), H9ꢀPh(3), H9ꢀPh(5)); 12.85 (br.s, 1 H, NH). 13C NMR
(DMSOꢀd6), δ: 106.66, 116.50, 118.52, 123.84, 124.79, 127.60,
128.26, 128.78, 129.18, 129.49, 129.79, 130.36, 131.78, 132.03,
133.18, 133.95, 136.04, 136.06, 145.62, 150.90, 159.45, 162.47
(C=O).
7ꢀPhenylꢀ9ꢀ(2ꢀthienyl)pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoꢀ
quinolinꢀ5(6H)ꢀone 11ꢀoxide (6e). The yield was 25%, m.p.
> 320 °C (decomp.) (acetone—hexane). Found (%): C, 67.37;
H, 3.23; N, 6.64; S, 15.11. C24H14N2O2S2. Calculated (%):
C, 67.59; H, 3.31; N, 6.57; S, 15.03. IR, ν/cm–1: 3369 (NH); 3030,
1660 (C=O); 1611, 1491, 1353, 1073 (S=O); 1008, 763, 695.
1H NMR (DMSOꢀd6), δ: 7.25 (t, 1 H, Hthph(4), J = 4.4 Hz);
7.58 (m, 3 H, H7ꢀPh(3), H7ꢀPh(4), H7ꢀPh(5)); 7.68—7.76 (m, 3 H,
HPTI(2), H7ꢀPh(2), H7ꢀPh(6)); 7.87 (m, 2 H, HPTI(3), Hthph(3));
8.01—8.08 (m, 2 H, HPTI(1), HPTI(8)); 8.23 (m, 2 H, HPTI(4),
Hthph(5)); 12.65 (br.s, 1 H, NH). 13C NMR (DMSOꢀd6), δ:
106.60, 116.37, 117.19, 123.89, 127.60, 128.29, 128.78, 128.94,
129.09, 129.64, 129.95, 130.09, 130.38, 131.06, 132.72, 134.07,
136.01, 143.28, 145.52, 150.62, 158.44, 162.57(C=O).
9ꢀPhenylꢀ7ꢀ(trifluoromethyl)pyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone 11ꢀoxide (6f). The yield was 21%, m.p.
263—266 °C (acetone—hexane). Found (%): C, 61.11; H, 2.75;
N, 6.63; S, 7.67. C21H11F3N2O2S. Calculated (%): C, 61.16;
H, 2.69; N, 6.79; S, 7.77. IR, ν/cm–1: 3454, 3339, 3290 (NH);
3065, 3038, 1669 (C=O); 1607, 1463, 1372, 1298, 1266, 1237,
1
1169, 1140, 1079 (S=O); 764, 686. H NMR (DMSOꢀd6), δ:
7.52—7.64 (m, 3 H, H9ꢀPh(3), H9ꢀPh(4), H9ꢀPh(5)); 7.74 (t, 1 H,
HPTI(2), J = 8.1 Hz); 7.94 (t, 1 H, HPTI(3), J = 7.3 Hz); 8.01
(d, 1 H, HPTI(1), J = 7.3 Hz); 8.29 (m, 2 H, H9ꢀPh(2), H9ꢀPh(6));
8.38 (d, 1 H, HPTI(4), J = 7.3 Hz); 8.40 (s, 1 H, HPTI(8)); 11.80
(br.s, 1 H, NH). 13C NMR (DMSOꢀd6), δ: 94.61, 102.75. 113.47,
120.77, 121.40 (q, CF3, J = 274.5 Hz); 123.36, 125.97, 127.43,
127.97, 129.00, 129.51, 131.73, 132.66, 132.85, 135.16, 144.91
(q, CCF3, J = 34.5 Hz); 150.08, 156.30, 162.54 (C=O).
Synthesis of substituted pyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone 11,11ꢀdioxides 8a—e was carried out acꢀ
cording to the procedure described for heterocycles 4a—f.
7,9ꢀDimethylpyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀ
one 11,11ꢀdioxide (8a). The yield was 75%, m.p. > 330 °C
(decomp.) (DMF—MeOH). Found (%): C, 61.77; H, 3.71; N, 9.06;
S, 10.41. C16H12N2O3S. Calculated (%): C, 61.53; H, 3.87;
N, 8.97; S, 10.26. IR, ν/cm–1: 3220 (NH); 2984, 1652 (C=O); 1612,
1584, 1496, 1436, 1316 (SO2); 1304, 1152 (SO2); 1112, 1080,
768. 1H NMR (DMSOꢀd6), δ: 2.59 (s, 3 H, 7ꢀMe); 2.87 (s, 3 H,
9ꢀMe); 7.49 (s, 1 H, HPTI(8)); 7.70 (t, 1 H, HPTI(2), J = 6.6 Hz);
7.94 (m, 2 H, HPTI(1), HPTI(3)); 8.34 (d, 1 H, HPTI(4), J = 8.1 Hz);
12.80 (s, 1 H, NH). 13C NMR (DMSOꢀd6), δ: 19.66 (7ꢀMe);
23.36 (9ꢀMe); 117.22, 119.15, 121.76, 126.36, 127.91, 128.43,
129.14, 129.78, 132.02, 134.36, 145.74, 156.18, 160.79, 162.82
(C=O).
8,9,10,11ꢀTetrahydroisoquinolino[3′,4′:4,5]thieno[2,3ꢀb]ꢀ
quinolinꢀ5(6H)ꢀone 13,13ꢀdioxide (8b). The yield was 75%, m.p.
> 330 °C (decomp.) (DMF—MeOH). Found (%): C, 64.02;

530
Russ.Chem.Bull., Int.Ed., Vol. 66, No. 3, March, 2017
Kalugin and Shestopalov
H, 4.09; N, 8.41; S, 9.29. C18H14N2O3S. Calculated (%): C, 63.89;
H, 4.17; N, 8.28; S, 9.47. IR, ν/cm–1: 3440 (NH); 3044, 2936,
2864, 1664, 1648 (C=O); 1620, 1584, 1548, 1480, 1432, 1372,
1336, 1308 (SO2), 1256, 1144 (SO2); 1096, 1004, 772, 684.
1H NMR (DMSOꢀd6), δ: 1.83 (m, 4 H, C(9)H2, C(10)H2); 2.74
(t, 2 H, C(8)H2, J = 5.9 Hz); 2.94 (t, 2 H, C(11)H2, J = 5.9 Hz);
7.54 (t, 1 H, HPTI(2), J = 7.3 Hz); 7.87 (m, 2 H, HPTI(1),
HPTI(3)); 8.33 (m, 2 H, HPTI(4), HPTI(7)); 12.70 (br.s, 1 H, NH).
13C NMR (DMSOꢀd6), δ: 21.48 (C(9)H2); 21.88 (C(10)H2);
28.44 (C(8)H2); 32.03 (C(11)H2); 109.02, 119.63, 121.68, 125.02,
128.02, 128.41, 129.11, 129.72, 131.40, 134.09, 137.24, 153.52,
160.24, 162.78 (C=O).
7,9ꢀDiphenylpyrido[3´,2´:4,5]thieno[3,2ꢀc]isoquinolinꢀ5(6H)ꢀ
one 11,11ꢀdioxide (8c). The yield was 82%, m.p. 314—316 °C
(DMF—MeOH). Found (%): C, 71.68; H, 3.54; N, 6.33;
S, 7.51. C26H16N2O3S. Calculated (%): C, 71.55; H, 3.69; N, 6.42;
S, 7.35. IR, ν/cm–1: 3332 (NH), 3056, 1692 (C=O); 1608, 1572,
1552, 1428, 1308 (SO2); 1156, 1136 (SO2); 1092, 764, 700.
1H NMR (DMSOꢀd6), δ: 7.57 (m, 3 H, H9ꢀPh(3), H9ꢀPh(4),
H9ꢀPh(5)); 7.71 (m, 4 H, HPTI(2), H7ꢀPh(3), H7ꢀPh(4), H7ꢀPh(5));
7.86 (m, 2 H, HPTI(1), HPTI(3)); 7.96 (m, 2 H, H7ꢀPh(2),
H7ꢀPh(6)); 8.27 (m, 4 H, HPTI(4), HPTI(8), H9ꢀPh(2), H9ꢀPh(6));
11.90 (br.s, 1 H, NH). 13C NMR (DMSOꢀd6), δ: 110.43, 116.96,
122.33, 124.70, 125.63, 127.43, 128.52, 128.71, 128.92 (d,
J = 2.2 Hz); 129.20, 129.24, 129.28, 129.54, 130.61, 130.99, 134.83,
135.08, 135.89, 147.27, 157.21, 157.98, 160.59 (C=O).
m.p. 332—334 °C (decomp.) (DMF—MeOH). Found (%):
C, 58.65; H, 2.71; N, 6.68; S, 7.34. C21H11F3N2O3S. Calculatꢀ
ed (%): C, 58.88; H, 2.59; N, 6.54; S, 7.48. IR, ν/cm–1: 3264 (NH);
3068, 1680 (C=O); 1608, 1580, 1464, 1432, 1372, 1356,
1
1316 (SO2); 1144, 1132 (SO2); 1096, 896, 764, 704. H NMR
(DMSOꢀd6), δ: 7.61 (m, 3 H, H9ꢀPh(3), H9ꢀPh(4), H9ꢀPh(5));
7.84 (t, 1 H, HPTI(2), J = 7.3 Hz); 8.08 (m, 2 H, HPTI(1),
HPTI(3)); 8.31 (m, 2 H, H9ꢀPh(2), H9ꢀPh(6)); 8.40 (d, 1 H,
HPTI(4), J = 8.8 Hz); 8.58 (s, 1 H, HPTI(8)); 11.93 (br.s, 1 H,
NH). 13C NMR (DMSOꢀd6), δ: 96.24, 101.62, 109.23, 120.76
(q, J = 5.8 Hz); 121.79 (q, CF3, J = 274.5 Hz); 121,93, 126.76
(d, J = 15.1 Hz); 127.35 (d, J = 13.4 Hz); 128.64, 129.12, 129.39,
129.53, 131.24, 133.17 (q, CCF3, J = 34.5 Hz); 134.16, 135.14,
158.65, 159.15, 164.58 (C=O).
References
1. C. Szabo, V. L. Dawson, Trends Pharmacol. Sci., 1998,
19, 287.
2. J. Prakash, R. Aloka, W. William, US Pat. 7,393,955, 2008;
Chem. Abstr., 2008, 149, 128753.
3. D. Strumberg, Y. Pommier, K. Paull, M. Jayaraman, P. Naꢀ
gafuji, M. Cushman, J. Med. Chem., 1999, 42, 446.
4. M. Cushman, M. Jayaraman, J. A. Vroman, A. K. Fukunaꢀ
ga, B. M. Fox, G. Kohlhagen, D. Strumbergt, Y. Pommier,
J. Med. Chem., 2000, 43, 3688.
5. L. F. Tietze, G. Brasche, K. M. Gericke, in Domino Reactions
in Organic Synthesis, WileyꢀVCH, Weinheim, 2006, p. 617.
6. V. E. Kalugin, A. M. Shestopalov, Tetrahedron Lett., 2011,
52, 1557.
7. V. E. Kalugin, A. M. Shestopalov, Russ. Chem. Bull., 2014,
63, 2478.
8. V. E. Kalugin, A. M. Shestopalov, Russ. Chem. Bull., 2015,
64, 878.
9. V. E. Kalugin, A. M. Shestopalov, Russ. Chem. Bull., 2014,
63, 426.
10. K. Gewald, M. Hentschel, U. Illgen, J. Pract. Chem., 1974,
316, 1030.
11. A. M. Shestopalov, L. A. Rodinovskaya, Yu. A. Sharanin,
V. P. Litvinov, J. Gen. Chem. USSR, 1988, 58, 745.
12. L. A. Rodinovskaya, Yu. A. Sharanin, V. P. Litvinov, A. M.
Shestopalov, V. K. Promonenkov, B. M. Zolotarev, V. Yu.
Mortikov, J. Org. Chem. USSR, 1985, 21, 2230.
13. V. A. Kovtunenko, A. K. Tyltin, T. T. Dobrenko, F. S.
Babichev, Ukr. Khim. Zh. [Ukr. Chem. J.] 1983, 49, 1099
(in Russain).
14. A. A. Krauze, Z. A. Bomika, A. M. Shestopalov, L. A. Rodiꢀ
novskaya, Yu. E. Pelcher, G. Ya. Dubur, Yu. A. Sharanin,
V. K. Promonenkov, Chem. Heterocycl. Compd., Engl. Transl.,
1981, 17, 279.
9ꢀ(4ꢀBromophenyl)ꢀ7ꢀphenylpyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone 11,11ꢀdioxide (8d). The yield was 86%,
m.p. 323—325 °C (DMF—MeOH). Found (%): C, 60.41;
H, 3.03; N, 5.57; Br, 15.33; S, 6.15. C26H15BrN2O3S. Calculatꢀ
ed (%): C, 60.59; H, 2.93; N, 5.44; Br, 15.50; S, 6.22. IR, ν/cm–1
:
3360, 3348 (NH); 1672 (C=O); 1616, 1576, 1556, 1440, 1308
(SO2); 1160, 1136 (SO2); 1092, 836, 764, 704. 1H NMR
(DMSOꢀd6), δ: 7.69 (m, 4 H, HPTI(2), H7ꢀPh(3), H7ꢀPh(4),
H7ꢀPh(5)); 7.77 (d, 2 H, J = 8.8 Hz, H9ꢀPh(2), H9ꢀPh(6)); 7.84
(m, 2 H, HPTI(1), HPTI(3)); 7.95 (m, 2 H, H7ꢀPh(2), H7ꢀPh(6));
8.25 (m, 4 H, HPTI(4), HPTI(8), H9ꢀPh(3), H9ꢀPh(5)); 12.42 (br.s,
1 H, NH). 13C NMR (DMSOꢀd6), δ: 110.08, 117.43, 122.10,
124.54, 124.59, 125.57, 128.33, 128.63, 128.66, 128.79, 129.11,
129.24, 129.26, 130.38, 132.03, 134.49, 134.90, 134.95, 147.24,
156.50, 157.17, 160.83 (C=O).
7ꢀPhenylꢀ9ꢀ(2ꢀthienyl)pyrido[3´,2´:4,5]thieno[3,2ꢀc]isoꢀ
quinolinꢀ5(6H)ꢀone 11,11ꢀdioxide (8e). The yield was 66%, m.p.
323—326 °C (decomp.) (DMF—MeOH). Found (%): C, 65.31;
H, 3.05; N, 6.24; S, 14.31. C24H14N2O3S2. Calculated (%):
C, 65.14; H, 3.19; N, 6.33; S, 14.19. IR, ν/cm–1: 3292, 3273 (NH);
3140, 3095, 3035, 2918, 1636 (C=O); 1601, 1521, 1476, 1419,
1325 (SO2); 1233, 1179, 1128 (SO2), 1071, 905, 825, 729, 699.
1H NMR (DMSOꢀd6), δ: 7.27 (t, 1 H, Hthph(4)), J = 4.4 Hz);
7.55—7.65 (m, 3 H, H7ꢀPh(3), H7ꢀPh(4), H7ꢀPh(5)); 7.71 (m, 3 H,
HPTI(2), H7ꢀPh(2), H7ꢀPh(6)); 7.89 (m, 2 H, HPTI(3), Hthph(3));
8.08 (m, 2 H, HPTI(1), Hthph(5)); 8.33 (s, 2 H, HPTI(4), HPTI(8));
12.68 (br.s, 1 H, NH). 13C NMR (DMSOꢀd6), δ: 106.91, 116.32,
122.04, 124.42, 125.66, 126.33, 128.20, 128.50, 128.72, 128.82,
128.96, 129.39, 129.51, 130.23, 131.41, 134.36, 135.93, 141.14,
146.22, 151.78, 158.54, 162.97 (C=O).
15. l. C. C. Vieira, M. W. Paixao, A. G. Correa, Tetrahedron
Lett., 2012, 53, 2712.
16. Yu. A. Sharanin, V. K. Promonenkov, A. M. Shestopalov,
J. Org. Chem. USSR, 1982, 18, 548.
9ꢀPhenylꢀ7ꢀ(trifluoromethyl)pyrido[3´,2´:4,5]thieno[3,2ꢀc]ꢀ
isoquinolinꢀ5(6H)ꢀone 11,11ꢀdioxide (8f). The yield was 60%,
Received July 31, 2015;
in revised form May 24, 2016