The synthesis of substituted 5-aminopyrido[3′,2′:4,5]thieno[3,2-c]isoquinolines and their sulfinyl and sulfonyl derivatives

Article abstract of DOI:10.1007/s11172-018-2155-y

5-Aminopyrido[3′,2′:4,5]thieno[3,2-c]isoquinolines were synthesized via alkylation of 3-cyanopyridine-2(1H)-thiones with 2-(chloromethyl)benzonitrile followed by treatment of the products with potassium tert-butoxide. The oxidation of the alkylated produc

Full text of DOI:10.1007/s11172-018-2155-y

Russian Chemical Bulletin, International Edition, Vol. 67, No. 5, pp. 902—911, May, 2018
902
The synthesis of substituted 5-aminopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines
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 (499) 952 5308. E-mail: vek@ioc.ac.ru
5-Aminopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines were synthesized via alkylation of
3-cyanopyridine-2(1H)-thiones with 2-(chloromethyl)benzonitrile followed by treatment of
the products with potassium tert-butoxide. The oxidation of the alkylated products to corre-
sponding sulfoxides or sulfones followed by treatment with potassium tert-butoxide provided
the corresponding 11-oxides or 11,11-dioxides.
Key words: 3-cyanopyridine-2(1H)-thiones, 2-(chloromethyl)benzonitrile, potassium tert-
butoxide, domino reactions, 5-aminopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines, sulfoxides,
sulfones, heterocyclization.
Derivatives of fused isoquinolines possess different
kinds of pharmacological activity,1—4 which makes the
design of novel methods for the synthesis of isoquinolines
fused with various carbocyclic or heterocyclic moieties to
be of both theoretical and practical interests.
The present work was aimed at the synthesis of 5-ami-
nopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines using
2-(chloromethyl)benzonitrile as the alkylating agent.
Results and Discussion
We have previously5—9 developed a versatile method
for the synthesis of one type among this family of hetero-
cycles, which consists in the alkylation of nitrile derivatives
containing a hydroxy or a thiol group next to the nitrile
function with 2-(chloromethyl)benzoic acid ester or nitrile
and their subsequent cyclization by the action of potassium
tert-butoxide in anhydrous DMF. In particular, we have
recently8 reported the synthesis of pyrido[3´,2´:4,5]thi-
eno[3,2-c]isoquinoline-5(6H)-one derivatives via alkylation
of substituted 3-cyanopyridine-2(1H)-thiones with methyl
2-(chloromethyl)benzoate and subsequent treatment of
the alkylation products with potassium tert-butoxide.
The reaction of substituted 3-cyanopyridine-2(1H)-
thiones 1a—f with 2-(chloromethyl)benzonitrile 2 was
carried out under conditions similar to that reported,8
viz., reflux of solution in CHCl3 in the presence of
Et3N (Scheme 1). Resulting substituted 2-(2-cyano-
benzylthio)-3-cyanopyridines 3a—f were obtained in
good or very good yields. The treatment with potassium
tert-butoxide (1 equiv.) in DMF caused their hetero-
cyclization into 5-aminopyrido[3´,2´:4,5]thieno[3,2-c]-
isoquinolines 4a—f.
Scheme 1
Compound
1a, 3a, 4a
1b, 3b, 4b
1c, 3c, 4c
R1
Me
H
R2
H
‒(CH2)4‒
‒(CH2)4‒
R3
Me
Compound
R1
Ph
Ph
CF3
R2
H
H
R3
Me
Ph
1d, 3d, 4d
1e, 3e, 4e
1f, 3f, 4f
Ph
H
4-MeOC6H4
Reagents and conditions: i. Et3N (1.5 equiv.), CHCl3, reflux, 40 min; ii. ButOK (1.0 equiv.), DMF, 70—75 °C, 40 min.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 0902—0911, May, 2018.
1066-5285/18/6705-0902 © 2018 Springer Science+Business Media, Inc.

5-Aminopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
903
It seemed also interesting to investigate a possibility of
the synthesis of the related 5-aminopyrido[3´,2´:4,5]-
thieno[3,2-c]isoquinoline derivatives containing an oxi-
dized sulfur atom via the oxidation of sulfides 3 into the
corresponding sulfoxides or sulfones and their subsequent
heterocyclization under the same conditions as that in
preparation of 5-aminobenzothieno[3,2-c]isoquinolines.9
The oxidation of sulfides 3a—f was performed with mono-
peroxymaleic acid (MPMA) at a molar ratio of 1 : 1. This
efficient reagent allowed one to oxidize sulfides into sulf-
oxides under mild conditions (room temperature, 20 min)
and with high selectivity, providing the corresponding
sulfoxides 5a—f in very good yields (Scheme 2). The oxi-
dation of sulfides 3a—f into sulfones 7a—f was also carried
out with MPMA, taken at the molar ratio of 1 : 2.2. The
oxidation proceeded at room temperature within 2—3 h
and gave sulfones 7a—f in high yields.
The cyclization of sulfoxides 5a—f with potassium
tert-butoxide was carried out under the conditions de-
scribed for sulfides 3a—f, and the corresponding 11-oxides
6 were thus obtained (see Scheme 2). However, the yield
of products 6 was essentially dependent on a nature of the
substituents in the starting sulfoxide 5. Thus, sulfoxides
5a,b containing alkyl groups were smoothly cyclized into
products 6a,b, while aryl-substituted derivatives 5d—f
produced large amounts of by-products. The yields of
compounds 6d and 6e were 35 and 28%, respectively, and
there was no desired product formed upon treatment of
sulfoxide 5f with potassium tert-butoxide. From sulfoxide
5c containing a fused cyclohexane moiety in addition to
the phenyl group, the desired product 6c was obtained in
a good yield. In the series of sulfones 7a—f, the corre-
sponding 11,11-dioxides 8a—f were in all cases formed in
the good yields (see Scheme 2).
The structure of compounds 3a—f—8a—f was con-
1
firmed by IR spectroscopy, H and 13C NMR data, and
also 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
2213—2236 cm–1. The absorption bands of the S=O group
in sulfoxides 5a—f are in the region of 1058—1088 cm–1
.
In sulfones 7a—f, the SO2 group manifests two absorption
bands in the regions of 1320—1332 and 1131—1146 cm–1
.
In the 1H NMR spectra of sulfides 3a—f, the signals from
the protons in the CH2S group were found as singlets in
the region of δ = 4.63—4.91. The signals from the protons
in the CH2S(O) group in sulfoxides 5a—f appeared as two
doublets in the regions of δ = 4.52—4.73 and 4.69—4.82
with the spin-spin coupling constants J = 12.5 for 5c and
13.2 Hz for other sulfoxides. The signal from the protons
in the CH2SO2 group in sulfones 7a—f were found as
singlets in the region of δ = 5.11—5.35. The 13C NMR
spectra of compounds 3a—f, 5a—f, and 7a—f contained
signals from the carbon atoms in the CN group at pyridine
cycle in the regions of δ = 110.52—115.76, while this group
in the benzonitrile moiety exhibited the chemical shift
of δ = 116.99—117.64. Apart from that, sulfides 3a—f
were characterized by the presence of a signal from the
carbon atom in the CH2S group at δ = 31.88—32.75,
sulfoxides 5a—f demonstrated a signal from the carbon
atom in the CH2S(O) group with the chemical shift of
δ = 57.10—57.59, while a signal from the carbon atom in
the CH2SO2 group in sulfones 5a—f had the chemical shift
of δ = 56.25—56.60.
Scheme 2
Reagents and conditions: i. MPMA (1.0 equiv.), 20—25 °C, 20 min; ii. MPMA (2.2 equiv.), 20—25 °C, 2—3 h; iii. ButOK (1.0 equiv.),
DMF, 70—75 °C, 40—50 min.

904
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
Kalugin et al.
Scheme 3
n = 0 (3, 4, 9), 1 (5, 6, 10), 2 (7, 8, 11 )
internal standard. 13C (75 MHz) NMR spectra were recorded on
a Bruker AM-300 spectrometer in DMSO-d6.
The IR spectra of heterocyclization products 4a—f,
6a—e, and 8a—f were characterized by the presence of two
or more absorption bands of the NH2 group in the region
of 3207—3488 cm–1. In the IR spectra of sulfoxides
6a—e, the absorption bands of the S=O group were in the
region of 1000—1015 cm–1. The sulfonyl group in hetero-
cycles 8a—f exhibited two absorption bands in the regions
of 1279—1296 and 1129—1152 cm–1. In the 1H NMR
spectra of compounds 4a—f, 6a—e, and 8a—f, the proton
signals of the NH2 groups were observed as broad singlets
at δ = 5.87—7.09 for 4a—f, at 6.80—7.95 for 6a—e, and
at 7.02—8.25 for 8a—f, while the signals from the carbon
atom at the NH2 group in the 13C NMR spectra resonated
at δ = 155.85—156.68 for 4a—f, at 158.58—159.83 for
6a—e, and at 159.35—161.42 for 8a—f.
We believe that the reactions of sulfides 3, sulfoxides 5,
and sulfones 7 with potassium tert-butoxide follow the
same mechanism, which is a domino reaction including
the formation of the corresponding benzothiophene in-
termediates 9, 10, and 11 via the Thorpe—Ziegler reaction
at the first step and their subsequent annulation into com-
pounds 4, 6, and 8 via the Thorpe—Ziegler hetero reaction
(Scheme 3).
In the conclusion, we have reported on the synthesis
of previously unknown 5-aminopyrido[3´,2´:4,5]thieno-
[3,2-c]isoquinolines in good yields via the alkylation of
substituted 3-cyanopyridine-2(1H)-thiones with 2-(chloro-
methyl)benzonitrile and their subsequent heterocycliza-
tion with potassium tert-butoxide. The oxidation of
the alkylated products into the corresponding sulf-
oxides and sulfones with their subsequent treatment
with potassium tert-butoxide allowed one to prepare
the related heterocyclic systems containing an oxidized
sulfur atom.
Starting 3-cyanopyridine-2(1H)-thiones 1a,10 1b,11 1c,12
1d,13 1e,14 1f,15 and 2-(chloromethyl)benzonitrile 216 were pre-
pared according to the reported procedures.
Synthesis of substituted 2-(2-cyanobenzylthio)-3-cyanopyrid-
ines 3a—f (general procedure). Triethylamine (0.84 mL, 6 mmol)
was added to a solution of 3-cyanopyridine-2(1H)-thione 1a—f
(4 mmol) and 2-(chloromethyl)benzonitrile 2 (0.65 g, 4 mmol)
in CHCl3 (5 mL). The reaction mixture was refluxed for 40 min,
then the solvent was evaporated in vacuo, and the product was
isolated by column chromatography (silica gel 60—80 mesh, the
eluent was hexane—CHCl3 = 3 : 2) and crystallized from an
appropriate solvent.
3-Cyano-2-(2-cyanobenzylthio)-4,6-dimethylpyridine (3a).
The yield was 1.04 g (93%), m.p. 131—132 °C (CHCl3—MeOH).
Found (%): C, 69.02; H, 4.53; N, 15.14; S, 11.70. C16H13N3S.
Calculated (%): C, 68.79; H, 4.69; N, 15.04; S, 11.48. IR, ν/cm–1
:
2236 (CN), 2220 (CN), 1584, 1376, 1272, 876, 772. 1H NMR
(DMSO-d6), δ: 2.36 (s, 3 H, 4-Мe); 2.51 (s, 3 H, 6-Мe); 4.66
(s, 2 H, CH2S); 7.09 (s, 1 H, C(5)HPy); 7.44 (t, 1 H, C(5)HBzn
,
J = 7.3 Hz); 7.64 (t, 1 H, C(4)HBzn, J = 7.3 Hz); 7.72 (d, 1 H,
C(3)HBzn, J = 7.3 Hz); 7.81 (d, 1 H, C(6)HBzn, J = 7.3 Hz).
13C NMR (DMSO-d6), δ: 19.67 (4-Мe), 24.15 (6-Мe), 31.90
(CH2S), 103.94 (CPy(3)), 112.18 (CBzn(1)), 114.90 (CNPy), 117.62
(CNBzn), 120.92 (CPy(5)), 128.20 (CBzn(5)), 130.52 (CBzn(3)),
132.89 (CBzn(6)), 133.26 (CBzn(4)), 141.54 (CBzn(2)), 152.75
(CPy(4)), 159.37 (C(Py2)), 161.70 (CPy(6)).*
3-Cyano-2-(2-cyanobenzylthio)-5,6,7,8-tetrahydroquinoline (3b).
The yield was 1.32 g (92%); m.p. 113—113.5 °C (CHCl3—MeOH).
Found (%): C, 70.82; H, 4.88; N, 13.89; S, 10.30. C18H15N3S.
Calculated (%): C, 70.79; H, 4.95; N, 13.76; S, 10.50. IR, ν/cm–1
:
3068, 3038, 2935, 2227 (CN), 2219 (CN), 1583, 1535, 1450, 1414,
1387, 1174, 1039, 771, 754. 1H NMR (DMSO-d6), δ: 1.62—1.73
(m, 2 H, 6-(CH2)THQ)**; 1.75—1.86 (m, 2 H, 7-(CH2)THQ); 2.66
(t, 2 H, 5-(CH2)THQ, J = 5.9 Hz); 2.89 (t, 2 H, 8-(CH2)THQ
J = 5.9 Hz); 4.63 (s, 2 H, CH2S); 7.43 (t, 1 H, C(5)HBzn
,
,
J = 8.1 Hz); 7.63 (t, 1 H, C(4)HBzn, J = 8.1 Hz); 7.70 (d, 1 H,
C(3)HBzn, J = 8.1 Hz); 7.81 (d, 1 H, C(6)HBzn, J = 8.1 Hz); 7.87
(s, 1 H, C(4)HTHQ). 13C NMR (DMSO-d6), δ: 21.64 (6-(CH2)THQ),
21.91 (7-(CH2)THQ), 26.99 (5-(CH2)THQ), 31.80 (8-(CH2)THQ),
Experimental
IR spectra were recorded on a Specord M 80-2 spectrometer
in KBr pellets. 1H (300 MHz) NMR spectra were recorded on
a Bruker AM-300 spectrometer in DMSO-d6 using SiMe4 as an
* Py is the pyridine moiety, Bzn is the benzonitrile moiety.
** THQ is the tetraquinoline fragment.

5-Aminopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
905
32.26 (CH2S), 103.38 (CTHQ(3)), 112.20 (CBzn(1)), 115.76
(CNTHQ), 117.64 (CNBzn), 128.19 (CBzn(5)), 129.16 (CTHQ(4a)),
130.46 (CBzn(3)), 132.96 (CBzn(6)), 133.30 (CBzn(4)), 141.65
(CBzn(2)), 141.95 (CTHQ(4)), 155.67 (CTHQ(2)), 161.93 (CTHQ(8a)).
3-Cyano-2-(2-cyanobenzylthio)-4-phenyl-5,6,7,8-tetrahydro-
quinoline (3c). The yield was 1.91 g (80%); m.p. 167—169 °C
(CHCl3—MeOH). Found (%): C, 75.38; H, 5.11; N, 11.13; S,
8.33. C24H19N3S. Calculated (%): C, 75.56; H, 5.02; N, 11.01;
S, 8.40. IR, ν/cm–1: 3077, 3025, 2944, 2869, 2224 (CN), 1537,
1487, 1420, 1376, 1328, 1280, 1251, 762, 736, 701. 1H NMR
(DMSO-d6), δ: 1.60—1.70 (m, 2 H, 6-(CH2)THQ); 1.76—1.86
(m, 2 H, 7-(CH2)THQ); 2.33 (t, 2 H, 5-(CH2)THQ, J = 5.9 Hz);
2.99 (t, 2 H, 8-(CH2)THQ, J = 5.9 Hz); 4.69 (s, 2 H, CH2S);
(C6-Ph(1)), 140.86 (CBzn(2)), 154.57 (CPy(4)), 158.33 (CPy(6)),
161.37 (CPy(2)).
3-Cyano-2-(2-cyanobenzylthio)-6-(4-methoxyphenyl)-4-(tri-
fluoromethyl)pyridine (3f). The yield was 1.43 g (84%); m.p.
218.5—219 °C (CHCl3—MeOH). Found (%): C, 62.23; H, 3.49;
N, 9.75; S, 7.74. C22H14F3N3OS. Calculated (%): C, 62.11;
H, 3.32; N, 9.88; S, 7.54. IR, ν/cm–1: 2960, 2228 (CN), 1604,
1580, 1548, 1516, 1380, 1256, 1136, 1092, 836, 768. 1H NMR
(DMSO-d6), δ: 3.87 (s, 3 H, OMe); 4.91 (s, 2 H, CH2S); 7.10
(d, 2 H, C(3)H6-Ph(3), C(5)H6-Ph, J = 8.8 Hz); 7.50 (t, 1 H,
C(5)HBzn, J = 7.3 Hz); 7.66 (t, 1 H, C(4)HBzn, J = 7.3 Hz); 7.73
(d, 1 H, C(3)HBzn, J = 8.1 Hz); 7.88 (d, 1 H, C(6)HBzn
J = 7.3 Hz); 8.13 (s, 1 H, C(5)HPy); 8.25 (d, 2 H, C(2)H6-Ph
,
,
7.33 (m, 2 H, C(2)H4-Ph,C(6)H4-Ph); 7.46 (t, 1 H, C(5)HBzn
J = 7.3 Hz); 7.50 (m, 3 H, C(3)H4-Ph, C(4)H4-Ph, C(5)H4-Ph));
7.67 (t, 1 H, C(4)HBzn, J = 8.1 Hz); 7.77 (d, 1 H, C(3)HBzn
,
C(6)H6-Ph, J = 8.1 Hz). 13C NMR (DMSO-d6), δ: 32.62 (CH2S),
55.63 (OМe), 98.51 (CPy(3)), 111.91 (CBzn(1)), 112.26 (q, CPy(5),
J = 4.4 Hz), 113.09 (CNPy), 114.64 (C6-Ph(3), C6-Ph(5)), 117.45
(CNBzn), 121.54 (q, CF3, JCF = 273.1 Hz), 127.89 (C6-Ph(1)),
128.62 (CBzn(5)), 129.97 (CBzn(3)), 130.01 (C6-Ph(2), C6-Ph(6)),
133.41 (CBzn(6)), 133.69 (CBzn(4)), 140.10 (q, CPy(4), J = 35.4 Hz),
140.25 (CBzn(2)), 159.64 (CPy(6)), 162.50 (C6-Ph(4)), 162.89
(CPy(2)).
,
J = 8.1 Hz); 7.83 (d, 1 H, C(6)HBzn, J = 8.1 Hz). 13C NMR
(DMSO-d6), δ: 21.60 (6-(CH2)THQ), 21.75 (7-(CH2)THQ),
26.18 (5-(CH2)THQ), 31.68 (8-(CH2)THQ), 32.75 (CH2S),
103.85 (CTHQ(3)), 112.18 (CBzn(1)), 115.03 (CNTHQ), 117.60
(CNBzn), 127.11 (CTHQ(4a)), 128.04 (C4-Ph(3), C4-Ph(5)), 128.07
(CBzn(5)), 128.70 (C4-Ph(2), C4-Ph(6)), 129.07 (C4-Ph(4)), 130.45
(CBzn(3)), 132.83 (CBzn(6)), 133.21 (CBzn(4)), 134.89 (C4-Ph(1)),
141.65 (CBzn(2)), 153.80 (CTHQ(4)), 156.21 (CTHQ(2)), 161.55
(CTHQ(8a)).
Synthesis of substituted 5-aminopyrido[3´,2´:4,5]thieno[3,2-c]-
isoquinolines 4a—f (general procedure). Potassium tert-butoxide
(0.23 g, 2 mmol) was added to a solution of compound 3a—f
(2 mmol) in anhydrous DMF (5 mL). The reaction mixture was
stirred at 55—60 °C for 40 min and then poured into H2O (20 mL).
The formed crystals were collected by filtration, washed with cold
MeOH, dried, and recrystallized from an appropriate solvent.
5-Amino-7,9-dimethylpyrido[3΄,2΄:4,5]thieno[3,2-c]isoquino-
line (4a). The yield was 0.44 g (79%), m.p. 278—280 °C (DMF—
MeOH). Found (%): C, 68.97; H, 4.88; N, 15.17; S, 11.61.
C16H13N3S. Calculated (%): C, 68.79; H, 4.69; N, 15.04.S, 11.48.
IR, ν/cm–1: 3472, 3436, 3328, 3224 (NH2), 1616, 1568, 1544,
1420, 1324, 756. 1H NMR (DMSO-d6), δ: 2.57 (s, 3 H, 7-Me);
3.02 (s, 3 H, 9-Me); 6.98 (s, 2 H, NH2); 7.14 (s, 1 H, C(8)HPTI);
3-Cyano-2-(2-cyanobenzylthio)-6-methyl-4-phenylpyridine
(3d). The yield was 1.85 g (74%), m.p. 148—150 °C (CHCl3—
MeOH). Found (%): C, 73.98; H, 4.32; N, 12.45; S, 9.51.
C21H15N3S. Calculated (%): C, 73.87; H, 4.43; N, 12.31; S, 9.39.
IR, ν/cm–1: 3057, 2921, 2223 (CN), 2213 (CN), 1578, 1525, 1498,
1275, 1073, 772, 765, 695. 1H NMR (DMSO-d6), δ: 2.61 (s, 3 H,
6-Мe); 4.73 (s, 2 H, CH2S); 7.28 (s, 1 H, C(5)HPy); 7.46 (t, 1 H,
C(5)HBzn, J = 7.3 Hz); 7.50—7.56 (m, 3 H, C(3)H4-Ph(3),
C(4)H4-Ph, C(5)H4-Ph); 7.57—7.63 (m, 2 H, C(2)H4-Ph, C(6)H4-Ph);
7.67 (t, 1 H, C(4)HBzn, J = 7.3 Hz); 7.78 (d, 1 H, C(3)HBzn
,
J = 7.3 Hz); 7.83 (d, 1 H, C(6)HBzn, J = 7.3 Hz). 13C NMR
(DMSO-d6), δ: 24.17 (6-Me), 31.88 (CH2S), 101.64 (CPy(3)),
112.13 (CBzn(1)), 115.35 (CNPy), 117.52 (CNBzn), 119.92 (CPy(5)),
128.07 (CBzn(5)), 128.33 (C4-Ph(3), C4-Ph(5)), 128.80 (C4-Ph(2),
C4-Ph(6)), 129.96 (CBzn(3)), 130.41 (C4-Ph(4)), 132.83 (CBzn(6)),
133.17 (CBzn(4)), 135.36 (C4-Ph(1)), 141.35 (CBzn(2)), 153.34
(CPy(4)), 160.59 (CPh(2)), 162.08 (CPy(6)).
7.61 (t, 1 H, C(3)HPTI, J = 7.3 Hz); 7.79 (t, 1 H, C(2)HPTI,
J = 7.3 Hz); 7.90 (d, 1 H, C(1)HPTI, J = 8.1 Hz); 8.39 (d, 1 H,
C(4)HPTI, J = 7.3 Hz). 13C NMR (DMSO-d6), δ: 18.96 (7-Мe),
23.81 (9-Мe), 116.12 (CPTI(11a)), 116.91 (CPTI(4a)), 122.10
(CPTI(8)), 123.53 (CPTI(4)), 125.20 (CPTI(6b)), 125.38 (CPTI(3)),
126.49 (CPTI(1)), 131.16 (CPTI(2)), 132.07 (CPTI(11b)), 144.08
(CPTI(7)), 144.90 (CPTI(6a)), 156.03 (CPTI(9)), 156.50 (CPTI(5)),
159.85 (CPTI(10a)).*
3-Cyano-2-(2-cyanobenzylthio)-4,6-diphenylpyridine (3e).
The yield was 1.32 g (82%); m.p. 176—177 °C (CHCl3—MeOH).
Found (%): C, 77.22; H, 4.28; N, 10.28; S, 7.70. C26H17N3S.
5-Amino-8,9,10,11-tetrahydroisoquinolino[3΄,4΄:4,5]thieno-
[2,3-b]quinoline (4b). The yield was 0.45 g (74%); m.p. 287—290 °C
(DMF—MeOH). Found (%): C, 70.63; H, 5.05; N, 13.67;
S, 10.61. C18H15N3S. Calculated (%): C, 70.79; H, 4.95; N, 13.76;
S, 10.50. IR, ν/cm–1: 3360, 3256 (NH2), 3144, 2928, 1644, 1616,
1568, 1528, 1424, 1320, 760. 1H NMR (DMSO-d6), δ: 1.70—1.90
(m, 4 H, 9-(CH2)THIQTQ, 10-(CH2)THIQTQ); 2.85—3.02 (m, 4 H,
8-(CH2)THIQTQ, 11-(CH2)THIQTQ); 7.09 (s, 2 H, NH2); 7.60
Calculated (%): C, 77.39; H, 4.25; N, 10.41; S, 7.95. IR, ν/cm–1
:
3056, 2216 (CN), 1568, 1528, 1488, 1368, 776. 1H NMR
(DMSO-d6), δ: 4.91 (s, 2 H, CH2S); 7.47 (t, 1 H, C(5)HBzn
J = 7.3 Hz); 7.50—7.55 (m, 3 H, C(3)H6-Ph, C(4)H6-Ph
,
,
C(5)H6-Ph); 7.56—7.62 (m, 3 H, C(3)H4-Ph,C(4)H4-Ph, C(5)H4-Ph);
7.66 (t, 1 H, C(4)HBzn, J = 8.1 Hz); 7.72—7.78 (m, 3 H, C(3)HBzn
and C(2)H4-Ph, C(6)H4-Ph); 7.90 (d, 1 H, C(6)HBzn, J = 8.1 Hz);
(t, 1 H, C(3)HTHIQTQ, J = 7.3 Hz); 7.77 (t, 1 H, C(2)HTHIQTQ
,
7.93 (s, 1 H, C(5)HPy); 8.20—8.27 (m, 2 H, C(2)H6-Ph
,
J = 8.1 Hz); 7.86 (d, 1 H, C(1)HTHIQTQ, J = 8.1 Hz); 8.06 (s, 1 H,
C(7)HTHIQTQ); 8.39 (d, 1 H, C(4)HTHIQTQ, J = 8.1 Hz). 13C NMR
(DMSO-d6), δ: 22.38 (9-(CH2)THIQTQ), 22.62 (10-(CH2)THIQTQ),
28.39 (8-(CH2)THIQTQ), 32.45 (11-(CH2)THIQTQ), 116.72
C(6)H6-Ph). 13C NMR (DMSO-d6), δ: 32.42 (CH2S), 102.99
(CPy(3)), 111.96 (CBzn(1)), 115.64 (CNPy), 116.88 (CPy(5)), 117.53
(CNBzn), 127.73 (C6-Ph(3), C6-Ph(5)), 128.49 (CBzn(5)), 128.79
(C4-Ph(3), C4-Ph(5)), 129.00 (C4-Ph(2), C4-Ph(6)), 129.08 (C6-Ph(2),
C6-Ph(6)), 129.97 (CBzn(3)), 130.31 (C4-Ph(4)), 131.03 (C6-Ph(4)),
133.35 (CBzn(6)), 133.63 (CBzn(4)), 135.63 (C4-Ph(1)), 136.59
* PTI is pyrido[2΄,3΄,4,5]thieno[3,2-c]isoquinoline.

906
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
Kalugin et al.
(CTHIQTQ(13a)), 117.80 (CTHIQTQ(4a)), 123.59 (CTHIQTQ(4)),
125.50 (CTHIQTQ(3)), 126.48 (CTHIQTQ(1)), 127.67
(CTHIQTQ(6b)), 128.88 (CTHIQTQ(7a)), 129.66 (CTHIQTQ(7)),
131.26 (CTHIQTQ(2)), 132.29 (CTHIQTQ(13b)), 141.99
(CTHIQTQ(6a)), 156.68 (CTHIQTQ(5)), 156.99 (CTHIQTQ(11a)),
157.18 (CTHIQTQ(12a)).*
H
7-Ph); 7.83 (t, 1 H, HPTI(2), J = 7.3 Hz); 7.88 (s, 1 H, HPTI(8));
7.97 (d, 1 H, C(1)HPTI, J = 8.1 Hz); 8.25 (d, 2 H, C(2)H9-Ph
,
C(6)H9-Ph, J = 8.1 Hz); 8.37 (d, 1 H, HPTI(4), J = 8.1 Hz).
13C NMR (DMSO-d6), δ: 117.64 (CPTI(4a)), 117.87 (CPTI(11a)),
119.21 (CPTI(8)), 124.04 (CPTI(4)), 124.59 (CPTI(6b)), 125.50
(CPTI(3)), 127.12 (CPTI(1)), 127.19 (C9-Ph(3), C9-Ph(5)),
127.58 (C7-Ph(3), C7-Ph(5)), 128.64 (C7-Ph(4)), 129.14 (C7-Ph(2),
C7-Ph(6)), 129.70 (C9-Ph(4)), 130.37 (C9-Ph(2), C9-Ph(6)),
131.45 (CPTI(2)), 132.01 (CPTI(11b)), 137.47 (C7-Ph(1)), 138.05
(C9-Ph(1)), 142.66 (CPTI(7)), 147.67 (CPTI(6a)), 154.43 (CPTI(9)),
155.35 (CPTI(5)), 161.73 (CPTI(12a)).
5-Amino-7-phenyl-8,9,10,11-tetrahydroisoquinolino[3΄,4΄:4,5]-
thieno[2,3-b]quinoline (4c). The yield was 0.41 g (54%); m.p.
287—290 °C (DMF—MeOH). Found (%): C, 75.47; H, 5.09;
N, 10.93; S, 8.53. C24H19N3S. Calculated (%): C, 75.56; H, 5.02;
N, 11.01; S, 8.40. IR, ν/cm–1: 3461, 3342, 3236 (NH2), 3058,
2934, 1634, 1614, 1582, 1505, 1429, 1279, 1142, 1129, 758, 695.
1H NMR (DMSO-d6), δ: 1.63—1.75 (m, 2 H, 9-(CH2)THIQTQ);
5-Amino-9-(4-methoxyphenyl)-7-(trifluoromethyl)pyri-
do[3΄,2΄:4,5]thieno[3,2-c]isoquinoline (4f). The yield was 0.545 g
(64%); m.p. 227—230 °C (CHCl3—MeOH). Found (%): C, 62.27;
H, 3.21; N, 9.78; S, 7.75. C22H14F3N3OS. Calculated (%):
C, 62.11; H, 3.32; N, 9.88; S, 7.54. IR, ν/cm–1: 3372, 3336 (NH2),
2928, 1612, 1584, 1576, 1516, 1364, 1240, 1160, 1128, 832, 760.
1H NMR (DMSO-d6), δ: 3.84 (s, 3 H, OMe); 7.00 (s, 2 H, NH2);
7.09 (d, 2 H, C(3)H9-Ph, C(5)H9-Ph, J = 8.8 Hz); 7.68 (t, 1 H,
C(3)HPTI, J = 7.3 Hz); 7.85 (t, 1 H, C(2)HPTI, J = 8.1 Hz); 7.98
1.80—1.92 (m, 2 H, 10-(CH2)THIQTQ); 2.09 (t, 2 H, 8-(CH2)THIQTQ
,
J = 5.9 Hz); 3.06 (t, 2 H, 11-(CH2)THIQTQ, J = 5.9 Hz); 5.87
(s, 2 H, NH2); 7.28 (m, 2 H, C(2)H7-Ph, C(6)H7-Ph); 7.48 (m, 3 H,
C(3)H7-Ph, C(4)H7-Ph, C(5)H7-Ph); 7.57 (t, 1 H, C(3)HTHIQTQ
,
J = 7.3 Hz); 7.77 (t, 1 H, C(2)HTHIQTQ, J = 8.1 Hz); 7.90 (d, 1 H,
C(1)HTHIQTQ, J = 7.3 Hz); 8.27 (d, 1 H, C(4)HTHIQTQ
,
J = 7.3 Hz). 13C NMR (DMSO-d6), δ: 22.24 (9-(CH2)THIQTQ),
22.43 (10-(CH2)THIQTQ), 28.68 (8-(CH2)THIQTQ), 32.93
(11-(CH2)THIQTQ), 116.83 (CTHIQTQ(13a)), 116.86 CTHIQTQ(4a)),
123.51 (CTHIQTQ(4)), 125.24 (CTHIQTQ(3)), 126.42 (CTHIQTQ (1)),
126.95 (CTHIQTQ(6b)), 127.21 (CTHIQTQ(7a)), 127.61 (C7-Ph(3),
C7-Ph(5)), 128.58 (C7-Ph(2), C7-Ph(6)), 130.90 (C7-Ph(4)), 131.85
(CTHIQTQ(13b)), 136.46 (C7-Ph(1)), 142.78 (CTHIQTQ(6a)), 145.76
(CTHIQTQ(7)), 154.76 (CTHIQTQ(11a)), 156.38 (CTHIQTQ(5)),
157.58 (CTHIQTQ(12a)).
(d, 1 H, C(1)HPTI, J = 8.1 Hz); 8.21—8.29 (m, 3 H, C(8)HPTI
,
C(2)H9-Ph, C(6)H9-Ph); 8.43 (d, 1 H, C(4)HPTI, J = 8.1 Hz).
13C NMR (DMSO-d6), δ: 55.45 (OМe), 112.91 (q, CPTI(8),
J = 6.0 Hz), 114.51 (C9-Ph(3), C9-Ph(5)), 117.70 (CPTI(4a)), 118.96
(CPTI(11a)), 122.56 (CPTI(6b)), 123.02 (q, CF3, J = 271.7 Hz),
124.18 (CPTI(4)), 125.47 (CPTI(3)), 127.71 (CPTI(1)), 128.69
(C9-Ph(2), C9-Ph(6)), 129.40 (C9-Ph(1)), 131.45 (CPTI(2)), 131.65
(CPTI(11b)), 132.23 (q, CPTI(7), J = 34.0 Hz), 140.96 (CPTI(6a)),
154.70 (CPTI(9)), 156.23 (CPTI(5)), 161.09 (C9-Ph(4)), 162.09
(CPTI(12a)).
5-Amino-9-methyl-7-phenylpyrido[3΄,2΄:4,5]thieno[3,2-c]-
isoquinoline (4d). The yield was 0.505 g (74%); m.p. 257—259 °C
(DMF—MeOH). Found (%):C, 73.75; H, 4.51; N, 12.26; S, 9.48.
C21H15N3S. Calculated (%): C, 73.87; H, 4.43; N, 12.31; S, 9.39.
IR, ν/cm–1: 3471, 3352, 3209 (NH2), 3074, 3027, 1616, 1576,
1541, 1497, 1421, 1324, 750, 690, 666. 1H NMR (DMSO-d6), δ:
2.67 (s, 3 H, 9-Me); 6.24 (s, 2 H, NH2); 7.24 (s, 1 H, C(8)HPTI);
7.46—7.54 (m, 3 H, C(3)H7-Ph, C(4)H7-Ph, C(5)H7-Ph); 7.60
Preparation of monoperoxymaleic acid (MPMA) solution.
Grounded maleic anhydride (19.6 g, 0.2 mol) was in small por-
tions added to a cold mixture of H2O2 (5.8 g, 0.17 mol) solution
(90%) and ethyl acetate (100 mL) under stirring at 0 °C. The
reaction mixture was stirred at 0—5 °C for 30 min, then warmed
up to room temperature, and stirred for 1 h. The MPMA solution
(120 mL, 1.23 M) was obtained. This stock solution was stored
at –10—5 °C.
(t, 1 H, C(3)HPTI, J = 8.1 Hz); 7.63—7.70 (m, 2 H, C(2)H7-Ph
,
C(6)H7-Ph); 7.80 (t, 1 H, C(2)HPTI, J = 7.3 Hz); 7.94 (d, 1 H,
C(1)HPTI, J = 6.6 Hz); 8.34 (d, 1 H, C(4)HPTI, J = 7.3 Hz).
13C NMR (DMSO-d6), δ: 23.81 (9-Мe), 117.26 (CPTI(11a)),
117.28 (CPTI(4a)), 122.19 (CPTI(8)), 123.16 (CPTI(6b)), 123.63
(CPTI(4)), 125.35 (CPTI(3)), 126.60 (CPTI(1)), 127.28 (C7-Ph(3),
Synthesis of 3-cyano-2-(2-cyanobenzylsulfinyl)pyridines 5a—f
(general procedure). MPMA solution (1.2 M, 2.5 mL, 3 mmol)
in ethyl acetate was added to a solution of compound 3 (3 mmol)
in CHCl3 (10 mL). The reaction mixture was stirred at room
temperature for 20—25 min (TLC monitoring), the acid was
neutralized with aqueous Na2CO3, and the target product was
extracted with CHCl3 (3×20 mL). The extract was dried over
MgSO4, filtered, the solvent was evaporated, and the product
was isolated by chromatography on silica gel (the eluents were
CHCl3—hexane = 2 : 1 and CHCl3). After evaporation of the
eluate, sulfoxide 5 was crystallized from an appropriate solvent.
3-Cyano-2-(2-cyanobenzylsulfinyl)-4,6-dimethylpyridine (5a).
The yield was 0.73 g (83%); m.p.139—140 °C (acetone—ether).
Found (%): C, 64.93; H, 4.58; N, 14.11; S, 10.63. C16H13N3OS.
C
7-Ph(5)), 128.21 (C7-Ph(4)), 129.98 (C7-Ph(2), C7-Ph(6)), 131.07
(CPTI(2)), 131.90 (CPTI(11b)), 137.29 (C7-Ph(1)), 142.33 (CPTI(7)),
146.65 (CPTI(6a)), 155.05 (CPTI(9)), 156.57 (CPTI(5)), 160.80
(CPTI(10a)).
5-Amino-7,9-diphenylpyrido[3΄,2΄:4,5]thieno[3,2-c]isoquin-
oline (4e). The yield was 0.58 g (72%), m.p. 232—234 °C (DMF—
MeOH). Found (%): C, 77.22; H, 4.28; N, 10.28; S, 7.70.
C26H17N3S. Calculated (%): C, 77.39; H, 4.25; N, 10.41; S, 7.95.
IR, ν/cm–1: 3408, 3376, 3240, 3216 (NH2), 3048, 1632, 1624,
1616, 1568, 1536, 1448, 1416, 1324, 752. 1H NMR (DMSO-d6),
δ: 6.38 (s, 2 H, NH2); 7.45—7.60 (m, 6 H, C(3)H9-Ph, C(4)H9-Ph
,
Calculated (%): C, 65.07; H, 4.44; N, 14.23; S, 10.85. IR, ν/cm–1
:
C(5)H9-Ph, C(3)H7-Ph, C(4)H7-Ph, C(5)H7-Ph); 7.63 (t, 1 H,
2232 (CN), 1596, 1448, 1336, 1088, 1072 (S=O), 780. 1H NMR
(DMSO-d6), δ: 2.40 (s, 3 H, 4-Me); 2.53 (s, 3 H, 6-Me); 4.54
(d, 1 H, CH2S(O), J = 13.2 Hz); 4.69 (d, 1 H, CH2S(O),
J = 13.2 Hz); 7.35 (d, 1 H, C(3)HBzn, J = 8.1 Hz); 7.52 (t, 1 H,
C(5)HBzn, J = 7.3 Hz); 7.55 (s, 1 H, C(5)HPy); 7.65 (t, 1 H,
C(4)HBzn, J = 8.1 Hz); 7.75 (d, 1 H, C(6)HBzn, J = 8.1 Hz).
C(3)HPTI, J = 8.1 Hz); 7.72—7.82 (m, 2 H, C(2)H7-Ph, C(6)
* THIQTQ is tetrahydroisoquinolino[3΄,4΄,4,5]thieno[2,3-b]-
quinoline.

5-Aminopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
907
13C NMR (DMSO-d6), δ: 19.59 (4-Мe), 24.03 (6-Мe), 57.12
(CH2SO), 106.33 (CPy(3)), 112.38 (CBzn(1)), 112.81 (CNPy),
117.15 (CNBzn), 126.38 (CPy(5)), 129.24 (CBzn(5)), 132.28
(CBzn(3)), 133.05 (CBzn(6)), 133.12 (CBzn(4)), 133.41 (d, CBzn(2),
J = 6.6 Hz), 154.02 (CPy(4)), 162.38 (CPy(6)), 162.73 (CPy(2)).
3-Cyano-2-(2-cyanobenzylsulfinyl)-5,6,7,8-tetrahydroquino-
line (5b). The yield was 0.72 g (74%); m.p.137—139 °C (acetone—
ether). Found (%): C, 67.40; H, 4.59; N, 13.21; S, 10.14.
C18H15N3OS. Calculated (%): C. 67.27; H, 4.70; N, 13.07; S, 9.98.
IR, ν/cm–1: 2936, 2920, 2224 (CN), 1416, 1072 (S=O), 772.
1H NMR (DMSO-d6), δ: 1.70—1.80 (m, 2 H, 6-(CH2)THQ);
132.26 (CBzn(2)), 132.96 (CBzn(6)), 133.06 (CBzn(4)), 134.84
(C4-Ph(1)), 154.08 (CPy(4)), 163.16 (CPy(6)), 163.57 (CPy(2)).
3-Cyano-2-(2-cyanobenzylsulfinyl)-4,6-diphenylpyridine (5e).
The yield was 0.88 g (70%); m.p. 189.5—191 °C (acetone—ether).
Found (%): C, 74.55; H, 4.19; N, 9.87; S, 7.38. C26H17N3OS.
Calculated (%): C, 74.44; H, 4.08; N, 10.02; S, 7.64. IR, ν/cm–1
:
2216 (CN), 1568, 1524, 1488, 1368, 1064 (S=O), 760. 1H NMR
(DMSO-d6), δ: 4.73 (d, 1 H, CH2S(O), J = 13.2 Hz); 4.82 (d, 1 H,
CH2S(O), J = 13.2 Hz); 7.47 (d, 1 H, C(3)HBzn, J = 7.3 Hz);
7.49—7.57 (m, 4 H, C(4)HBzn and C(3)H6-Ph, C(4)H6-Ph, C(5)
H6-Ph); 7.57—7.62 (m, 3 H, C(3)H4-Ph, C(4)H4-Ph, C(5)H4-Ph);
7.63—7.73 (m, 3 H, C(4)HBzn and C(2)H4-Ph, C(6)H4-Ph); 7.88
1.80—1.90 (m, 2 H, 7-(CH2)THQ); 2.81 (t, 2 H, 5-(CH2)THQ
,
J = 5.9 Hz); 2.90 (t, 2 H, 8-(CH2)THQ, J = 5.9 Hz); 4.52 (d, 1 H,
CH2S(O), J = 13.2 Hz); 4.69 (d, 1 H, CH2S(O), J = 13.2 Hz);
(d, 1 H, C(6)HBzn, J = 8.1 Hz); 8.17—8.23 (m, 2 H, C(2)H6-Ph,
C(6)H6-Ph); 8.33 (s, 1 H, C(5)HPy). 13C NMR (DMSO-d6),
δ: 57.51 (CH2SO), 105.18 (CPy(3)), 113.05 (CBzn(1)), 113.27
(CNPy), 117.26 (CNBzn), 122.27 (CPy(5)), 128.07 (C6-Ph(3),
C6-Ph(5)), 129.00 (C4-Ph(3), C4-Ph(5)), 129.11 (C4-Ph(2), C4-Ph(6)),
129.16 (C6-Ph(2), C6-Ph(6)), 129.41 (CBzn(5)), 130.52 (C4-Ph(4)),
131.54 (C6-Ph(4)), 132.52 (CBzn(2), CBzn(3)), 133.22 (CBzn(6)),
133.33 (CBzn(4)), 135.20 (C6-Ph(1)), 135.83 (C4-Ph(1)), 155.58
(CPy(4) Py), 159.05 (CPy(6)), 164.42 (CPy(2)).
3-Cyano-2-(2-cyanobenzylsulfinyl)-6-(4-methoxyphenyl)-4-
(trifluoromethyl)pyridine (5f). The yield was 0.89 g (67%); m.p.
218—220 °C (acetone—ether). Found (%): C, 60.03; H, 3.29;
N, 9.39; S, 7.15. C22H14F3N3O2S. Calculated (%): C, 59.86; H, 3.20;
N, 9.52; S, 7.26. IR, ν/cm–1: 2960, 2224 (CN), 1608, 1576, 1544,
1480, 1376, 1288, 1272, 1256, 1188, 1136, 1088 (S=O), 1024, 768.
1H NMR (DMSO-d6), δ: 3.89 (s, 3 H, OMe); 4.69 (d, 1 H,
CH2S(O), J = 13.2 Hz); 4.82 (d, 1 H, CH2S(O), J = 13.2 Hz);
7.11 (d, 2 H, C(3)H6-Ph, C(5)H6-Ph, J = 8.8 Hz); 7.45 (d, 1 H,
C(3)HBzn, J = 8.1 Hz); 7.54 (t, 1 H, C(5)HBzn, J = 8.1 Hz); 7.68
(t, 1 H, C(4)HBzn, J = 7.3 Hz); 7.76 (d, 1 H, C(6)HBzn, J = 8.1 Hz);
8.24 (d, 2 H, C(2)H6-Ph, C(6)H6-Ph), J = 8.8 Hz); 8.57 (s, 1 H,
C(5)HPy). 13C NMR (DMSO-d6), δ: 55.80 (OMe), 57.59
(CH2SO), 100.20 (CPy(3)), 110.52 (CNPy), 112.96 (CBzn(1)),
114.82 (C6-Ph(3), C6-Ph(5)), 117.17 (CNBzn), 117.80 (q, CPy(5),
J = 4.4 Hz), 121.76 (q, CF3, JCF = 273.1 Hz), 127.27 (C6-Ph(1)),
129.52 (CBzn(5)), 130.46 (C6-Ph(2), C6-Ph(6)), 132.11 (CBzn(2)),
132.64 (CBzn(3)), 133.22 (CBzn(6)), 133.37 (CBzn(4)), 141.28
(q, CPy(4), J = 34.2 Hz), 160.29 (CPy(6)), 162.97 (C6-Ph(4)),
166.11 (CPy(2)).
7.37 (d, 1 H, C(3)HBzn, J = 7.3 Hz); 7.52 (t, 1 H, C(5)HBzn
,
J = 7.3 Hz); 7.65 (t, 1 H, C(4)HBzn, J = 8.1 Hz); 7.75 (d, 1 H,
C(6)HBzn, J = 7.3 Hz); 8.06 (s, 1 H, C(4)HTHQ). 13C NMR
(DMSO-d6), δ: 21.34 (6-(CH2)THQ), 21.71 (7-(CH2)THQ), 27.60
(5-(CH2)THQ), 32.21 (8-(CH2)THQ), 57.10 (CH2SO), 105.29
(CTHQ(3)), 112.75 (CBzn(1)), 113.58 (CNTHQ), 117.09 (CNBzn),
129.23 (CBzn(5)), 132.11 (CBzn(2)), 132.32 (CBzn(3)), 133.07
(CBzn(6)), 133.12 (CBzn(4)), 135.70 (CTHQ(4a)), 143.26
(CTHQ(4)), 159.22 (CTHQ(2)), 162.70 (CTHQ(8a)).
3-Cyano-2-(2-cyanobenzylsulfinyl)-4-phenyl-5,6,7,8-tetra-
hydroquinoline (5c). The yield was 0.96 g (81%); m.p. 161—162 °C
(acetone—ether). Found (%): C, 72.35; H, 4.73; N, 10.71; S, 8.19.
C24H19N3OS. Calculated (%): C, 72.52; H 4.82; N 10.57; S 8.07.
IR, ν/cm–1: 3061, 2941, 2867, 2222 (CN), 1556, 1489, 1422,
1
1382, 1084, 1068 (S=O), 768, 730, 701. H NMR (DMSO-d6),
δ: 1.62—1.73 (m, 2 H, 6-(CH2)THQ); 1.78—1.90 (m, 2 H, 7-(CH2)
THQ); 2.44 (t, 2 H, 5-(CH2)THQ, J = 5.9 Hz); 2.97 (t, 2 H,
8-(CH2)THQ, J = 5.9 Hz); 4.60 (d, 1 H, CH2S(O), J = 12.5 Hz);
4.69 (d, 1 H, CH2S(O), J = 12.5 Hz); 7.18—7.30 (m, 2 H, C(2)
H4-Ph, C(6)H4-Ph); 7.43 (d, 1 H, C(3)HBzn, J = 7.3 Hz); 7.50—7.58
(m, 4 H, C(5)HBzn and C(3)H4-Ph, C(4)H4-Ph, C(5)H4-Ph); 7.68
(t, 1 H, C(4)HBzn, J = 7.3 Hz); 7.82 (d, 1 H, C(6)HBzn
,
J = 7.3 Hz). 13C NMR (DMSO-d6), δ: 21.43 (6-(CH2)THQ),
21.51 (7-(CH2)THQ), 27.07 (5-(CH2)THQ), 32.81 (8-(CH2)THQ),
57.32 (CH2SO), 105.92 (CPy(3)), 112.46 (CBzn(1)), 112.72
(CNPy), 116.99 (CNBzn), 127.89 (d, C4-Ph(3), C4-Ph(5),
J = 5.5 Hz), 128.82 (C4-Ph(2), C4-Ph(6)), 129.11 (C4-Ph(4)), 129.22
(CBzn(5)), 132.22 (d, CBzn(2), J = 6.6 Hz), 132.31 (CBzn(3)),
132.97 (CBzn(6)), 133.08 (CBzn(4)), 133.69 (CTHQ(4a)), 134.33
(C4-Ph(1)), 154.36 (CTHQ(4)), 159.44 (CTHQ(2)), 162.58
(CTHQ(8a)).
Synthesis of 3-cyano-2-(2-cyanobenzylsulfonyl)pyridines 7a—f
(general procedure). MPMA solution (1.2 M, 5.5 mL, 6.6 mmol)
in ethyl acetate was added to a solution of compound 3 (3 mmol)
in CHCl3 (10 mL). The reaction mixture was stirred at room
temperature for 2—3 h (TLC monitoring), the acid was neutral-
ized with aqueous Na2CO3, and the target product was extracted
with CHCl3 (3×20 mL). The extract was dried over MgSO4,
filtered, the solvent was evaporated, and the product was crystal-
lized from an appropriate solvent.
3-Cyano-2-(2-cyanobenzylsulfinyl)-6-methyl-4-phenylpyridine (5d).
The yield was 1.0 g (94%), m.p. 156—158 °C (acetone—hexane).
Found (%): C, 70.68; H, 4.17; N, 11.91; S, 8.81. C21H15N3OS.
Calculated (%): C, 70.57; H, 4.23; N, 11.76; S, 8.97. IR,
ν/cm–1: 3060, 2226 (CN), 1584, 1511, 1490, 1081, 1058 (S=O),
783, 775, 714. 1H NMR (DMSO-d6), δ: 2.64 (s, 3 H, 6-Мe);
4.65 (d, 1 H, CH2S(O), J = 13.2 Hz); 4.73 (d, 1 H, CH2S(O),
J = 13.2 Hz); 7.43 (d, 1 H, C(3)HBzn, J = 7.3 Hz); 7.49—7.61
(m, 6 H, C(5)HBzn and C(4)Ph); 7.68 (t, 1 H, C(4)HBzn, J = 7.3 Hz);
7.71 (s, 1 H, C(5)HPy); 7.77 (d, 1 H, C(6)HBzn, J = 7.3 Hz).
13C NMR (DMSO-d6), δ: 24.12 (6-Мe), 57.27 (CH2SO), 104.22
(CPy(3)), 112.71 (CBzn(1)), 112.87 (CNPy), 116.99 (CNBzn),
125.78 (CPy(5)), 128.53 (C4-Ph(3), C4-Ph(5)), 128.85 (C4-Ph(2),
C4-Ph(6)), 129.12 (CBzn(5)), 130.14 (C4-Ph(4)), 132.18 (CBzn(3)),
3-Cyano-2-(2-cyanobenzylsulfonyl)-4,6-dimethylpyridine (7a).
The yield was 0.67 g (72%); m.p.182—183 °C (CHCl3—MeOH).
Found (%): C, 61.95; H, 4.29; N, 13.38; S, 10.41. C16H13N3O2S.
Calculated (%): C, 61.72; H, 4.21; N, 13.50; S, 10.30. IR, ν/cm–1
:
2952, 2236 (CN), 1592, 1324 (SO2), 1148, 1132 (SO2), 768.
1H NMR (DMSO-d6), δ: 2.52 (s, 3 H, 4-Me); 2.62 (s, 3 H, 6-Me);
5.16 (s, 2 H, CH2SO2); 7.55—7.64 (m, 2 H, C(3)HBzn, C(5)
HBzn); 7.72 (t, 1 H, C(4)HBzn, J = 7.3 Hz); 7.77 (s, 1 H, C(5)
HPy); 7.87 (d, 1 H, C(6)HBzn, J = 8.1 Hz). 13C NMR (DMSO-d6),

908
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
Kalugin et al.
δ: 20.27 (4-Мe), 24.05 (6-Мe), 56.25 (CH2SO2), 105.30 (CPy(3)),
112.68 (CBzn(1)), 114.08 (CNPy), 117.32 (CNBzn), 128.63 (CPy(5)),
130.02 (CBzn(5)), 130.76 (CBzn(2)), 133.07 (CBzn(3)), 133.48
(CBzn(6)), 133.56 (CBzn(4)), 155.43 (CPy(4)), 156.44 (CPy(2)),
162.35 (CPy(6)).
3-Cyano-2-(2-cyanobenzylsulfonyl)-4,6-diphenylpyridine (7e).
The yield was 1.02 g (78%); m.p. 216—217 °C (CHCl3—MeOH).
Found (%): C, 71.93; H, 4.09; N, 9.77; S, 7.15. C26H17N3O2S.
Calculated (%): C, 71.71; H, 3.95; N, 9.65; S, 7.36. IR, ν/cm–1
:
3072, 2232 (CN), 1580, 1432, 1328 (SO2), 1144 (SO2), 756.
1H NMR (DMSO-d6), δ: 5.35 (s, 2 H, CH2SO2); 7.49—7.68 (m,
8 H, C(3)HBzn, C(5)HBzn, C(3)H6-Ph, C(4)H6-Ph, C(5)H6-Ph
and C(3)H4-Ph, C(4)H4-Ph, C(5)H4-Ph); 7.70—7.78 (m, 3 H,
3-Cyano-2-(2-cyanobenzylsulfonyl)-5,6,7,8-tetrahydroquino-
line (7b). The yield was 0.65 g (64%); m.p.188—189 °C (CHCl3—
MeOH). Found (%): C, 64.21; H, 4.59; N, 12.54; S, 9.37.
C18H15N3O2S. Calculated (%): C, 64.08; H, 4.48; N, 12.45;
S, 9.50. IR, ν/cm–1: 2960, 2232 (CN), 1320 (SO2), 1140 (SO2),
760. 1H NMR (DMSO-d6), δ: 1.72—1.82 (m, 2 H, 6-(CH2)THQ);
C(4)HBzn and C(2)H4-Ph, C(6)H4-Ph); 7.92 (d, 1 H, C(6)HBzn
,
J = 8.1 Hz); 8.31 (m, 2 H, C(2)H6-Ph, C(6)H6-Ph); 8.51 (s, 1 H,
C(5)HPy). 13C NMR (DMSO-d6), δ: 56.41 (CH2SO2), 103.82
(CPy(3)), 113.19 (CNPy), 114.25 (CBzn(1)), 117.23 (CNBzn), 124.06
(CPy(5)), 128.12 (C6-Ph(3), C6-Ph(5)), 128.96 (C4-Ph(3), C4-Ph(5)),
129.15 (C4-Ph(2), C4-Ph(6)), 129.27 (C6-Ph(2), C6-Ph(6)), 130.00
(CBzn(5)), 130.43 (CBzn(2)), 130.54 (C4-Ph(4)), 131.81 (C6-Ph(4)),
133.17 (CBzn(3)), 133.44 (CBzn(6)), 133.52 (CBzn(4)), 135.08
(C6-Ph(1)), 135.14 (C4-Ph(1)), 157.10 (CPy(4)), 158.15 (CPy(2)),
158.38 (CPy(6)).
1.82—1.93 (m, 2 H, 7-(CH2)THQ); 2.87 (t, 2 H, 5-(CH2)THQ
,
J = 5.9 Hz); 2.98 (t, 2 H, 8-(CH2)THQ, J = 5.9 Hz); 5.11 (s, 2 H,
CH2SO2); 7.55—7.63 (m, 2 H, C(3)HBzn, C(5)HBzn); 7.73 (t, 1 H,
HBzn(4), J = 7.3 Hz); 7.86 (d, 1 H, HBzn(6), J = 7.3 Hz);
8.30 (s, 1 H, C(4)HTHQ). 13C NMR (DMSO-d6), δ: 21.23
(6-(CH2)THQ), 21.54 (7-(CH2)THQ), 27.31 (5-(CH2)THQ), 32.65
(8-(CH2)THQ), 56.31 (CH2SO2), 104.39 (CPy(3)), 113.70 (CNPy),
113.82 (CBzn(1)), 117.00 (CNBzn), 129.70 (CBzn(5)), 130.76
(CBzn(2)), 132.90 (CBzn(3)), 133.23 (CBzn(6)), 133.28 (CBzn(4)),
138.20 (CTHQ(4a)), 144.11 (CTHQ(4)), 155.68 (CTHQ(2)), 161.97
(CTHQ(8a)).
3-Cyano-2-(2-cyanobenzylsulfonyl)-6-(4-methoxyphenyl)-4-
(trifluoromethyl)pyridine (7f). The yield was 1.03 g (75%), m.p.
228—230 °C (CHCl3—MeOH). Found (%): C, 58.03; H, 3.16;
N, 9.05; S, 6.95. C22H14F3N3O3S. Calculated (%): C, 57.77;
H, 3.08; N, 9.19; S, 7.01. IR, ν/cm–1: 2952, 2232 (CN), 1592,
1540, 1416, 1384, 1320 (SO2), 1260, 1180, 1144 (SO2). 1H NMR
(DMSO-d6), δ: 3.90 (s, 3 H, OMe); 5.34 (s, 2 H, CH2SO2); 7.14
(d, 2 H, C(3)H6-Ph, C(5)H6-Ph, J = 8.8 Hz); 7.60—7.70 (m, 2 H,
C(3)HBzn, C(5)HBzn); 7.78 (t, 1 H, C(4)HBzn, J = 7.3 Hz);
3-Cyano-2-(2-cyanobenzylsulfonyl)-4-phenyl-5,6,7,8-tetra-
hydroquinoline (7c). The yield was 0.92 g (75%), m.p. 208—209 °C
(CHCl3—MeOH). Found (%): C, 69.87; H, 4.69; N, 10.10;
S, 7.84. C24H19N3O2S. Calculated (%): C, 69.71; H, 4.63; N, 10.16;
S, 7.75. IR, ν/cm–1: 3092, 2949, 2930, 2867, 2231 (CN), 1558,
1425, 1381, 1332 (SO2), 1146 (SO2), 783, 708. 1H NMR
(DMSO-d6), δ: 1.63—1.75 (m, 2 H, 6-(CH2)THQ); 1.80—1.92
(m, 2 H, 7-(CH2)THQ); 2.47 (t, 2 H, 5-(CH2)THQ, J = 5.9 Hz);
3.05 (t, 2 H, 8-(CH2)THQ, J = 5.9 Hz); 5.18 (s, 2 H, CH2SO2);
7.30—7.36 (m, 2 H, C(2)H4-Py, C(6)H4-Py); 7.52—7.61 (m, 4 H,
C(5)HBzn(5) and C(3)H4-Ph, C(4)H4-Ph, C(5)H4-Ph); 7.66 (d, 1 H,
HBzn(3), J = 8.8 Hz); 7.77 (t, 1 H, C(4)HBzn, J = 8.1 Hz);
7.91 (d, 1 H, C(6)HBzn, J = 7.3 Hz). 13C NMR (DMSO-d6), δ:
21.30 (6-(CH2)THQ), 21.33 (7-(CH2)THQ), 27.37 (5-(CH2)THQ),
32.71 (8-(CH2)THQ), 56.36 (CH2SO2), 104.75 (CPy(3)),
112.53 (CBzn(1)), 113.85 (CNPy), 117.12 (CNBzn), 127.96
(C4-Ph(3), C4-Ph(5)), 128.91 (C7-Ph(2), C4-Ph(6)), 129.42
(C4-Ph(4)), 129,76 (CBzn(5)), 130.85 (CBzn(2)), 132.97 (CBzn(3)),
133.30 (CBzn(6)), 133.34 (CBzn(4)), 134.32 (C4-Ph(1)), 136.27
(CTHQ(4a)), 155.68 (CTHQ(4)), 161.97 (CTHQ(8a)), 164.28
(CTHQ(2)).
7.91 (d, 1 H, C(6)HBzn, J = 8.1 Hz); 8.35 (d, 2 H, C(2)H6-Ph
,
C(6)H6-Ph, J = 8.8 Hz); 8.77 (s, 1 H, C(5)HPy). 13C NMR
(DMSO-d6), δ: 55.74 (OМe), 56.60 (CH2SO2), 100.29 (CPy(3)),
110.77 (CBzn(1)), 114.16 (CNPy), 114.88 (C6-Py(3), C6-Py(5)),
117.16 (CNBzn), 119.88 (q, CPy(5), J = 4.4 Hz), 121.23
(q, CF3, JCF
= 273.2 Hz), 126.70 (C6-Ph(1)), 130.11
(CBzn(5)), 130.62 (C6-Ph(2), C6-Ph(6)), 130.67 (CBzn(2)), 133.22
(CBzn(3)), 133.51 (CBzn(6)), 133.57 (CBzn(4)), 142.61 (q,
CPy(4), J = 33.2 Hz), 158.71 (CPy(2)), 160.20 (CPy(6)), 163.19
(C6-Ph(4)).
Synthesis of substituted 5-aminopyrido[3´,2´:4,5]thieno[3,2-c]-
isoquinoline 11-oxides 6a—e (general procedure). Potassium
tert-butoxide (0.23 g, 2 mmol) was added to a solution of com-
pound 5a—f (2 mmol) in anhydrous DMF (4 mL). The reaction
mixture was stirred at 55—60 °C for 50 min and then poured into
H2O (20 mL). The product was extracted with CHCl3 (3×15
mL). The combined extract was washed with H2O (3×20 mL),
dried over MgSO4, the solvent was evaporated, and the target
product was purified by chromatography on silica gel (the eluent
was CHCl3). After evaporation of the eluate, the compound was
crystallized from an appropriate solvent.
3-Cyano-2-(2-cyanobenzylsulfonyl)-6-methyl-4-phenylpyrid-
ine (7d). The yield was 1.04 g (93%), m.p. 190—192 °C (CHCl3—
MeOH). Found (%): C, 67.68; H, 4.12; N, 11.18; S, 8.71.
C
21H15N3O2S. Calculated (%): C, 67.54; H, 4.05; N, 11.25;
S, 8.59. IR, ν/cm–1: 3077, 3001, 2923, 2225 (CN), 1591, 1491, 1453,
1325 (SO2), 1131 (SO2), 1043, 778, 698. 1H NMR (DMSO-d6),
δ: 2.72 (s, 3 H, 6-Мe); 5.23 (s, 2 H, CH2SO2); 7.55—7.65 (m, 6 H,
C(5)HBzn, C(4)Ph); 7.68 (d, 1 H, C(3)HBzn, J = 7.3 Hz); 7.76
(t, 1 H, C(4)HBzn, J = 6.6 Hz); 7.88 (d, 1 H, C(6)HBzn, J = 6.6 Hz);
7.90 (s, 1 H, C(5)HPy). 13C NMR (DMSO-d6), δ: 23.90 (6-Me),
56.26 (CH2SO2), 102.93 (CPy(3)), 112.88 (CBzn(1)), 113.76
(CNPy), 117.06 (CNBzn), 127.80 (CPy(5)), 128.66 (C4-Ph(3),
C4-Ph(5)), 128.84 (C4-Ph(2), C4-Ph(6)), 129.80 (CBzn(5)), 130.32
(C4-Ph(4)), 130.38 (CBzn(2)), 132.86 (CBzn(3)), 133.27 (CBzn(4),
CBzn(6)), 134.62 (C4-Ph(1)), 155.60 (CPy(4)), 157.03 (CPy(2)),
162.84 (CPy(6)).
5-Amino-7,9-dimethylpyrido[3΄,2΄:4,5]thieno[3,2-c]isoquino-
line 11-oxide (6a). The yield was 0.40 g (67%); m.p. 272—274 °C
(DMF—MeOH). Found (%): C, 64.81; H, 4.36; N, 14.12;
S, 10.97. C16H13N3OS. Calculated (%): C, 65.07; H, 4.44; N, 14.23;
S, 10.85. IR, ν/cm–1: 3344, 3240 (NH2), 3168, 2920, 1632, 1616,
1592, 1568, 1544, 1504, 1420, 1368, 1000 (S=O), 968, 752.
1H NMR (DMSO-d6), δ: 2.51 (s, 3 H, 7-Me); 2.82 (s, 3 H,
9-Me); 7.23 (s, 1 H, C(8)HPTI); 7.55 (t, 1 H, C(3)HPTI
,
J = 7.3 Hz); 7.78 (t, 1 H, C(2)HPTI, J = 7.3 Hz); 7.81 (s, 2 H,
NH2); 7.97 (d, 1 H, C(1)HPTI, J = 8.1 Hz); 8.31 (d, 1 H, C(4)
HPTI, J = 8.1 Hz). 13C NMR (DMSO-d6), δ: 18.48 (7-Me), 23.53

5-Aminopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
909
(9-Me), 116.10 (CPTI(4a)), 118.91 (CPTI(11a)), 122.43 (CPTI(4)),
125.47 (CPTI(3)), 126.53 (CPTI(6b)), 126.76 (CPTI(1)), 128.26
(CPTI(8)), 132.51 (CPTI(2)), 133.83 (CPTI(11b)), 146.01
(CPTI(6a)), 151.20 (CPTI(7)), 158.58 (CPTI(5)), 160.75 (CPTI(9)),
166.06 (CPTI(10a)).
δ: 23.46 (9-Мe), 116.50 (CPTI(4a)), 119.37 (CPTI(11a)),
122.49 (CPTI(4)), 125.12 (CPTI(6b)), 125.41 (CPTI(3)), 126.80
(CPTI(1)), 127.54 (C7-Ph(3), C7-Ph(5)), 127.85 (CPTI(8)),
128.72 (C7-Ph(4)), 129.85 (C7-Ph(2), C7-Ph(6)), 132.31 (CPTI(2)),
133.73 (CPTI(11b)), 136.10 (C7-Ph(1)), 147.32 (CPTI(6a)),
149.89 (CPTI(7)), 158.78 (CPTI(9)), 159.83 (CPTI(5)), 167.33
(CPTI(10a)).
5-Amino-8,9,10,11-tetrahydroisoquinolino[3΄,4΄:4,5]thieno-
[2,3-b]quinoline 13-oxide (6b). The yield was 0.39 g (63%); m.p.
288—290 °C (DMF—MeOH). Found (%): C, 67.45; H, 4.77;
N, 12.88; S, 9.83. C18H15N3OS. Calculated (%): C, 67.27;
H, 4.70; N, 13.07; S, 9.98. IR, ν/cm–1: 3328, 3264, 3216 (NH2),
2920, 2952, 1640, 1616, 1568, 1536, 1504, 1432, 1388, 1000
(S=O), 768. 1H NMR (DMSO-d6), δ: 1.70—1.80 (m, 2 H,
9-(CH2)THQ); 1.80—1.90 (m, 2 H, 10-(CH2)THQ); 2.83—2.98
5-Amino-7,9-diphenylpyrido[3΄,2΄:4,5]thieno[3,2-c]isoquino-
line 11-oxide (6e). The yield was 0.23 g (27%); m.p. 182—186 °C
(DMF—MeOH). Found (%): C, 74.58; H, 4.01; N, 9.91; S, 7.77.
C26H17N3OS. Calculated (%): C, 74.44; H, 4.08; N, 10.02;
S, 7.64. IR, ν/cm–1: 3444, 3426, 3319 (NH2), 3207, 3057, 2906,
1640, 1615, 1588, 1576, 1542, 1502, 1417, 1359, 1027, 1015 (S=O),
759, 696. 1H NMR (DMSO-d6), δ: 7.36 (br.s, 1 H, NH2);
(m, 4 H, 8-(CH2)THQ, 11-(CH2)THQ); 7.58 (t, 1 H, C(3)HTHIQTQ
,
J = 8.1 Hz); 7.76—7.83 (m, 2 H, C(2)HTHIQTQ, C(7)HTHIQTQ);
7.95 (s, 2 H, NH2); 8.00 (d, 1 H, C(1)HTHIQTQ, J = 8.1 Hz);
8.44 (d, 1 H, C(4)HTHIQTQ, J = 8.8 Hz). 13C NMR (DMSO-d6),
δ: 21.91 (9-(CH2)THIQTQ), 22.34 (10-(CH2)THIQTQ), 28.58
(8-(CH2)THIQTQ), 32.18 (11-(CH2)THIQTQ), 117.02 (CTHIQTQ(4a)),
119.86 (CTHIQTQ(13a)), 122.49 (CTHIQTQ(4)), 125.59 (CTHIQTQ(3)),
126.86 (CTHIQTQ(1)), 129.33 (CTHIQTQ(6b)), 130.54 (CTHIQTQ(7)),
132.62 (CTHIQTQ(2)), 133.76 (CTHIQTQ(13b)), 135.82 (CTHIQTQ(7a)),
149.04 (CTHIQTQ(6a)), 158.73 (CTHIQTQ(5)), 161.31 (CTHIQTQ(11a)),
163.14 (CTHIQTQ(12a)).
7.51—7.63 (m, 7 H, C(3)H9-Ph,C(4)H9-Ph, C(5)H9-Ph, C(3)H7-Ph,
C(4)H7-Ph, C(5)H7-Ph and HPTI(3)); 7.74—7.81 (m, 2 H, C(2)
H7-Ph, C(6)H7-Ph); 7.85 (t, 1 H, C(2)HPTI, J = 7.3 Hz); 8.05
(s, 1 H, C(8)HPTI); 8.11 (d, 1 H, C(1)HPTI, J = 7.3 Hz); 8.26—8.34
(m, 2 H, C(2)H9-Ph, C(6)H9-Ph); 8.38 (d, 1 H, C(4)HPTI
,
J = 7.3 Hz). 13C NMR (DMSO-d6), δ: 116.62 (CPTI(4a)),
120.10 (CPTI(11a)), 122.59 (CPTI(4)), 124.61 (CPTI(8)), 125.40
(CPTI(3)), 126.30 (CPTI(6b)), 126.89 (CPTI(1)), 127.00
(C9-Ph(3), C9-Ph(5)), 127.52 (C7-Ph(3), C7-Ph(5)), 128.84
(C7-Ph(4)), 128.94 (C7-Ph(2), C7-Ph(6)), 129.97 (C9-Ph(4)),
130.05 (C9-Ph(2), C9-Ph(6)), 132.33 (CPTI(2)), 133.63 (CPTI(11b)),
136.07 (C7-Ph(1)), 136.80 (C9-Ph(1) 6-Ph), 148.09 (CPTI(6a)),
149.69 (CPTI(7)), 155.94 (CPTI(9)), 159.82 (CPTI(5)), 168.12
(CPTI(10a)).
5-Amino-7-phenyl-8,9,10,11-tetrahydroisoquinolino-
[3΄,4΄:4,5]thieno[2,3-b]quinoline 13-oxide (6c). The yield was
0.51 g (64%); m.p. 277—279 °C (DMF—MeOH). Found (%):
C, 72.41; H, 4.94; N, 10.42; S, 8.23. C24H19N3OS. Calculat-
ed (%): C, 72.52; H, 4.82; N, 10.57; S, 8.07. IR, ν/cm–1: 3468,
3308, 3357, 3211 (NH2), 3051, 2941, 1630, 1613, 1573, 1543, 1502,
1428, 1415, 1371, 1007 (S=O), 770, 699. 1H NMR (DMSO-d6),
δ: 1.60—1.73 (m, 2 H, 9-(CH2)THIQTQ); 1.80—1.92 (m, 2 H,
10-(CH2)THIQTQ); 2.41 (t, 2 H, 8-(CH2)THIQTQ, J = 5.9 Hz);
3.02 (t, 2 H, 11-(CH2)THIQTQ, J = 5.9 Hz); 6.80 (br.s, 2 H, NH2);
7.16—7,32 (m, 2 H, C(2)H7-Ph, C(6)H7-Ph); 7.42—7.52 (m, 3 H,
Substituted 5-aminopyrido[3΄,2΄:4,5]thieno[3,2-c]isoquino-
line-11,11-dioxides (8a—f) were obtained according to the pro-
cedure described for the synthesis of compounds 4a—f.
5-Amino-7,9-dimethylpyrido[3΄,2΄:4,5]thieno[3,2-c]isoquino-
line-11,11-dioxide (8a). The yield was 0.54 g (87%); m.p.
340—342 °C (DMF—MeOH). Found (%): C, 61.88; H, 4.16;
N, 13.50; S, 10.21. C16H13N3O2S. Calculated (%): C, 61.72; H, 4.21;
N, 13.50; S, 10.30. IR, ν/cm–1: 3472, 3416, 3376 (NH2), 2928,
1616, 1544, 1504, 1424, 1280 (SO2), 1152 (SO2), 1116, 752.
1H NMR (DMSO-d6), δ: 2.57 (s, 3 H, 7-Me); 2.91 (s, 3 H, 9-Me);
7.43 (s, 1 H, C(8)HPTI); 7.64 (t, 1 H, C(3)HPTI, J = 8.1 Hz);
7.86—7.93 (m, 2 H, C(1)HPTI, C(2)HPTI); 8.18 (s, 2 H, NH2);
8.41 (d, 1 H, C(4)HPTI, J = 8.8 Hz). 13C NMR (DMSO-d6), δ:
19.38 (7-Me), 23.56 (9-Me), 111.63 (CPTI(11a)), 115.77 (CPTI(4a)),
121.73 (CPTI(4)), 122.35 (CPTI(6b)), 125.69 (CPTI(3)), 127.43
(CPTI(1)), 129.84 (CPTI(11b)), 129.87 (CPTI(8)), 133.25 (CPTI(2)),
146.72 (CPTI(6a)), 147.05 (CPTI(7)), 157.56 (CPTI(10a)), 160.03
(CPTI(5)), 161.46 (CPTI(9)).
C(3)H7-Ph, C(4)H7-Ph, C(5)H7-Ph); 7.54 (t, 1 H, C(3)HTHIQTQ
J = 8.1 Hz); 7.79 (t, 1 H, C(2)HTHIQTQ, J = 8.1 Hz); 8.05 (d, 1 H,
C(1)HTHIQTQ, J = 8.1 Hz); 8.28 (d, 1 H, C(4)HTHIQTQ
,
,
J = 8.8 Hz). 13C NMR (DMSO-d6), δ: 21.90 (9-(CH2)THIQTQ),
21.98 (10-(CH2)THIQTQ), 27.07 (8-(CH2)THIQTQ), 32.63
(11-(CH2)THIQTQ), 116.05 (CTHIQTQ(4a)), 119.63 (CTHIQTQ(13a)),
122.36 (CTHIQTQ(4)), 125.33 (CTHIQTQ(3)), 125.81 (CTHIQTQ(6b)),
126.68 (CTHIQTQ(1)), 127.77 (d, C7-Ph(3), C7-Ph(5), J = 5.5 Hz),
127.81 (C7-Ph(2), C7-Ph(6)), 128.34 (d, C4-Ph(4), J = 22.1 Hz),
132.22 (CTHIQTQ(2)), 133.66 (CTHIQTQ(13b)), 133.90 (C7-Ph(1)),
135.16 (CTHIQTQ(7a)), 146.67 (CTHIQTQ(6a)), 149.98
(CTHIQTQ(7)), 158.09 (CTHIQTQ(5)), 159.61 (CTHIQTQ(11a)),
163.65 (CTHIQTQ(12a)).
5-Amino-8,9,10,11-tetrahydroisoquinolino[3΄,4΄:4,5]thieno-
[2,3-b]quinoline 13,13-dioxide (8b). The yield was 0.42 g (62%);
m.p. 322—324 °C (DMF—MeOH). Found (%): C, 64.31;
H, 4.39; N, 12.33; S, 9.61. C18H15N3O2S. Calculated (%):
C, 64.08; H, 4.48; N, 12.45; S, 9.90. IR, ν/cm–1: 3456, 3408,
3320, 3248 (NH2), 3216, 2952, 1640, 1624, 1616, 1584, 1564,
1544, 1512, 1432, 1384, 1292 (SO2), 1136 (SO2), 1024, 768.
1H NMR (DMSO-d6), δ: 1.70—1.80 (m, 2 H, 9-(CH2)THIQTQ);
1.82—1.92 (m, 2 H, 10-(CH2)THIQTQ); 2.86—3.00 (m, 4 H,
5-Amino-9-methyl-7-phenylpyrido[3΄,2΄:4,5]thieno[3,2-c]-
isoquinoline 11-oxide (6d). The yield was 0.25 g (35%); m.p.
252—256 °C (DMF—MeOH). Found (%): C, 70.41; H, 4.31;
N, 11.60; S, 9.03. C21H15N3OS. Calculated (%): C, 70.57; H, 4.23;
N, 11.76; S, 8.97. IR, ν/cm–1: 3434, 3322, 3288, 3204 (NH2),
3056, 1618, 1589, 1544, 1501, 1419, 1009 (S=O), 761, 696, 683.
1H NMR (DMSO-d6), δ: 2.65 (s, 3 H, 9-Me); 7.31 (br.s, 2 H,
NH2); 7.43 (s, 1 H, C(8)HPTI); 7.49—7.52 (m, 3 H, C(3)H7-Ph
,
8-(CH2)THIQTQ, 11-(CH2)THIQTQ); 7.65 (t, 1 H, C(3)HTHIQTQ,
C(4)H7-Ph, C(5)H7-Ph); 7.57 (t, 1 H, C(3)HPTI, J = 7.3 Hz);
7.63—7.67 (m, 2 H, C(2)H7-Ph,C(6)H7-Ph); 7.82 (t, 1 H,
C(2)HPTI, J = 7.3 Hz); 8.07 (d, 1 H, C(1)HPTI, J = 7.9 Hz);
8.35 (d, 1 H, C(4)HPTI, J = 8.5 Hz). 13C NMR (DMSO-d6),
J = 8.1 Hz); 7.87—7.93 (m, 2 H, C(1)HTHIQTQ, C(2)HTHIQTQ);
7.96 (s, 1 H, C(8)HTHIQTQ); 8.25 (br.s, 2 H, NH2); 8.44 (d, 1 H,
C(4)HTHIQTQ, J = 8.8 Hz). 13C NMR (DMSO-d6), δ: 21.75
(9-(CH2)THIQTQ), 22.21 (10-(CH2)THIQTQ), 28.79 (8-(CH2)THIQTQ),

910
Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
Kalugin et al.
32.26 (11-(CH2)THIQTQ), 112.49 (CTHIQTQ(13a)), 116.75
(CTHIQTQ(4a)), 121.74 (CTHIQTQ(4)), 124.94 (CTHIQTQ(6b)),
125.84 (CTHIQTQ(3)), 127.53 (CTHIQTQ(1)), 129.83 (CTHIQTQ(13b)),
130.51 (CTHIQTQ(7)), 133.36 (CTHIQTQ(2)), 137.81 (CTHIQTQ(7a)),
144.80 (CTHIQTQ(6a)), 154.81 (CTHIQTQ(12a)), 160.12 (CTHIQTQ(5)),
162.01 (CTHIQTQ(11a)).
C(4)HPTI, J = 8.1 Hz). 13C NMR (DMSO-d6), δ: 112.47
(CPTI(11a)), 116.34 (CPTI(4a)), 122.00 (CPTI(4)), 122.36
(CPTI(6b)), 124.82 (CPTI(8)), 125.73 (CPTI(3)), 126.32 (C6-Ph(4)),
127.30 (C9-Ph(3), C9-Ph(5)), 127.76 (CPTI(1)), 127.82 (C7-Ph(3),
C7-Ph(5)), 129.31 (C7-Ph(2), C7-Ph(6)), 129.79 (CPTI(11b)),
130.19 (C9-Ph(2), C9-Ph(6)), 130.68 (C9-Ph(4)), 133.32 (CPTI(2)),
136.28 (C7-Ph(1)), 136.44 (C9-Ph(1)), 145.80 (CPTI(7)), 148.79
(CPTI(6a)), 157.36 (CPTI(9)), 159.09 (CPTI(10a)), 160.70
(CPTI(5)).
5-Amino-7-phenyl-8,9,10,11-tetrahydroisoquinolino-
[3΄,4΄:4,5]thieno[2,3-b]quinoline 13,13-dioxide (8c). The yield
was 0.40 g (48%); m.p. 287—290 °C (DMF—MeOH). Found (%):
C, 69.85; H, 4.57; N, 10.09; S, 7.83. C24H19N3O2S. Calculat-
ed (%): C, 69.71; H, 4.63; N, 10.16; S, 7.75. IR, ν/cm–1: 3461,
3342, 3236 (NH2), 3058, 2934, 1634, 1614, 1582, 1547, 1505,
1429, 1373, 1279 (SO2), 1142, 1129 (SO2), 764, 758, 695. 1H NMR
(DMSO-d6), δ: 1.62—1.75 (m, 2 H, 9-(CH2)THIQTQ); 1.80—1.90
5-Amino-9-(4-methoxyphenyl)-7-(trifluoromethyl)pyrido-
[3΄,2΄:4,5]thieno[3,2-c]isoquinoline 11,11-dioxide (8f). The yield
was 0.58 g (63%), m.p. 323—325 °C (CHCl3—MeOH). Found (%):
C, 57.63; H, 3.13; N, 9.26; S, 7.08. C22H14F3N3O3S. Calculat-
ed (%): C, 57.77; H, 3.08; N, 9.19; S, 7.01. IR, ν/cm–1: 3488,
3392, 3376, 3352, 3232 (NH2), 1640, 1616, 1600, 1552, 1416,
1368, 1296 (SO2), 1256, 1144 (SO2), 760. 1H NMR (DMSO-d6),
(m, 2 H, 10-(CH2)THIQTQ); 2.42 (t, 2 H, 8-(CH2)THIQTQ
,
J = 5.9 Hz); 3.04 (t, 2 H, 11-(CH2)THIQTQ, J = 5.9 Hz); 7.02
(br.s, 2 H, NH2); 7.23—7.32 (m, 2 H, C(2)H7-Ph,C(6)H7-Ph);
7.46—7.53 (m, 3 H, C(3)H7-Ph, C(4)H7-Ph, C(5)H7-Ph); 7.60
(t, 1 H, HTHIQTQ(3), J = 7.3 Hz); 7.82—7.97 (m, 2 H, HTHIQTQ(1),
HTHIQTQ(2)); 8.34 (d, 1 H, HTHIQTQ(4), J = 8.8 Hz). 13C NMR
(DMSO-d6), δ: 21.68 (9-(CH2)THIQTQ), 21.77 (10-(CH2)THIQTQ),
27.26 (8-(CH2)THIQTQ), 32.63 (11-(CH2)THIQTQ), 112.45
(CTHIQTQ(13a)), 115.61 (CTHIQTQ(4a)), 121.52 (CTHIQTQ(4)),
121.61 (CTHIQTQ(6b)), 125.48 (CTHIQTQ(3)), 127.20 (CTHIQTQ(1)),
127.87 (C7-Ph(3), C7-Ph(5)), 127.93 (C7-Ph(4)), 128.11 (C7-Ph(2),
C7-Ph(6)), 129.56 (CTHIQTQ(13b)), 132.82 (CTHIQTQ(2)), 135.18
(C7-Ph(1)), 135.81 (CTHIQTQ(7a)), 145.75 (CTHIQTQ(7)), 146.81
(CTHIQTQ(6a)), 154.96 (CTHIQTQ(12a)), 159.35 (CTHIQTQ(5)),
160.17 (CTHIQTQ(11a)).
δ: 3.86 (s, 3 H, OMe); 7.14 (d, 2 H, C(3)H9-Ph, C(5)H9-Ph
,
J = 8.8 Hz); 7.72 (t, 1 H, C(3)HPTI, J = 7.3 Hz); 7.90—8.03
(m, 2 H, C(1)HPTI, C(2)HPTI); 8.21 (br.s, 2 H, NH2); 8.27 (d, 2 H,
C(2)H9-Ph, C(6)H9-Ph, J = 8.1 Hz); 8.42 (s, 1 H, C(8)HPTI);
8.50 (d, 1 H, C(4)HPTI, J = 7.3 Hz). 13C NMR (DMSO-d6), δ:
55.65 (OМe), 113.06 (CPTI(11a)), 114.86 (C9-Ph(3), C9-Ph(5)),
116,41 (CPTI(4a)), 119.82 (q, CPTI(8), J = 6.0 Hz), 121.70
(CPTI(6b)), 122.60 (CPTI(4)), 123.97 (q, CF3, JCF = 275.4 Hz),
125.80 (CPTI(3)), 128.00 (C9-Ph(1)), 128.46 (CPTI(1)), 129.30
(C9-Ph(2), C9-Ph(6)), 129.52 (CPTI(11b)), 133.55 (CPTI(2)),
134.20 (q, CPTI(7),
J = 33.2 Hz), 143.39 (CPTI(6a)),
159.01 (CPTI(9)), 159.64 (CPTI(10a)), 161.42 (CPTI(5)), 162.07
(C9-Ph(4)).
5-Amino-9-methyl-7-phenylpyrido[3΄,2΄:4,5]thieno[3,2-c]-
isoquinoline 11,11-dioxide (8d). The yield was 0.39 g (52%);
m.p. 266—268 °C (DMF—MeOH). Found (%):C, 67.71; H, 4.11;
N, 11.18; S, 8.68. C21H15N3O2S. Calculated (%): C, 67.54;
H, 4.05; N, 11.25; S, 8.59. IR, ν/cm–1: 3479, 3379, 3226
(NH2), 1625, 1595, 1544, 1501, 1420, 1284 (SO2), 1148, 1132
(SO2), 1071, 764. 1H NMR (DMSO-d6), δ: 2.66 (s, 3 H, 9-Мe);
References
1. C. Szabo, V. L. Dawson, Trends Pharmacol. Sci., 1998,
19, 287.aaaaa
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. Na-
gafuji, M. Cushman, J. Med. Chem., 1999, 42, 446.
4. M. Cushman, M. Jayaraman, J. A. Vroman, A. K. Fukunaga,
B. M. Fox, G. Kohlhagen, D. Strumbergt, Y. Pommier,
J. Med. Chem., 2000, 43, 3688.
5. V. E. Kalugin, A. M. Shestopalov, Tetrahedron Lett., 2011,
52, 1557.
7.46—7.54 (m, 4 H, C(8)HPTI and C(3)H7-Ph, C(4)H7-Ph
C(5)H7-Ph); 7.57 (br.s, 2 H, NH2); 7.63 (t, 1 H, C(3)HPTI
,
,
J = 7.3 Hz); 7.70—7.78 (m, 2 H, C(2)H7-Ph, C(6)H7-Ph);
7.89 (t, 1 H, C(2)HPTI, J = 8.1 Hz); 7.95 (d, 1 H, C(1)HPTI
,
J = 8.1 Hz); 8.40 (d, 1 H, C(4)HPTI, J = 8.1 Hz). 13C NMR
(DMSO-d6), δ: 23.42 (6-Me), 111.65 (CPTI(11a)), 116.02
(CPTI(4a)), 121.10 (CPTI(6b)), 121.66 (CPTI(4)), 125.53
(CPTI(3)), 127.35 (CPTI(1)), 127.58 (C7-Ph(3), C7-Ph(5)), 128.97
(C7-Ph(4)), 129.45 (CPTI(8)), 129.62 (CPTI(11b)), 129.79
(C7-Ph(2), C7-Ph(6)), 132.95 (CPTI(2)), 136.09 (C7-Ph(1)), 145.78
(CPTI(7)), 147.56 (CPTI(6a)), 158.19 (CPTI(10a)), 160.22
(CPTI(5)), 160.44 (CPTI(9)).
6. V. E. Kalugin, A. M. Shestopalov, Russ. Chem. Bull. (Int. Ed.),
2014, 63, 2478.
7. V. E. Kalugin, A. M. Shestopalov, Russ. Chem. Bull. (Int. Ed.),
2014, 63, 426.
5-Amino-7,9-diphenylpyrido[3΄,2΄:4,5]thieno[3,2-c]isoquino-
line 11,11-dioxide (8e). The yield was 0.63 g (73%); m.p. 336—338 °C
(DMF—MeOH). Found (%): C, 71.61; H, 4.04; N, 9.76; S, 7.25.
C26H17N3O2S. Calculated (%): C, 71.71; H, 3.95; N, 9.65; S, 7.36.
IR, ν/cm–1: 3472, 3432, 3376 (NH2), 1616, 1600, 1592, 1584,
1576, 1544, 1424, 1284 (SO2), 1132 (SO2), 760. 1H NMR
8. V. E. Kalugin, A. M. Shestopalov, Russ. Chem. Bull. (Int. Ed.),
2017, 66, 523.
9. V. E. Kalugin, A. M. Shestopalov, Russ. Chem. Bull. (Int. Ed.),
2015, 64, 878.
10. K. Gewald, M. Hentschel, U. Illgen, J. Pract. Chem., 1974,
316, 1030.
11. L. A. Rodinovskaya, E. V. Belukhina, A. M. Shesto-
palov, V. P. Litvinov, Russ. Chem. Bull. (Int. Ed.), 1994,
43, 489.
(DMSO-d6), δ: 7.45—7.60 (m, 6 H, C(3)H9-Ph, C(4)H9-Ph
,
C(5)H9-Ph and C(3)H7-Ph, C(4)H7-Ph, C(5)H7-Ph); 7.65 (t, 1 H,
C(3)HPTI, J = 8.1 Hz); 7.68 (br.s, 2 H, NH2); 7.70—7.78 (m, 2 H,
C(2)H7-Ph, C(6)H7-Ph); 7.93 (t, 1 H, C(2)HPTI, J = 7.3 Hz); 8.00
(d, 1 H, C(1)HPTI, J = 8.1 Hz); 8.12 (s, 1 H, C(8)HPTI);
8.22—8.30 (m, 2 H, C(2)H9-Ph, C(6)H9-Ph); 8.43 (d, 1 H,
12. Yu. A. Sharanin, V. P. Litvinov, A. M. Shestopalov, V. N.
Nesterov, V. K. Struchkov, Bull. Acad. Sci. USSR, Div. Chem.
Sci. (Engl. Transl.), 1985, 34, 1619.

5-Aminopyrido[3´,2´:4,5]thieno[3,2-c]isoquinolines Russ. Chem. Bull., Int. Ed., Vol. 67, No. 5, May, 2018
911
13. V. P. Litvinov, V. K. Promonenkov, Yu. A. Sharanin, A. M.
Shestopalov, L. A. Rodinovskaya, V. N. Nesterov, V. K.
Struchkov, Bull. Acad. Sci. USSR, Div. Chem. Sci.
(Engl. Transl.), 1985, 34, 1940.
Yang, Y.-Q. Wei, L.-T. Yu, Bioorg. Med. Chem. Lett., 2014,
24, 1581.
16. T. Mukayama, H. Tanaka, Bull. Chem. Soc. Jpn, 1956,
29, 908.aa
14. A. A. Krause, E. A. Bomika, A. M. Shestopalov, L. A.
Rodinovskaya, Yu. E. Pelcher, G. Ya. Dubur, Yu. A. Shara-
nin, V. K. Promonenkov, Chem. Heterocycl. Compd.
(Engl. Transl.), 1981, 17, 279.
15. N.-Y. Wang, W.-Q. Zuo, Y. Xu, C. Gao, X.-X. Zeng,
L.-D. Zhang, X.-Y. You, C.-T. Peng, Y. Shen, S.-Y.
Received June 23, 2017;
in revised form December 5, 2017;
accepted December 28, 2017