Utilization of potassium carbonate for the synthesis of 2-(organylsulfonyl)thieno[2,3-b]pyridine derivatives

Article abstract of DOI:10.1007/s11172-019-2393-7

A novel preparative method for the synthesis of 2-(organylsulfonyl)thieno[2,3-b]pyridine derivatives has been developed, which allows one to obtain the desired products in a good yield and to shorten the reaction duration. The reaction of 3-cyanopyridine-

Full text of DOI:10.1007/s11172-019-2393-7

Russian Chemical Bulletin, International Edition, Vol. 68, No. 2, pp. 357—364, February, 2019
357
Utilization of potassium carbonate for the synthesis of
2
-(organylsulfonyl)thieno[2,3-b]pyridine derivatives*
V. E. Kalugin and A. M. Shestopalov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. E-mail: vek@ioc.ac.ru
A novel preparative method for the synthesis of 2-(organylsulfonyl)thieno[2,3-b]pyridine
derivatives has been developed, which allows one to obtain the desired products in a good yield
and to shorten the reaction duration. The reaction of 3-cyanopyridine-2(1H)-thiones with
chloromethyl organyl sulfones in the presence of potassium carbonate as the base gave 2-(organ-
ylsulfonyl)thieno[2,3-b]pyridine-3-amines. The same reaction of methyl 4,6-dimethylpyridine-
2
(1H)-thione-3-carboxylate with chloromethyl organyl sulfones resulted in tautomeric mixtures
of 4,6-dimethyl-2-(organylsulfonyl)thieno[2,3-b]pyridine-3-oles and 4,6-dimethyl-2-(organyl-
sulfonyl)thieno[2,3-b]pyridine-3(2H)-ones.
Key words: 3-cyanopyridine-2(1H)-thiones, methyl 4,6-dimethylpyridine-2(1H)-thione-
3
-carboxylate, chloromethyl organyl sulfones, potassium carbonate, 2-(organylsulfonyl)-
thieno[2,3-b]pyridine-3-amines, 4,6-dimethyl-2-(organylsulfonyl)thieno[2,3-b]pyridine-3-oles,
,6-dimethyl-2-(organylsulfonyl)thieno[2,3-b]pyridine-3(2H)-ones.
4
Derivatives of 2-(organylsulfonyl)thieno[2,3-b]pyrid-
ines are of interest as pharmacological agents. In particu-
lar, 3-aryl-2-(organylsulfonyl)thieno[2,3-b]pyridines have
demonstrated an activity towards the glutamate receptors
mGluRl and mGluR5 and can thus be utilized for the
treatment of a wide range of neurological and mental
diseases.1
ratio of reagents 1 : 2 : K CO equal to 1 : 1 : 1.4 at
2 3
70—75 C for 40—50 min (Scheme 1). The yields of com-
pounds 3a—x are given in Table 1.
Scheme 1
,2
We have previously obtained the first representatives
of this class of compounds, 2-(organylsulfonyl)thieno-
[
2,3-b]pyridine-3-amines, via the reaction of substituted
3
-cyanopyridine-2-thiones and chloromethyl organyl
sulfones in DMF in the presence of triethylamine as the
base. This reaction at 100—110 C is usually completed
3
within 7 h. The drawback of that method is the long reac-
tion duration. At this end, we have selected anhydrous
potassium carbonate as the base.
Results and Discussion
Reagents and conditions: K CO , DMF, 70—75 C, 50 min.
2
3
In the present work, we have utilized 3-cyanopyridin-
1
R´
R″
R‴
2
(1H)-thiones 1a—g bearing alkyl, aryl, trifluoromethyl,
R″R'''
amide, acetyl, and ester groups and chloromethyl organyl
sulfones 2a—c, wherein the organyl group is phenyl,
benzyl, and butyl ones, and also chloromethylsulfonamides
a
b
c
d
e
f
Me
H
Ph
CF3
Ph
H
H
Me
(CH2)4
H
H
Ph
Ph
Me
Me
Me
2
d,e. The reaction was carried out in DMF at a molar
C(O)NHPh
Ac
g
Ph
CO Et
2
*
Dedicated to Corresponding Member of the Russian Academy
of Sciences G. I. Nikishin on the occasion of his 90th birthday.
2: R = Ph (a), Bn (b), Bu (c), morpholin-4-yl (d), NHPh (e)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0357—0364, February, 2019.
066-5285/19/6802-0357 © 2019 Springer Science+Business Media, Inc.
1

3
58
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Kalugin and Shestopalov
Table 1. Yields of compounds 3a—x
proceeding along with the formation of thienopyridines 3 in
the case of sulfones 2b and 2c. Thus, the interaction of pyr-
idinethione 1 with sulfone 2b in addition to target products
Product
R
R´
R´´
H
R´´´
Me
Yield
(%)
R″R'''
3
h—m provided some amounts of styrene 4, which was
formed via the Ramberg—Bäcklund reaction (Scheme 2).
We have also explored the opportunity to obtain
thieno[2,3-b]pyridines 3 using chloromethylsulfonamides
2d,e as the starting compounds, which can be easily pre-
pared via the reaction of chloromethylsulfonyl chloride
with amines. The reaction was carried out under the same
conditions as in the case of sulfones 2a—c (see Scheme 1).
It was found that desired products 3u—x were also pro-
duced in this case, but in the yields lower than that for
sulfones 2a—c (see Table 1).
It was interesting to investigate the synthetic opportu-
nity for 2-(organylsulfonyl)thieno[2,3-b]pyridine deriva-
tives using methyl 4,6-dimethylpyridine-2(1H)-thione-3-
carboxylate 5 as the starting compound containing the
ester group at position 3. Such studies have not been pre-
viously conducted. The reaction of compound 5 with
sulfones 2a—e was carried out under similar conditions as
described above, except that the reaction products were
isolated after the acidification of reaction mixture with
acetic acid (Scheme 3).
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bn
Bn
Bn
Bn
Bn
Bn
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Me
H
Ph
78
70
74
69
47
70
55
55
72
57
31
43
41
74
71
64
57
68
58
52
46
44
36
32
(CH2)4
H
H
Ph
Ph
Me
Me
Me
Me
CF3
Ph C(O)NHPh
H
Ph
Me
H
Ph
CF3
Ac
CO Et
2
H
(CH2)4
H
H
Ph
Ph
Me
Me
Me
Ph C(O)NHPh
H
Me
H
Ph
CF3
Ac
H
(CH2)
4
H
H
Ph
Ph
Me
Me
Me
Me
Ph
Ph C(O)NHPh
H
Ph
s
t
u
v
w
x
Ac
CO Et
2
Morpholin-4-yl Me
Morpholin-4-yl Ph
H
H
H
H
NHPh
NHPh
Me
Ph
Me
Ph
It was found that the products in the reaction of pyri-
dinethione 5 with sulfones 2a—e were mixtures of tauto-
meric compounds: 4,6-dimethyl-2-(organylsulfonyl)thi-
eno[2,3-b]pyridine-3-oles 6a—e and 4,6-dimethyl-2-
(organylsulfonyl)thieno[2,3-b]pyridine-3(2H)-ones 7a—e
(Table 2). This fact was confirmed by the presence of
absorption bands at 3396—3320 cm– for the hydroxyl
As one can see from Table 1, the yield of desired prod-
ucts 3 depends on the structure of pyridinethione 1 and,
especially, on that of sulfone 2. Thus, the highest yields
of the target products were observed for reactions with
chloromethyl phenyl sulfone (2a, R = Ph), while the low-
est ones were in the case of chloromethyl benzyl sulfone
1
–
1
group of compounds 6a—e and at 1708—1704 cm for
the carbonyl group of compounds 7a—e in the IR spectra
1
of reaction products. H NMR spectra of the reac-
(
2b, R = Bn). The yields of the desired products for reac-
tion products contain proton signals in the region of
 = 8.9—9.5 from the hydroxyl group of compounds 6a—e
and  = 5.1—5.2 from the H(2) atom at the thieno[2,3-b]-
tions with chloromethyl butyl sulfone (2c, R = Bu) were
intermediate. This can be explained by side reactions
Scheme 2
Scheme 3
Reagents and conditions: K CO , DMF, 70—75 C, 50 min.
2
3

2
-(Organylsulfonyl)thieno[2,3-b]pyridines
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
359
Table 2. Yields of the products and tautomeric ratios in the reac-
tion of compound 5 with chloromethyl organyl sulfones 2a—e
In this case, a quite rare phenomenon was observed
since the cation nature affected not only the reaction rate,
but also the reaction possibility.
Products
R
Yield (%)
Ratio of
tautomers 6 : 7*
Therefore, we have developed the convenient prepara-
tive method for the synthesis of substituted 2-(organylsul-
fonyl)thieno[2,3-b]pyridine-3-amines via an utilization
of potassium carbonate as the base, which allowed us to
significantly shorten the reaction time and to obtain the
desired products in fairly good yields. It was found that
pyridine-2(1H)-thione bearing an ester group at the posi-
tion 3 can also react with chloromethyl organyl sulfones
giving the mixture of tautomers, 2-(organylsulfonyl)-
thieno[2,3-b]pyridine-3-oles and 2-(organylsulfonyl)thi-
eno[2,3-b]pyridine-3(2H)-ones.
6
6
6
6
6
a + 7a
b + 7b
c + 7c
d + 7d
e + 7e
Ph
Bn
51
41
46
42
48
80 : 20
68 : 32
83 : 17
90 : 10
40 : 60
Bu
Morpholin-4-yl
NHPh
*
According to the NMR data.
pyridine cycle of compounds 7a—e. 13C NMR spectra of
tautomers 6a—e contain signals of carbon atoms in the
range of  = 105.70—112.24 from the C(2) atom of
thieno[2,3-b]pyridine cycle and = 145.80—146.17 from
the carbon atom bearing the OH group, while those of
tautomers 7a—e contain the signals in the interval of
Experimental
All values of melting points were measured on a Kofler plate.
IR spectra were recorded on a Specord M82 spectrometer in KBr
1
13
pellets. H (300 MHz) and C (75 MHz) NMR spectra were
recorded on a Bruker Avance-300 spectrometer in DMSO-d or

= 69.21—70.28 from the C(2) atom of thieno[2,3-b]-
6
pyridine cycle and  = 189.14—190.67 from the carbonyl
group. As one can see from Table 2, the major product is
tautomer 6 in most reactions, and only in the case of
product in the reaction of pyridinethione 5 with sulfone
CDCl using SiMe as an internal standard. Elemental analysis
3
4
was carried out using a Perkin-Elmer 2400 CHN analyzer.
A chromatographic column loaded with silica gel (60—80 mesh)
was used for the isolation of reaction products.
2
e, tautomer 7e is the major one.
Synthesis of the starting compounds. 3-Cyanopyridine-2(1H)-
4
5
6
7
8
9
10
It was interesting to compare our method for the
thiones (1a) , (1b) , (1c) , (1d) , (1e) , (1f) , (1g) and sulfones
3
preparation of 2-(organylsulfonyl)thieno[2,3-b]pyridine
derivatives with that reported previously in the patent,
(2a—c) were prepared according to the known procedures.
1
Synthesis of chloromethylsulfonamides 2d,e (general proce-
dure). A solution of amine (40 mmol) in CHCl (20 mL) was
wherein 2-(arylsulfonyl)thieno[2,3-b]pyridine-3-amines
were obtained in the yields of 60—80% via the reaction of
3
added at 0—5 C to a solution of chloromethylsulfonyl chloride
(
3 g, 20 mmol) in CHCl (20 mL). The reaction mixture was
3
3
-cyanopyridine-2-thione with chloromethyl aryl sulfones
stirred at that temperature for 20 min, warmed to room tem-
perature, and stirred for 1 h. It was then washed with water
in DMF in the presence of sodium methoxide as the base
at 120 C for 2 h. However, in our case, the reaction of
(
2×30 mL) and dried over MgSO , the solvent was evaporated,
4
3
-cyanopyridine-2(1H)-thione 1a with chloromethyl
and the product was recrystallized from CHCl —hexane mixture.
3
organyl sulfones 2a,b in the presence of sodium methoxide
4-(Chloromethylsulfonyl)morpholine (2d). The yield was 3.11 g
under those conditions gave mixtures of starting sulfones
2
(78%), colorless crystals, m.p. 69—71 C (cf. Ref. 11: 70.5—71 C
–
1
(
1
EtOH)). IR, /cm : 3016, 2976, 2844, 1456, 1348 (SO ), 1264,
a,b and alkylation products 8a,b (Scheme 4).
2
1
160 (SO ), 1104, 956, 748. H NMR (CDCl ),: 3.48 (t, 4 H,
2
3
CH NCH , J = 4.4 Hz); 3.77 (t, 4 H, CH OCH , J = 4.4 Hz);
2
2
2
2
Scheme 4
4.55 (s, 2 H, CH2Cl).
-Chloro-N-phenylmethanesulfonamide (2e). The yield was
.36 g (82%), colorless crystals, m.p. 76—78 C (cf. Ref. 12:
1
3
7
–
1
5—78 C (CCl )). IR, /cm : 3272 (NH), 3004, 2948, 1596,
4
1
6
1
486, 1476, 1412, 1364 (SO ), 1164 (SO ), 1120, 936, 756, 728,
2 2
1
92. H NMR (CDCl ), : 4.50 (s, 2 H, CH Cl); 7.02 (br.s,
3
2
H, NH); 7.24—7.35 (m, 3 H, HPh(2), HPh(4), HPh(6)); 7.37—7.46
(
m, 2 H, HPh(3), HPh(5)).
Synthesis of substituted 2-(organylsulfonyl)thieno[2,3-b]-
pyridines 3a—x (general procedure). Anhydrous K CO (0.77 g,
2
3
5
1
.6 mmol) was added at 50 C to a solution of pyridinethione
a—g (4 mmol) and sulfone 2a—e (4 mmol) in DMF (7 mL).
The reaction mixture was stirred at 70—75 C for 50 min, cooled
to room temperature, and poured into H O (30 mL). The prod-
2
uct was extracted with CHCl (3×15 mL). The extract was washed
3
with H O (3×20 mL) and dried over MgSO , the solvent was
2
4
evaporated, and the product was purified by chromatography on
silica gel. The eluent was CHCl —hexane mixture (3 : 2, 2 : 1,
Reagents and conditions: MeONa, DMF, 120—125 C, 2 h.
3

3
60
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Kalugin and Shestopalov
and 3 : 1). After the evaporation of eluate, the substance was
recrystallized from an appropriate solvent. During the chromato-
graphic separation of products of the reaction of pyridinethiones 1
and chloromethyl benzyl sulfone 2b, styrene 4 was found in one of
the fractions, whose structure was confirmed by NMR spectroscopy.
C, 55.29; H, 3.02; N, 6.45; S, 14.76. IR, /cm–1: 3520, 3392
(NH ), 1632, 1516, 1368, 1304, 1296 (SO ), 1260, 1172, 1140
2
2
1
(SO ), 1088, 776, 724, 688. H NMR (DMSO-d ),: 6.12 (s, 2 H,
2
6
NH ); 7.53—7.58 (m, 3 H, H
(3), HPhSO2(4), HPhSO2(5));
PhSO
2
2
7.61—7.77 (m, 3 H, H6-Ph(3), H6-Ph(4), H6-Ph(5)); 8.04 (d, 2 H,
4
,6-Dimethyl-2-(phenylsulfonyl)thieno[2,3-b]pyridine-3-amine
3a). The yield was 1 g (78%), yellow crystals, m.p. 197—199 C
CHCl —MeOH) (cf. Ref. 3: m.p. 197—199 C (MeOH)).
HPhSO2(2), HPhSO2(6), J = 7.3 Hz); 8.20—8.27 (m, 2 H, H6-Ph(2),
13
H6-Ph(6)); 8.32 (s, 1 H, HTP(5)). C NMR (DMSO-d ), :
6
104.37 (CTP(2)); 114.42 (q, CTP(5), J = 6.6 Hz); 119.14 (q, CF3,
JC,F = 223.4 Hz); 124.22 (CTP(3a)); 126.35 (CPhSO2(3), CPhSO2(5));
127.38 (C6-Ph(3), C6-Ph(5)); 128.91 (C6-Ph(2), C6-Ph(6)); 129.83
3
1
5
14
2
2
2
1
–
Calculated (%): C, 56.58; H, 4.43; N, 8.80; S, 20.14. IR, /cm
:
(
CPhSO2(2), CPhSO2(6)); 130.79 (C6-Ph(4)); 132.94 (q, CTP(4),
J = 33.2 Hz); 134.02 (CPhSO2(4)); 135.86 (C6-Ph(1)); 140.56
CPhSO2(1)); 142.02 (CTP(3)); 157.36 (CTP(6)); 161.82 (CTP(7a)).
3
500, 3384 (NH ), 2916, 1620, 1580, 1552, 1508, 1444, 1300
2
1
SO ), 1148 (SO ), 1012, 688. H NMR (DMSO-d ), : 2.55
2
2
6
(
s, 3 H, 4-CH ); 2.70 (s, 3 H, 6-CH ); 5.40 (s, 2 H, NH ); 6.85
3
3
2
6
-Methyl-4-phenyl-5-(phenylaminocarbonyl)-2-(phenylsulf-
onyl)thieno[2,3-b]pyridine-3-amine (3e). The yield was 0.94 g
47%), light yellow crystals, m.p. 293—295 C (CHCl —MeOH).
s, 1 H, HTP(5));* 7.40—7.70 (m, 3 H, HPhSO2(3), H
(4),
PhSO
2
1
3
HPhSO2(5)); 7.92—8.07 (m, 2 H, HPhSO2(2), HPhSO2(6)). C NMR
(
DMSO-d ), : 19.87 (4-CH ); 23.78 (6-CH ); 100.95 (CTP(2));
3
6
3
3
Found (%): C, 65.04; H, 4.13; N, 8.35; S, 12.72. C H N O S .
1
1
22.39 (CTP(3a)); 122.49 (CTP(5)); 126.04 (CPhSO2(3), CPhSO2(5));
29.63 (CPhSO2(2), CPhSO2(6)); 133.43 (CPhSO2(4)); 142.02
CPhSO2(1)); 146.00 (CTP(3)); 146.29 (CTP(4)); 159.87 (CTP(6));
27 21
3
3 2
Calculated (%): C, 64.91; H, 4.24; N, 8.41; S, 12.83. IR,
–
1

/cm : 3492, 3388 (NH ), 3324 (CONH), 3056, 1676 (C=O),
2
1
608, 1596, 1544, 1444, 1316, 1288 (SO ), 1144 (SO ), 760, 688.
160.11 (CTP(7a)).
2
2
1
H NMR (DMSO-d ),: 2.63 (s, 3 H, 6-CH ); 5.23 (s, 2 H,
2
-(Phenylsulfonyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-
6
3
NH ); 7.04 (t, 1 H, HPhN(4), J = 7.3 Hz); 7.23 (t, 2 H, HPhN(3),
HPhN(5), J = 7.3 Hz); 7.28 (d, 2 H, HPhN(2), HPhN(6), J = 7.3 Hz);
-amine (3b). The yield was 0.93 g (70%), yellow crystals, m.p.
2
3
7
.40—7.52 (m, 5 H, 4-Ph); 7.55—7.68 (m, 3 H, HPhSO2(3),
17
16
2
2 2
–
1
HPhSO2(4), HPhSO2(5)); 7.93 (d, 2 H, H
(2), HPhSO2(6),
PhSO
2
2
1
3
1
J = 7.3 Hz); 10.33 (s, 1 H, NHCO). C NMR (DMSO-d ), :
6
2
2
2
2.42 (6-CH ); 101.60 (CTP(2)); 119.60 (CPhN(2), CPhN(6));
3
6
1
23.97 (CPhN(4)); 126.06 (CPhSO2(3), CPhSO2(5)); 126.12 (CTP(3a));
28.45 (C4-Ph(3), C4-Ph(5)); 128.54 (C4-Ph(2), C4-Ph(6)); 128.62
CPhN(3), CPhN(5)); 129.44 (C4-Ph(4)); 129.56 (CPhSO2(2),
CPhSO2(6)); 130.83 (CTP(5)); 132.58 (CPhN(1)); 133.51 (CPhSO2(4));
,
1
(
(3),
2
PhSO
2
(2), HPhSO2(6),
PhSO
2
13
6
1
(
38.03 (C4-Ph(1)); 141.62 (CPhSO2(1)); 144.19 (CTP(3)); 144.23
CTP(4)); 155.95 (CTP(6)); 159.51 (CTP(7a)); 164.29 (C=O).
-Acetyl-6-methyl-2-(phenylsulfonyl)thieno[2,3-b]pyridine-
-amine (3f). The yield was 0.97 g (70%), yellow crystals, m.p.
2
3
2.10 (6-CH2THTQ); 22.26 (7-CH2THTQ); 28.27 (5-CH2THTQ);
2.46 (8-CH2THTQ); 98.64 (CTHTQ(2)); 123.98 (CTHTQ(3a));
5
1
25.96 (CPhSO2(3), CPhSO2(5)); 129.00 (CTHTQ(4a)); 129.48
PhSO2(2), CPhSO2(6)); 131.91 (CTHTQ(4)); 133.19 (CPhSO2(4));
42.40 (CPhSO2(1)); 144.58 (CTHTQ(3)); 156.79 (CTHTQ(9a));
60.04 (CTHTQ(8a)).
,6-Diphenyl-2-(phenylsulfonyl)thieno[2,3-b]pyridine-3-amine
3c). The yield was 1.31 g (74%), yellow crystals, m.p. 213—216 C
CHCl —MeOH). Found (%): C, 67.61; H, 4.01; N, 6.28;
3
1
(
C
95—197 C (CHCl —MeOH). Found (%): C, 55.24; H, 4.13;
1
3
N, 8.01; S, 18.40. C H N O S . Calculated (%): C, 55.47;
H, 4.07; N, 8.09; S, 18.51. IR, /cm : 3492, 3384 (NH ), 3068,
1
1
1
16 14
2
3 2
–
1
4
2
616 (C=O), 1580, 1552, 1444, 1300 (SO ), 1288, 1148 (SO ),
(
2 2
1
124, 1080, 724. H NMR (DMSO-d ),: 2.47 (s, 3 H, 6-CH );
(
6
3
3
2
.67 (s, 3 H, CH C(O)); 6.32 (s, 2 H, NH ); 7.08 (s, 1 H, HTP(4));
S, 14.33. C25H N O S . Calculated (%): C, 67.85; H, 4.10;
3
2
18
2
2 2
–
1
7.58—7.70 (m, 3 H, HPhSO2(3), HPhSO2(4), H
(5)); 7.97
PhSO
2
N, 6.33; S, 14.49. IR, /cm : 3476, 3364 (NH ), 3060, 1572,
2
13
1
(d, 2 H, HPhSO2(2), HPhSO2(6), J = 7.3 Hz). C NMR (DMSO-d ),

1
536, 1512, 1300 (SO ), 1140 (SO ), 1084, 748, 720. H NMR
6
2
2
: 19.66 (6-CH ); 23.75 (CH CO); 100.94 (CTP(2)); 122.34
3 3
(
DMSO-d ),: 5.46 (s, 2 H, NH ); 7.45—7.51 (m, 3 H, H6-Ph(3),
6
2
(
CTP(3a)); 122.41 (CTP(4)); 126.02 (CPhSO2(3), CPhSO2(5));
29.58 (CPhSO2(2), CPhSO2(6)); 133.38 (CPhSO2(4)); 142.01
CPhSO2(1)); 145.92 (CTP(3)); 146.25 (CTP(5)); 159.80 (CTP(6));
160.09 (CTP
H6-Ph(4), H6-Ph(5)); 7.53—7.70 (m, 8 H, HPhSO2(3), HPhSO2(4),
1
HPhSO2(5), and 4-Ph); 7.76 (s, 1 H, HTP(5)); 7.97 (d, 2 H,
(
HPhSO2(2), H
(6), J = 7.3 Hz); 8.12—8.18 (m, 2 H, H6-Ph(2),
PhSO
2
H6-Ph(6)). 13C NMR (DMSO-d ), : 101.88 (CTP(2)); 118.86
(7a)); 193.47 (CH CO).
3
6
Ethyl 3-amino-6-methyl-4-phenyl-2-(phenylsulfonyl)thieno-
(
CTP(5)); 120.38 (CTP(3a)); 126.22 (CPhSO2(3), CPhSO2(5));
27.26 (C6-Ph(3), C6-Ph(5)); 128.62 (C6-Ph(2), C6-Ph(6)); 128.87
C4-Ph(3), C4-Ph(5)); 128.90 (C4-Ph(2), C4-Ph(6)); 129.43 (C4-Ph(4));
29.62 (CPhSO2(2), CPhSO2(6)); 130.15 (C6-Ph(4)); 133.52
[
2,3-b]pyridine-5-carboxylate (3g). The yield was 1 g (55%),
1
yellowish white crystals, m.p. 170—171 C (CHCl —MeOH).
(
1
3
Found (%): C, 61.19; H, 4.33; N, 6.08; S, 14.27. C H N O S .
23 20
2
4
2
1
–
Calculated (%): C, 61.04; H, 4.45; N, 6.19; S, 14.19. IR, /cm
:
(
(
CPhSO2(4)); 135.77 (C4-Ph(1)); 136.92 (C6-Ph(1)); 141.70
CPhSO2(1)); 144.02 (CTP(3)); 148.69 (CTP(4)); 156.49 (CTP(6));
3
496, 3388 (NH ), 3068, 2968, 1728 (C=O), 1604, 1548, 1308
2
1
(
SO ), 1288, 1144 (SO ). H NMR (DMSO-d ),: 0.82 (t, 3 H,
1
60.85 (CTP(7a)).
-(Phenylsulfonyl)-6-phenyl-4-(trifluoromethyl)thieno[2,3-b]-
pyridine-3-amine (3d). The yield was 1.2 g (69%), yellow crystals,
m.p. 260—262 C (CHCl —MeOH). Found (%): C, 55.71;
2
2
6
CH CH O, J = 7.3 Hz); 2.57 (s, 3 H, 6-CH ); 3.93 (q, 2 H,
2
3
2
3
CH CH O, J = 7.3 Hz); 5.26 (s, 2 H, NH ); 7.47 (d, 2 H,
3
2
2
H4-Ph(2), H4-Ph(6), J = 7.3 Hz); 7.50—7.70 (m, 6 H, H4-Ph(3),
3
H4-Ph(4), H4-Ph(5), and HPhSO2(3), H
(4), HPhSO2(5)); 7.93
H, 3.09; N, 6.39; S, 14.63. C20H F N O S . Calculated (%):
PhSO
2
13
3
2
2
2
1
3
(
d, 2 H, HPhSO2(2), HPhSO2(6), J = 8.1 Hz). C NMR (DMSO-d ),
6
*
*
TP is the thienopyridine moiety.
* THTQ is the tetrahydrothienoquinoline moiety.
: 13.31 (CH CH O); 22.70 (6-CH ); 61.24 (CH CH O); 101.81
3 2 3 3 2
(CTP(2)); 119.39 (CTP(3a)); 126.22 (CPhSO2(3), CPhSO2(5)); 127.03

2
-(Organylsulfonyl)thieno[2,3-b]pyridines
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
361
(
CTP(5)); 128.47 (C4-Ph(3), C4-Ph(5)); 128.67 (C4-Ph(2), C4-Ph(6));
29.64 (CPhSO2(2), CPhSO2(6)); 129.67 (C4-Ph(4)); 132.71 (C4-Ph(1));
33.59 (CPhSO2(4)); 141.52 (CPhSO2(1)); 144.10 (CTP(3)); 144.97
CTP(4)); 155.65 (CTP(6)); 160.14 (CTP(7a)); 166.46 (C=O).
-(Benzylsulfonyl)-4,6-dimethylthieno[2,3-b]pyridine-3-amine
3h). The yield was 0.73 g (55%), yellow crystals, m.p. 182—184 C
CHCl —MeOH). Found (%): C, 57.61; H, 4.93; S, 19.21.
CBnSO2(5)); 128.65 (CBnSO2(4)); 129.14 (C6-Ph(2), C6-Ph(6));
1
130.97 (C6-Ph(4)); 131.00 (CBnSO2(2), CBnSO2(6)); 132.98
(q, CTP(4), J = 33.2 Hz); 135.98 (C6-Ph(1)); 143.04 (CTP(3));
157.31 (CTP(6)); 161.86 (CTP(7a)).
1
(
2
2-(Benzylsulfonyl)-6-methyl-4-phenyl-5-(phenylaminocarb-
onyl)thieno[2,3-b]pyridine-3-amine (3l). The yield was 0.88 g
(
(
(43%), light yellow crystals, m.p. 296—298 C (CHCl —MeOH).
3
3
C H N O S . Calculated (%): C, 57.81; H, 4.85; S, 19.29. IR,
Found (%): C, 65.63; H, 4.66; N, 8.24; S, 12.27. C H N O S .
1
6
16
2
2
2
28 23
3
3
2
–
1
1
–1

/cm : 3484, 3368 (NH ), 1320 (SO ), 1144 (SO ). H NMR
Calculated (%): C, 65.48; H, 4.51; N, 8.18; S, 12.48. IR, /cm
:
2
2
2
(
(
7
DMSO-d ),: 2.48 (s, 3 H, 4-CH ); 2.63 (s, 3 H, 6-CH ); 4.62
3483, 3392, 3322 (NH ), 1685 (C=O), 1322 (SO ), 1144 (SO ).
6
3
3
2 2 2
1
s, 2 H, CH SO ); 5.94 (s, 2 H, NH ); 7.06 (s, 1 H, HTP(5));
H NMR (DMSO-d ),: 2.63 (s, 3 H, 6-CH ); 4.58 (s, 2 H,
6 3
2
2
2
13
.20—7.40 (m, 5 H, CH Ph). C NMR (DMSO-d ), : 19.66
CH SO ); 4.73 (s, 2 H, NH ); 7.02 (t, 1 H, HPhN(4), J = 7.3 Hz);
2
6
2 2 2
(
(
(
4-CH ); 23.74 (6-CH ); 61.28 (PhCH ); 99.54 (CTP(2)); 122.04
7.23—7.58 (m, 14 H, HPhN(2), HPhN(3), HPhN(5), HPhN(6),
3
3
2
13
CTP(3a)); 122.26 (CTP(5)); 128.15 (CBnSO2(3), CBnSO2(5)); 128.37
4-Ph, and CH Ph); 10.34 (s, 1 H, NHCO). C NMR (DMSO-d ),
2
6
CBnSO2(4)); 128.64 (CBnSO2(1)); 130.85 (CBnSO2(2), CBnSO2(6));
: 22.47 (6-CH ); 61.08 (PhCH ); 100.41 (CTP(2)); 119.61
3
2
1
45.60 (CTP(3)); 146.92 (CTP(4)); 159.59 (CTP(6)); 160.04 (CTP(7a)).
(CPhN(2), CPhN(6)); 123.98 (CPhN(4)); 126.18 (CTP(3a)); 128.23
(CBnSO2(3), CBnSO2(5)); 128.34 (C4-Ph(3), C4-Ph(5)); 128.45
(CBnSO2(4)); 128.50 (C4-Ph(2), C4-Ph(6)); 128.64 (CPhN(3),
CPhN(5)); 128.67 (CBnSO2(1)); 129.41 (C4-Ph(4)); 130.65 (CTP(5));
130.87 (CBnSO2(2), CBnSO2(6)); 132.64 (CPhN(1)); 138.09
(C4-Ph(1)); 144.11 (CTP(4)); 144.97 (CTP(3)); 155.76 (CTP(6));
159.41 (CTP(7a)); 164.40 (C=O).
2
-(Benzylsulfonyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-
-amine (3i). The yield was 1.03 g (72%), yellow crystals, m.p.
01—203 C (CHCl —MeOH). Found (%): C, 60.18; H, 5.00;
3
2
3
N, 7.90; S, 18.14. C H N O S . Calculated (%): C, 60.31;
18
18
2
2 2
–
1
H, 5.06; N, 7.81; S, 17.89. IR, /cm : 3448, 3304 (NH ), 3176,
2
2
6
2
932, 2864, 1632, 1560, 1396, 1300 (SO ), 1140 (SO ), 1112, 796,
2 2
1
96. H NMR (DMSO-d ),: 1.80—2.00 (m, 4 H, 6,7-CH2THTQ);
.88 (t, 2 H, 5-CH2THTQ, J = 5.9 Hz); 2.98 (t, 2 H, 8-CH2THTQ
5-Acetyl-2-(benzylsulfonyl)-6-methylthieno[2,3-b]pyridine-
3-amine (3m). The yield was 0.59 g (41%), light yellow crystals,
6
,
J = 5.9 Hz); 4.40 (s, 2 H, CH SO ); 4.92 (s, 2 H, NH ); 7.17—7.33
m.p. 188—190 C (CHCl —MeOH). Found (%): C, 56.82;
2
2
2
3
13
(

m, 5 H, CH Ph); 7.48 (s, 1 H, HTHTQ(4)). C NMR (DMSO-d ),
H, 4.54; N, 7.91; S, 17.66. C H N O S . Calculated (%):
17 16 2 3 2
2
6
–
1
: 22.14 (6-CH2THTQ); 22.30 (7-CH2THTQ); 28.30 (5-CH2THTQ);
C, 56.65; H, 4.47; N, 7.77; S, 17.79. IR, /cm : 3444, 3360 (NH ),
2
3
2.49 (8-CH2THTQ); 61.25 (PhCH ); 96.37 (CTHTQ(2)); 123.73
3072, 2908, 1616 (C=O), 1584, 1552, 1296 (SO ), 1148 (SO ),
2
2
2
1
(
CTHTQ(3a)); 128.20 (CBnSO2(3), CBnSO2(5)); 128.38 (CBnSO2(4));
1104, 808. H NMR (DMSO-d ),: 2.50 (s, 3 H, 6-CH ); 2.66
6
3
1
28.85 (CTHTQ(4a)); 128.93 (CBnSO2(1)); 130.86 (CBnSO2(2),
(s, 3 H, CH C(O)); 4.61 (s, 2 H, CH SO ); 7.08 (s, 1 H, HTP(4));
3 2 2
13
CBnSO2(6)); 131.70 (CTHTQ(4)); 145.22 (CTHTQ(3)); 156.72
7.20—7.40 (m, 5 H, CH Ph). C NMR (DMSO-d ), : 19.75
2
6
(
CTHTQ(9a)); 159.90 (CTHTQ(8a)).
-(Benzylsulfonyl)-4,6-diphenylthieno[2,3-b]pyridine-3-amine
3j). The yield was 1.04 g (57%), light yellow crystals, m.p.
14—216 C (CHCl —MeOH). Found (%): C, 68.28; H, 4.50;
(6-CH ); 23.92 (CH CO); 61.35 (PhCH ); 98.25 (CTP(2)); 122.13
3 3 2
2
(CTP(3a)); 122.36 (CTP(4)); 128.25 (CBnSO2(3), CBnSO2(5));
128.49 (CBnSO2(4)); 128.71 (CBnSO2(1)); 130.95 (CBnSO2(2),
CBnSO2(6)); 145.69 (CTP(3)); 147.01 (CTP(5)); 159.71 (CTP(6));
(
2
3
N, 6.23; S, 14.33. C26H20N O S . Calculated (%): C, 68.40;
160.11 (CTP(7a)); 193.98 (CH CO).
2
2
2
3
–
1
H, 4.42; N, 6.14; S, 14.05. IR, /cm : 3496, 3384 (NH ), 3060,
2-(Butylsulfonyl)-4,6-dimethylthieno[2,3-b]pyridine-3-amine
(3n). The yield was 0.88 g (74%), yellow crystals, m.p. 105—107 C
2
2
8
968, 2920, 1608, 1572, 1536, 1388, 1304 (SO ), 1140 (SO ), 1116,
2 2
1
76, 796, 756, 712. H NMR (DMSO-d ), : 4.63 (s, 2 H,
(CHCl —MeOH) (cf. Ref. 3: m.p. 105—107 C (MeOH)).
6
3
CH SO ); 5.03 (s, 2 H, NH ); 7.18—7.32 (m, 5 H, CH Ph);
Found (%): C, 52.45; H, 6.12; N, 9.48; S, 21.33. C H N O S .
2
2
2
2
13 18
2
2
2
1
–
7
.48—7.57 (m, 5 H, 4-Ph); 7.59—7.68 (m, 3 H, H6-Ph(3),
Calculated (%): C, 52.32; H, 6.08; N, 9.39; S, 21.49. IR, /cm
:
H6-Ph(4), H6-Ph(5)); 7.83 (s, 1 H, HTP(5)); 8.17—8.25 (m, 2 H,
3492, 3380 (NH ), 2960, 2872, 1612, 1552, 1512, 1456, 1392,
2
13
1
H6-Ph(2), H6-Ph(6)). C NMR (DMSO-d ), : 61.25 (PhCH );
1276 (SO ), 1144 (SO ), 1112, 808. H NMR (DMSO-d ),: 0.93
6
2
2
2
6
9
9.33 (CTP(2)); 118.78 (CTP(5)); 120.12 (CTP(3a)); 127.36
CBnSO2(3), CBnSO2(5)); 128.32 (CPh(3), CPh(5), CPh(6)); 128.50
CBnSO2(4)); 128.65 (C6-Ph(2), C6-Ph(6)); 128.70 (CBnSO2(1));
(t, 3 H, CH CH CH CH , J = 7.3 Hz); 1.27—1.40 (m, 2 H,
3 2 2 2
(
(
CH CH CH CH ); 1.57—1.70 (m, 2 H, CH CH CH CH ); 2.55
3 2 2 2 3 2 2 2
(s, 3 H, 4-CH ); 2.70 (s, 3 H, 6-CH ); 3.22 (t, 2 H, CH CH -
3
3
3
2
1
28.90 (C4-Ph(3), C4-Ph(5)); 128.98 (C4-Ph(2), C4-Ph(6)); 129.49
C4-Ph(4)); 130.23 (C6-Ph(4)); 131.04 (CBnSO2(2), CBnSO2(6));
35.81 (C4-Ph(1)); 137.04 (C6-Ph(1)); 144.90 (CTP(3)); 148.63
CTP(4)); 156.48 (CTP(6)); 160.85 (CTP(7a)).
-(Benzylsulfonyl)-6-phenyl-4-(trifluoromethyl)thieno[2,3-b]-
pyridine-3-amine (3k). The yield was 0.55 g (31%), yellow crystals,
m.p. 210—212 C (CHCl —MeOH). Found (%): C, 56.43;
CH CH , J = 7.3 Hz); 5.15 (s, 2 H, NH ); 6.87 (s, 1 H, HTP(5)).
2
2
2
13
(
C NMR (DMSO-d ), : 13.43 (CH CH CH CH ); 19.74
6 3 2 2 2
1
(4-CH ); 20.75 (CH CH CH CH ); 23.61 (6-CH ); 24.50
3 3 2 2 2 3
(
(CH CH CH CH ); 55.53 (CH CH CH CH ); 99.34 (CTP(2));
3 2 2 2 3 2 2 2
2
122.42 (CTP(5)); 122.51 (CTP(3a)); 145.78 (CTP(3)); 146.45
(CTP(4)); 159.65 (C(6) TP); 159.88 (CTP(7a)).
2-(Butylsulfonyl)-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-
3-amine (3o). The yield was 0.92 g (71%), light yellow crystals,
m.p. 228—230 C (MeOH). Found (%): C, 55.41; H, 6.29;
3
H, 3.41; N, 6.18; S, 14.22. C H F N O S . Calculated (%):
21
15
3
2
2
2
–
1
C, 56.24; H, 3.37; N, 6.25; S, 14.30. IR, /cm : 3484, 3392 (NH ),
2
1
1
312 (SO ), 1140 (SO ). H NMR (DMSO-d ),: 4.75 (s, 2 H,
N, 8.75; S, 19.59. C H N O S . Calculated (%): C, 55.53; H, 6.21;
2
2
6
15 20 2 2 2
–
1
CH SO ); 5.73 (s, 2 H, NH ); 7.20—7.35 (m, 5 H, CH Ph),
N, 8.63; S, 19.76. IR, /cm : 3452, 3296 (NH ), 3158, 2932,
2
2
2
2
2
7
.55—7.62 (m, 3 H, H6-Ph(3), H6-Ph(4), H6-Ph(5)); 8.22—8.30
2868, 1632, 1568, 1396, 1296 (SO ), 1124 (SO ), 1000, 800.
2 2
13
1
(
(
m, 2 H, H6-Ph(2), H6-Ph(6)); 8.33 (s, 1 H, HTP(5)). C NMR
DMSO-d ), : 61.27 (PhCH ); 103.76 (CTP(2)); 114.39 (q, CTP(5),
H NMR (DMSO-d ), : 0.93 (t, 3 H, CH CH CH CH ,
6 3 2 2 2
J = 7.3 Hz); 1.27—1.40 (m, 2 H, CH CH CH CH ); 1.57—1.70
6
2
3
2
2
2
J = 6.6 Hz); 119.15 (q, CF , J
= 226.7 Hz); 124.28 (CTP(3a));
(m, 2 H, CH CH CH CH ); 1.73—1.95 (m, 4 H, 6,7-CH2THTQ),
3
C,F
3 2 2 2
1
27.57 (C6-Ph(3), C6-Ph(5)); 128.30 (CBnSO2(1)); 128.36 (CBnSO2(3),
2.88 (t, 2 H, 5-CH2THTQ, J = 5.9 Hz); 2.95 (t, 2 H, 8-CH2THTQ,

3
62
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Kalugin and Shestopalov
J = 5.9 Hz); 3.29 (t, 2 H, CH CH CH CH , J = 7.3 Hz); 6.77
(CPhN(3), CPhN(5)); 129.47 (C4-Ph(4)); 130.81 (CTP(5)); 132.76
(CPhN(1)); 138.11 (C4-Ph(1)); 144.14 (CTP(4)); 144.33 (CTP(3));
155.74 (CTP(6)); 159.30 (CTP(7a)); 164.47 (C=O).
3
2
2
2
1
3
(
s, 2 H, NH ); 8.26 (s, 1 H, HTHTQ(4)). C NMR (DMSO-d ),
2
6

(
2
: 13.45 (CH CH CH CH ); 20.75 (CH CH CH CH ); 22.14
3 2 2 2 3 2 2 2
6-CH2THTQ); 22.31 (7-CH2THTQ); 24.58 (CH CH CH CH );
5-Acetyl-2-(butylsulfonyl)-6-methylthieno[2,3-b]pyridine-3-
amine (3s). The yield was 0.76 g (58%), light yellow crystals, m.p.
3
2
2
2
8.30 (5-CH2THTQ); 32.47 (8-CH2THTQ); 55.39 (CH CH -
3 2
CH CH ); 97.14 (CTHTQ(2)); 124.06 (CTHTQ(3a)); 128.88
108—109 C (CHCl —MeOH). Found (%): C, 51.62; H, 5.48;
2
2
3
(
(
CTHTQ(4a)); 131.74 (CTHTQ(4)); 144.59 (CTHTQ(3)); 156.73
CTHTQ(9a)); 159.76 (CTHTQ(8a)).
N, 8.67; S, 19.55. C H N O S . Calculated (%): C, 51.51;
14 18 2 3 2
–
1
H, 5.56; N, 8.58; S, 19.64. IR, /cm : 3492, 3380 (NH ), 2956,
2
1
2
-(Butylsulfonyl)-4,6-diphenylthieno[2,3-b]pyridine-3-amine
3p). The yield was 1.08 g (64%), yellow crystals, m.p. 127—129 C
CHCl —MeOH). Found (%): C, 65.55; H, 5.21; N, 6.70;
1616 (C=O), 1608, 1584, 1552, 1272, 1140 (SO ), 804. H NMR
2
(
(
(DMSO-d ),: 0.83 (t, 3 H, CH CH CH CH , J = 7.3 Hz);
6 3 2 2 2
1.28—1.42 (m, 2 H, CH CH CH CH ); 1.55—1.67 (m, 2 H,
3 2 2 2
3
S, 15.36. C H N O S . Calculated (%): C, 65.38; H, 5.25;
CH CH CH CH ); 2.50 (s, 3 H, CH C(O)); 2.72 (s, 3 H,
2
3
22
2
2
2
3 2 2 2 3
–
1
N, 6.63; S, 15.17. IR, /cm : 3468, 3368 (NH ), 2964, 2936,
6-CH ); 3.30 (t, 2 H, CH CH CH CH , J = 7.3 Hz); 6.13 (s, 2 H,
3 3 2 2 2
2
13
2
872, 1608, 1576, 1536, 1510, 1392, 1296, 1116, 768, 708, 692.
NH ); 7.10 (s, 1 H, HTP(4)). C NMR (DMSO-d ), : 13.39
2
6
1
H NMR (DMSO-d ), : 0.83 (t, 3 H, CH CH CH CH ,
(CH CH CH CH ); 19.72 (6-CH ); 20.75 (CH CH CH CH );
3 2 2 2 3 3 2 2 2
6
3
2
2
2
J = 7.3 Hz); 1.27—1.42 (m, 2 H, CH CH CH CH ); 1.60—1.72
23.78 (CH CO); 24.48 (CH CH CH CH ); 55.54 (CH CH -
3
2
2
2
3 3 2 2 2 3 2
(
m, 2 H, CH CH CH CH ); 3.30 (t, 2 H, CH CH CH CH ,
CH CH ); 99.36 (CTP(2)); 122.35 (CTP(4)); 122.47 (CTP(3a));
2 2
3
2
2
2
3
2
2
2
J = 7.3 Hz); 5.30 (s, 2 H, NH ); 7.48—7.55 (m, 3 H, H6-Ph(3),
145.69 (CTP(3)); 146.42 (CTP(5)); 159.59 (CTP(6)); 159.87
2
H6-Ph(4), H6-Ph(5)); 7.56—7.64 (m, 5 H, 4-Ph); 7.83 (s, 1 H,
(CTP(7a)); 193.38 (CH CO).
3
1
3
HTP(5)); 8.17—8.24 (m, 2 H, H6-Ph(2), H6-Ph(6)). C NMR
Ethyl 3-amino-2-(butylsulfonyl)-6-methyl-4-phenylthieno-
(
DMSO-d ), : 13.42 (CH CH CH CH ); 20.76 (CH CH -
[2,3-b]pyridine-5-carboxylate (3t). The yield was 0.9 g (52%),
6
3
2
2
2
3
2
CH CH ); 24.38 (CH CH CH CH ); 55.25 (CH CH CH CH );
light yellow crystals, m.p. 86—88 C (CHCl —MeOH). Found (%):
2
2
3
2
2
2
3
2
2
2
3
1
(
00.50 (CTP(2)); 118.83 (CTP(5)); 120.54 (CTP(3a)); 127.30
C6-Ph(3), C6-Ph(5)); 128.69 (C6-Ph(2), C6-Ph(6)); 128.88 (C4-Ph(3),
C4-Ph(5)); 128.91 (C4-Ph(2), C4-Ph(6)); 129.43 (C4-Ph(4)); 130.13
C6-Ph(4)); 135.92 (C4-Ph(1)); 137.05 (C6-Ph(1)); 144.19 (CTP(3));
48.57 (CTP(4)); 156.37 (CTP(6)); 160.67 (CTP(7a)).
-(Butylsulfonyl)-6-phenyl-4-(trifluoromethyl)thieno[2,3-b]-
pyridine-3-amine (3q). The yield was 0.95 g (57%), yellow crystals,
m.p. 150—152 C (CHCl —MeOH). Found (%): C, 52.34; H, 4.20;
C, 58.52; H, 5.48; N, 6.37; S, 14.71. C H N O S . Calculat-
21 24 2 4 2
–
1
ed (%): C, 58.31; H, 5.59; N, 6.48; S, 14.82. IR, /cm : 3492,
3388 (NH ), 2936, 1728 (C=O), 1596, 1548, 1296 (SO ), 1120
2
2
1
(
1
(SO ), 1100, 1024, 768. H NMR (DMSO-d ),: 0.83 (t, 3 H,
2
6
CH CH CH CH , J = 7.3 Hz); 0.87 (t, 3 H, CH CH O, J = 7.3 Hz);
3 2 2 2 3 2
2
1.28—1.37 (m, 2 H, CH CH CH CH ); 1.56—1.68 (m, 2 H,
3 2 2 2
CH CH CH CH ); 2.62 (s, 3 H, 6-CH ); 3.27 (t, 2 H, CH CH
2-
3
2
2
2
3
3
CH CH , J = 7.3 Hz); 3.96 (q, 2 H, CH CH O, J = 7.3 Hz);
3
2
2
3
2
N, 6.83; S, 15.22. C H F N O S . Calculated (%): C, 52.16;
5.07 (s, 2 H, NH ); 7.37—7.46 (m, 2 H, H
(2), H4-Ph(6));
1
8
17
3
2
2
2
2
4-Ph
–
1
13
H, 4.13; N, 6.76; S, 15.47. IR, /cm : 3516, 3392 (NH ), 2960,
7.52—7.62 (m, 3 H, H4-Ph(3), H4-Ph(4), H4-Ph(5)). C NMR
2
2
1
872, 1624, 1588, 1512, 1372, 1312, 1296 (SO ), 1260, 1192, 1168,
(DMSO-d ), : 13.34 (CH CH CH CH ); 13.39 (CH CH O);
2
6 3 2 2 2 3 2
1
142, 1116 (SO ), 780, 764. H NMR (DMSO-d ),: 0.83 (t, 3 H,
20.69 (CH CH CH CH ); 22.72 (6-CH ); 24.32 (CH CH -
3 2 2 2 3 3 2
2
6
CH CH CH CH , J = 7.3 Hz); 1.30—1.43 (m, 2 H, CH CH CH -
CH CH ); 55.13 (CH CH CH CH ); 61.30 (CH CH O); 100.52
3
2
2
2
3
2
2
2 2 3 2 2 2 3 2
CH ); 1.60—1.74 (m, 2 H, CH CH CH CH ); 3.42 (t, 2 H,
(CTP(2)); 119.55 (CTP(3a)); 126.98 (CTP(5)); 128.50 (C4-Ph(3),
C4-Ph(5)); 128.68 (C4-Ph(2), C4-Ph(6)); 129.68 (C4-Ph(4)); 132.87
(C4-Ph(1)); 144.29 (CTP(3)); 144.85 (CTP(4)); 155.42 (CTP(6));
160.02 (CTP(7a)); 166.63 (C=O).
2
3
2
2
2
CH CH CH CH , J = 7.3 Hz); 5.96 (s, 2 H, NH ); 7.54—7.60
3
2
2
2
2
(
m, 3 H, H6-Ph(3), H6-Ph(4), H6-Ph(5)); 8.22—8.30 (m, 2 H,
1
3
H6-Ph(2), H6-Ph(6)); 8.33 (s, 1 H, HTP(5)). C NMR (DMSO-d6),
: 13.37 (CH CH CH CH ); 20.71 (CH CH CH CH ); 24.26

4,6-Dimethyl-2-(morpholin-4-ylsulfonyl)thieno[2,3-b]pyrid-
ine-3-amine (3u). The yield was 0.6 g (46%), yellow crystals, m.p.
196—198 C (MeOH). Found (%): C, 47.78; H, 5.18; N, 12.88;
3
2
2
2
3
2
2
2
(
CH CH CH CH ); 55.28 (CH CH CH CH ); 104.10 (CTP(2));
3 2 2 2 3 2 2 2
1
14.39 (q, CTP(5), J = 6.6 Hz); 119.05 (q, CF , J
= 225.6 Hz);
C,F
3
1
24.31 (CTP(3a)); 127.53 (C6-Ph(3), C6-Ph(5)); 129.11 (C6-Ph(2),
C6-Ph(6)); 130.93 (C6-Ph(4)); 132.93 (q, CTP(4), J = 33.2 Hz);
36.01 (C6-Ph(1)); 142.39 (CTP(3)); 157.24 (CTP(6)); 161.64 (CTP(7a)).
-(Butylsulfonyl)-6-methyl-4-phenyl-5-(phenylaminocarb-
onyl)thieno[2,3-b]pyridine-3-amine (3r). The yield was 1.3 g
68%), porcelain crystals, m.p. 262—263 C (CHCl —MeOH).
S, 19.50. C H N O S . Calculated (%): C, 47.69; H, 5.23;
13 17 3 3 2
–
1
N, 12.83; S, 19.58. IR, /cm : 3419, 3346 (NH ), 2969, 2862,
2
1
1631, 1581, 1449, 1378, 1328 (SO ), 1264, 1149 (SO ), 1112, 1069,
2 2
1
2
938, 793, 726. H NMR (DMSO-d ),: 2.52 (s, 3 H, 4-CH );
6 3
2.73 (s, 3 H, 6-CH ); 3.08 (t, 4 H, CH NCH , J = 4.4 Hz); 3.65
3
2
2
(
(t, 4 H, CH OCH , J = 4.4 Hz); 6.05 (s, 2 H, NH ); 7.12 (s, 1 H,
3
2
2
2
1
3
Found (%): C, 62.54; H, 5.16; N, 8.62; S, 13.22. C H N O S .
HTP(5)). C NMR (DMSO-d ), : 19.76 (4-CH ); 23.77
6 3
2
5
25
3
3
2
Calculated (%): C, 62.61; H, 5.25; N, 8.76; S, 13.37. IR,
(6-CH ); 46.00 (CH NCH ); 65.29 (CH OCH ); 96.01 (CTP(2));
3 2 2 2 2
–
1
1

(
1
/cm : 3516, 3392 (NH ), 1312 (SO ), 1140 (SO ). H NMR
122.42 (CTP(5)); 122.53 (CTP(3a)); 145.57 (CTP(3)); 146.21
(CTP(4)); 159.41 (CTP(7a)); 159.48 (CTP(6)).
2
2
2
DMSO-d ),: 0.83 (t, 3 H, CH CH CH CH , J = 7.3 Hz);
6 3 2 2 2
.27—1.41 (m, 2 H, CH CH CH CH ); 1.54—1.67 (m, 2 H,
2-(Morpholin-4-ylsulfonyl)-4,6-diphenylthieno[2,3-b]pyridi-
ne-3-amine (3v). The yield was 0.72 g (44%), light yellow crystals,
3
2
2
2
CH CH CH CH ); 2.62 (s, 3 H, 6-CH ); 3.32 (t, 2 H, CH CH -
3
2
2
2
3
3
2
CH CH , J = 7.3 Hz); 5.06 (s, 2 H, NH ); 7.04 (t, 1 H, HPhN(4),
m.p. 204—206 C (CHCl —MeOH). Found (%): C, 61.11; H,
2
2
2
3
J = 7.3 Hz); 7.26 (t, 2 H, HPhN(3), HPhN(5), J = 7.3 Hz); 7.32
4.71; N, 9.34; S, 14.26. C H N O S . Calculated (%): C, 61.18;
23
21
3
3
2
1
–
(
1
d, 2 H, HPhN(2), HPhN(6), J = 7.3 Hz); 7.44—7.54 (m, 5 H, 4-Ph);
H, 4.69; N, 9.31; S, 14.20. IR, /cm : 3485, 3371 (NH ), 3061,
2
13
0.38 (s, 1 H, NHCO). C NMR (DMSO-d ), : 13.44 (CH -
1604, 1575, 1535, 1513, 1388, 1328 (SO ), 1264, 1169, 1145 (SO ),
6
3
2
2
1
CH CH CH ); 20.69 (CH CH CH CH ); 22.45 (6-CH ); 24.43
1108, 1070, 936, 758, 707. H NMR (DMSO-d ),: 3.14 (t, 4 H,
6
2
2
2
3
2
2
2
3
(
1
CH CH CH CH ); 55.05 (CH CH CH CH ); 100.12 (CTP(2));
CH NCH , J = 4.4 Hz); 3.65 (t, 4 H, CH OCH , J = 4.4 Hz);
3
2
2
2
3
2
2
2
2 2 2 2
19.64 (CPhN(2), CPhN(6)); 124.03 (CPhN(4)); 126.13 (CTP(3a));
5.20 (s, 2 H, NH ); 7.47—7.55 (m, 3 H, H6-Ph(3), H6-Ph(4), H6-
2
128.46 (C4-Ph(3), C4-Ph(5)); 128.60 (C4-Ph(2), C4-Ph(6)); 128.69
Ph(5)); 7.57—7.62 (m, 5 H, 4-Ph); 7.83 (s, 1 H, HTP(5));

2
-(Organylsulfonyl)thieno[2,3-b]pyridines
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
363
8
.17—8.25 (m, 2 H, H6-Ph(2), H6-Ph(6)). 13C NMR (DMSO-d ),
(s, 0.6 H, 6-CH , 7a); 2.61 (s, 2.4 H, 4-CH , 6a); 2.73 (s, 2.4 H,
3 3
6

: 46.00 (CH NCH ); 65.31 (CH OCH ); 96.94 (CTP(2)); 118.86
6-CH , 6a); 5.21 (s, 0.2 H, HTP(2), 7a); 6.77 (s, 0.2 H, HTP(5),
2
2
2
2
3
(
(
(
(
CTP(5)); 120.56 (CTP(3a)); 127.28 (C6-Ph(3), C6-Ph(5)); 128.74
C4-Ph(3), C4-Ph(5)); 128.87 (C4-Ph(2), C4-Ph(6)); 128.94
C6-Ph(2), C6-Ph(6)); 129.37 (C4-Ph(4)); 130.11 (C6-Ph(4)); 136.05
C4-Ph(1)); 137.11 (C6-Ph(1)); 143.97 (CTP(3)); 148.42 (CTP(4));
7a); 6.91 (s, 0.8 H, HTP(5), 6a); 7.50—7.70 (m, 3 H, HPhSO2(3),
HPhSO2(4), HPhSO2(5)); 7.95 (d, 0.4 H, HPhSO2(2), HPhSO2(6),
J = 7.3 Hz, 7a), 8.00 (d, 1.6 H, H
(2), HPhSO2(6), J = 7.3 Hz,
PhSO
2
13
6a); 9.56 (br.s, 0.8 H, 3-OH, 6a). C NMR (DMSO-d ), : 17.53
6
1
56.25 (CTP(6)); 160.27 (CTP(7a)).
-Amino-4,6-dimethyl-N-phenylthieno[2,3-b]pyridine-2-sulfon-
amide (3w). The yield was 0.48 g (36%), yellow crystals, m.p.
07—208 C (MeOH). Found (%): C, 54.11; H, 4.48; N, 12.53;
S, 19.35. C H N O S . Calculated (%): C, 54.03; H, 4.53; N, 12.60;
(4-CH , 7a); 18.69 (4-CH , 6a); 23.99 (6-CH , 6a); 24.14
3 3 3
3
(6-CH , 7a); 72.38 (CTP(2), 7a); 112.24 (CTP(2), 6a); 120.83
3
(CTP(3a), 7a); 122.72 (CTP(5), 6a, 7a); 123.68 (CTP(3a), 6a);
126.82 (CPhSO2(3), CPhSO2(5), 6a, 7a), 129.32 (CPhSO2(2),
CPhSO2(6), 7a), 129.62 (CPhSO2(2), CPhSO2(6), 6a), 133.84
(CPhSO2(4), 6a), 134.90 (CPhSO2(4), 7a), 141.65 (CPhSO2(1), 6a),
142.23 (CPhSO2(1), 7a), 146.35 (CTP(3), 6a); 151.97 (CTP(4), 7a);
152.27 (CTP(4), 6a); 158.25 (CTP(6a), 6a); 160.07 (CTP(6), 6a);
166.14 (CTP(6), 7a); 171.32 (CTP(7a), 7a); 189.15 (CTP(3), 7a).
2-(Benzylsulfonyl)-4,6-dimethylthieno[2,3-b]pyridine-3-ol
(6b) and 2-(benzylsulfonyl)-4,6-dimethylthieno[2,3-b]pyridine-
3(2H)-one (7b) (6b : 7b = 68 : 32). The yield was 0.23 g (23%),
pink crystals, m.p. 115.5—117 C (MeOH). Found (%): C, 57.81;
2
15
15
3 2 2
–
1
S, 19.23. IR, /cm : 3508, 3388 (NH ), 2981, 2751, 2685, 1608,
2
1
6
6
548, 1510, 1495, 1317 (SO ), 1301, 1145 (SO ), 1116, 1010, 943,
2 2
1
97. H NMR (DMSO-d ),: 2.46 (s, 3 H, 4-CH ); 2.67 (s, 3 H,
6
3
-CH ); 6.01 (s, 2 H, NH ); 6.98—7.10 (m, 2 H, HPhN(4),
3
2
HTP(5)); 7.14 (d, 2 H, HPhN(2), HPhN(6), J = 7.3 Hz); 7.24
t, 2 H, HPhN(3), HPhN(5), J = 7.3 Hz); 10.43 (br.s, 1 H, NHSO2).
(
1
3
C NMR (DMSO-d ), : 19.71 (4-CH ); 23.72 (6-CH ); 100.95
6
3
3
(
(
(
CTP(2)); 119.75 (CPhN(2), CPhN(6)); 122.23 (CTP(5)); 122.39
CTP(3a)); 123.99 (CPhN(4)); 129.13 (CPhN(3), CPhN(5)); 137.60
CPhN(1)); 144.68 (CTP(3)); 145.29 (CTP(4)); 159.16 (CTP(6));
H, 4.62; N, 4.38; S, 19.14. C H NO S . Calculated (%):
16 15 3 2
–1
C, 57.64; H, 4.53; N, 4.20; S, 19.23. IR, /cm : 3328 (OH), 3068,
2955, 2916, 1584, 1564, 1508, 1312 (SO ), 1204, 1152 (SO ), 1092,
1
59.22 (CTP(7a)).
-Amino-4,6-diphenyl-N-phenylthieno[2,3-b]pyridine-2-sulfon-
amide (3x). The yield was 0.56 g (32%), yellow crystals, m.p.
90—192 C (MeOH). Found (%): C, 65.51; H, 4.12; N, 9.27;
S, 14.08. C25H N O S . Calculated (%): C, 65.62; H, 4.19;
2
2
1
3
1020, 828, 760, 700. H NMR (CDCl ), : 2.58 (s, 3 H, 4-CH ,
3
3
6b, 7b); 2.62 (s, 0.96 H, 6-CH , 7b); 2.65 (s, 2.04 H, 6-CH ,
3
3
1
6b); 4.48 (s, 2 H, CH SO ); 5.06 (s, 0.32 H, HTP(2), 7b); 6.87
2 2
(s, 0.32 H, HTP(5), 7b); 6.99 (s, 0.68 H, HTP(5), 6b); 7.20—7.44
19
3
2 2
–1
13
N, 9.18; S, 14.01. IR, /cm : 3499, 3398, 3253 (NH ), 3058, 1608,
1
6
(m, 5 H, CH Ph), 8.82 (br.s, 0.68 H, 3-OH, 6b). C NMR
2
2
573, 1536, 1496, 1315 (SO ), 1299, 1136 (SO ), 1002, 918, 750,
(DMSO-d ), : 17.66 (4-CH , 7b); 18.73 (4-CH , 6b); 23.97
2
2
6 3 3
1
93. H NMR (DMSO-d ),: 5.13 (s, 2 H, NH ); 7.04 (t, 1 H,
(6-CH , 6b); 24.31 (6-CH , 7b); 57.30 (PhCH , 7b); 61.45
3 3 2
6
2
HPhN(4), J = 6.6 Hz); 7.15 (d, 2 H, HPhN(2), HPhN(6), J = 7.3 Hz);
.25 (t, 2 H, HPhN(3), HPhN(5), J = 7.3 Hz); 7.37—7.56 (m, 5 H,
-Ph); 7.59—7.65 (m, 3 H, H6-Ph(3), H6-Ph(4), H6-Ph(5)); 7.76
s, 1 H, HTP(5)); 8.12—8.22 (m, 2 H, H6-Ph(2), H6-Ph(6)); 10.43
(PhCH , 6b); 69.90 (CTP(2), 7b); 109.61 (CTP(2), 6b); 120.82
2
7
4
(CTP(3a), 7b); 122.54 (CTP(5), 6b); 123.05 (CTP(5), 7b); 123.87
(CTP(3a), 6b); 128.38 (CBnSO2(3), CBnSO2(5)); 128.70 (CBnSO2(4));
130.95 (CBnSO2(2), CBnSO2(6)); 131.48 (CBnSO2(1)); 146.17
(CTP(3), 6b); 151.87 (CTP(4), 7b); 152.42 (CTP(4), 6b); 158.32
(CTP(7a), 6b); 159.91 (CTP(6), 6b); 166.37 (CTP(6), 7b); 171.76
(CTP(7a), 7b); 189.68 (C(3), 7b).
(
(
13
br.s, 1 H, NHSO ). C NMR (DMSO-d ), : 101.73 (CTP(2));
2
6
1
18.76 (CTP(5)); 119.98 (CPhN(2), CPhN(6)); 120.27 (CTP(3a));
1
24.13 (CPhN(4)); 127.21 (C6-Ph(3), C6-Ph(5)); 128.67 (C6-Ph(2),
C6-Ph(6)), 128.83 (C4-Ph(3), C4-Ph(5)); 128.86 (C4-Ph(2), C4-Ph(6));
2-(Butylsulfonyl)-4,6-dimethylthieno[2,3-b]pyridine-3-ol (6c)
and 2-(butylsulfonyl)-4,6-dimethylthieno[2,3-b]pyridine-3(2H)-
one (7c) (6c : 7c = 83 : 17). The yield was 0.37 g (41%), pink
crystals, m.p. 60—62 C (MeOH). Found (%): C, 52.35; H, 5.88;
1
29.13 (CPhN(3), CPhN(5)); 129.37 (C4-Ph(4)); 130.02 (C6-Ph(4));
1
35.89 (C4-Ph(1)); 137.05 (C6-Ph(1)); 137.47 (CPhN(1)); 142.74
CTP(3)); 148.15 (CTP(4)); 156.07 (CTP(6)); 159.95 (CTP(7a)).
,6-Dimethyl-2-(organylsulfonyl)thieno[2,3-b]pyridine-3-oles
6a—e) and 4,6-dimethyl-2-(organylsulfonyl)thieno[2,3-b]pyrid-
(
4
N, 4.55; S, 21.64. C H NO S . Calculated (%): C, 52.15;
13 17 3 2
–
1
(
H, 5.72; N, 4.68; S, 21.42. IR, /cm : 3396 (OH), 2970, 2956,
ine-3(2H)-ones (7a—e) (general procedure). Anhydrous K CO
2928, 2870, 1707 (C=O), 1587, 1564, 1509, 1312 (SO ), 1242,
2
3
2
1
(
0.53 g, 4.5 mmol) was added under stirring at 50 C to a solution
1192, 1140 (SO ), 1094, 1023, 820, 764, 764, 651. H NMR
2
of methyl 4,6-dimethylpyridin-2(1H)-thione-3-carboxylate 5
(CDCl ), : 0.95 (t, 2.5 H, CH CH CH CH , J = 7.3 Hz, 6c);
3
3
2
2
2
(
0.59 g, 3 mmol)11 and chloromethyl organyl sulfone 2a—e (3 mmol)
1.02 (t, 0.5 H, CH CH CH CH , J = 7.3 Hz, 7c); 1.40—1.54
3 2 2 2
in DMF (5 mL). The reaction mixture was stirred at 75—80 C
(m, 1.66 H, CH CH CH CH , 6c); 1.54—1.61 (m, 0.34 H,
3 2 2 2
for 50 min, cooled to room temperature, and poured into water
CH CH CH CH , 7c); 1.76—1.86 (m, 1.66 H, CH CH CH CH ,
3 2 2 2 3 2 2 2
(
30 mL). The resulting solution was acidified with AcOH, and
6c); 1.90—2.01 (m, 0.34 H, CH CH CH CH , 7c); 2.59 (s, 0.5 H,
3 2 2 2
the product was extracted with CHCl (3×15 mL). The extract
4-CH , 7c); 2.60 (s, 0.5 H, 6-CH , 7c); 2.67 (s, 2.5 H, 4-CH ,
3
3 3 3
was washed with H O (3×20 mL) and dried over MgSO , the
6c); 2.75 (s, 2.5 H, 6-CH , 6c); 3.29 (t, 1.66 H, CH CH CH CH ,
3 3 2 2 2
2
4
solvent was evaporated, and the product was purified by chrom-
J = 8.1 Hz, 6c); 3.43 (t.d, 0.34 H, CH CH CH CH , J = 8.1 Hz,
3 2 2 2 1
atography on silica gel. The eluent was CHCl . The eluate was
J2 = 2.9 Hz, 7c); 5.16 (s, 0.17 H, HTP(2), 7c); 6.88 (s, 0.17 H,
HTP(5), 7c); 7.05 (s, 0.83 H, HTP(5), 6c); 9.44 (br.s, 0.83 H,
3
evaporated, and the product was recrystallized from methanol.
1
3
4
,6-Dimethyl-2-(phenylsulfonyl)thieno[2,3-b]pyridine-3-ol
3-OH, 6c). C NMR (DMSO-d ), : 13.37 (CH CH CH CH );
6 3 2 2 2
(
3
6a) and 4,6-dimethyl-2-(phenylsulfonyl)thieno[2,3-b]pyridine-
(2H)-one (7a) (6a : 7a = 80 : 20). The yield was 0.49 g (51%),
pink crystals, m.p. 143.5—145 C (MeOH). Found (%): C, 56.57;
H, 4.22; N, 4.30; S, 20.15. C H NO S . Calculated (%):
17.56 (4-CH , 7c); 18.66 (4-CH , 6c); 20.72 (CH CH CH CH ,
3 3 3 2 2 2
6c); 21.00 (CH CH CH CH , 7c); 22.84 (CH CH CH CH ,
3 2 2 2 3 2 2 2
7c); 23.91 (6-CH , 6c); 24.27 (6-CH , 7c); 24.34 (CH CH -
3
3
3
2
CH CH , 6c); 50.92 (CH CH CH CH , 7c); 55.46 (CH CH -
15
13
3
2
2
2
3
2
2
2
3
2
–
1
C, 56.41; H, 4.10; N, 4.39; S, 20.08. IR, /cm : 3320 (OH), 3064,
CH CH , 6c); 70.18 (CTP(2), 7c); 110.45 (CTP(2), 6c); 119.67
2 2
2
7
920, 1588, 1560, 1504, 1312 (SO ), 1192, 1144 (SO ), 1124, 820,
(CTP(3a), 7c); 122.53 (CTP(5), 6c); 122.83 (CTP(3a), 6c); 122.97
(CTP(5), 7c); 146.12 (CTP(3), 6c); 151.32 (CTP(4), 7c); 151.88
2
2
1
24, 688. H NMR (CDCl ), : 2.50 (s, 0.6 H, 4-CH , 7a); 2.52
3
3

3
64
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 2, February, 2019
Kalugin and Shestopalov
(
(
CTP(4), 6c); 158.02 (CTP(7a), 6c); 159.90 (CTP(6), 6c); 166.34
CTP(6), 7c); 172.20 (CTP(7a), 7c); 190.67 (CTP(3), 7c).
orless crystals, m.p. 158—160 C (MeOH). Found (%): C, 56.67;
H, 4.48; N, 8.75; S, 20.05. C H N O S . Calculated (%):
15
14
2
2 2
–
1
4
,6-Dimethyl-2-(morpholin-4-ylsulfonyl)thieno[2,3-b]pyri-
C, 56.58; H, 4.43; N, 8.80; S, 20.14. IR, /cm : 3062, 2998,
2927, 2218 (CN), 1585, 1543, 1448, 1305 (SO ), 1271, 1152 (SO ),
1083, 871, 771, 719, 701, 580. H NMR (CDCl ), : 2.41 (s, 3 H,
4-CH ); 2.43 (s, 3 H, 6-CH ); 5.04 (s, 2 H, SCH SO ); 6.79
dine-3-ol (6d) and 4,6-dimethyl-2-(morpholin-4-ylsulfonyl)-
thieno[2,3-b]pyridin-3(2H)-one (7d) (6d : 7d = 90 : 10). The yield
was 0.43 g (43%), pink crystals, m.p. 148—150 C (MeOH).
Found (%): C, 47.37; H, 5.02; N, 8.41; S, 19.61. C H N O S .
Calculated (%): C, 47.55; H, 4.91; N, 8.53; S, 19.52. IR, /cm
3
1
8
2
2
1
3
3
3
2
2
(s, 1 H, HPy(5)); 7.42—7.58 (m, 3 H, HPhSO2(3), HPhSO2(4),
H (5) Ph); 7.70—7.80 (m, 2 H, HPhSO2(2), HPhSO2(6)).
PhSO
13
16
2
4
2
1
–
:
2
13
337 (OH), 2967, 2924, 2856, 1704 (C=O), 1587, 1567, 1509,
C NMR (DMSO-d ), : 19.45 (4-CH ); 23.94 (6-CH ); 51.17
6 3 3
449, 1346, 1331 (SO ), 1262, 1199, 1153 (SO ), 1070, 1017, 939,
(SCH SO ); 104.49 (CPy(3)); 114.36 (CN); 121.54 (CPy(5));
2 2
2
2
1
20, 727. H NMR (CDCl ), : 2.59 (s, 0.3 H, 4-CH , 7d); 2.60
128.55 (CPhSO2(3), CPhSO2(5)); 128.81 (CPhSO2(2), CPhSO2(6));
134.01 (CPhSO2(4)); 137.18 (CPhSO2(1)); 152.77 (CPy(4)); 155.36
(CPy(2)); 161.27 (CPy(6)).
3
3
(
s, 0.3 H, 6-CH , 7d); 2.65 (s, 2.7 H, 4-CH , 6d); 2.73 (s, 2.7
3
3
H, 6-CH , 6d); 3.23 (t, 3.6 H, CH NCH , J = 4.4 Hz, 6d);
3
2
2
3
.43—3.53 (m, 0.4 H, CH NCH , 7d); 3.63—3.70 (m, 0.4 H,
The similar reaction of pyridinthione 1a (0.66 g, 4 mmol)
and chloromethyl benzyl sulfone 2b (0.82 g, 4 mmol) with sodium
methoxide (0.25 mg, 4.6 mmol) in anhydrous DMF (10 mL) gave
a mixture of initial sulfone 2b (0.33 g, 1.61 mmol) and 2-{[(benz-
ylsulfonyl)methyl]thio}-4,6-dimethylpyridine-3-carbonitrile 8b
(0.47 g, 1.41 mmol), colorless crystals, m.p. 150—152 C (MeOH).
2
2
CH OCH , 7d); 3.80 (t, 3.6 H, CH OCH , J = 4.4 Hz, 6d); 5.17
2
2
2
2
(
s, 0.1 H, HTP(2), 7d); 6.88 (s, 0.1 H, HTP(5), 7d); 7.03 (s, 0.9
13
H, HTP(5), 6d); 9.01 (br.s, 0.9 H, 3-OH, 6d). C NMR
(
(
(
6
DMSO-d ), : 17.59 (4-CH , 7d); 18.72 (4-CH , 6d); 23.91
6
3
3
6-CH , 6d); 24.27 (6-CH , 7d); 45.92 (CH NCH , 6d); 46.62
3
3
2
2
CH NCH , 7d); 65.27 (CH OCH , 6d); 66.05 (CH OCH , 7d);
Found (%): C, 57.73; H, 4.91; N, 8.35; S, 19.22. C H N O S .
2
2
2
2
2
2
16 16
2
2
2
1
–
9.45 (CTP(2), 7d); 105.70 (CTP(2), 6d); 120.04 (CTP(3a), 7d);
22.47 (CTP(5), 7d); 122.58 (CTP(5), 6d); 122.90 (CTP(3a), 6d);
45.98 (CTP(3), 6d); 151.77 (CTP(4), 6d); 151.87 (CTP(4), 7d);
57.39 (CTP(7a), 6d); 159.78 (CTP(6), 6d); 166.27 (CTP(6), 7d);
71.93 (CTP(7a), 7d); 190.14 (CTP(3), 7d).
-Hydroxy-4,6-dimethyl-N-phenylthieno[2,3-b]pyridine-2-
Calculated (%): C, 57.81; H, 4.85; N, 8.43; S, 19.29. IR, /cm
:
1
2996, 2918, 2216 (CN), 1583, 1356, 1302 (SO ), 1122 (SO ), 776, 693.
2 2
1
1
H NMR (CDCl ), : 2.51 (s, 3 H, 4-CH ); 2.53 (s, 3 H, 6-CH );
3 3 3
1
4.41 (s, 2 H, PhCH ); 4.81 (s, 2 H, SCH SO ); 6.94 (s, 1 H, HPy(5));
2 2 2
13
1
7.38—7.46 (m, 5 H, Ph). C NMR (DMSO-d ), : 19.62 (4-CH );
6 3
3
24.09 (6-CH ); 48.00 (PhCH ); 57.39 (SCH SO ); 104.53
3 2 2 2
sulfonamide (6e) and 4,6-dimethyl-3-oxo-N-phenyl-2,3-dihydro-
thieno[2,3-b]pyridine-2-sulfonamide (7e) (6e : 7e = 40 : 60). The
yield was 0.48 g (48%), light porcelain crystals, m.p. 182—184 C
(CPy(3)); 114.56 (CN); 121.73 (CPy(5)); 127.91 (CBnSO2(1));
128.47 (CBnSO2(3), CBnSO2(4), CBnSO2(5)); 131.11 (CBnSO2(2),
CBnSO2(6)); 153.12 (CPy(4)); 156.10 (CPy(2)); 161.51 (CPy(6)).
(
MeOH). Found (%): C, 54.06; H, 4.31; N, 8.21; S, 19.29.
C H N O S . Calculated (%): C, 53.88; H, 4.22; N, 8.38;
1
5
14
2
3
2
References
–
1
S, 19.17. IR, /cm : 3455 (NH), 3294 (OH), 3012, 2868, 2800,
2
697, 1728 (C=O), 1592, 1584, 1516, 1493, 1318 (SO ), 1222,
2
1. Pat. WO 2007072095; Chem. Abstr., 2007, 147, 118206.
2. K. Nogradi, G. Wagner, G. Domami, A. A. Bobok, I. Magdo,
S. Kolok, M. L. Miko-Bakk, M. Vastag, K. Saghy, I. Gyertian,
J. Koti, K. Gal, S. Faras, G, M, Keserue, I. Greiner,
Z. Szombachcliy, Bioorg. & Med. Chem. Lett., 2015, 25, 1724.
3. V. E. Kalugin, A. M. Shestopalov, V. P. Litvinov, Russ. Chem.
Bull., 2006, 55, 529.
4. K. Gewald, M. Hentschel, U. Illgen, J. Pract. Chem., 1974,
316, 1030.
5. L. A. Rodinovskaya, E. V. Belukhina, A. M. Shestopalov,
V. P. Litvinov, Russ. Chem. Bull., 1994, 43, 489.
6. A. A. Krause, Z. A. Bomina, A. M. Shestopalov, L. A.
Rodinovskaya, Yu. E. Pelcher, G. Ya. Dubur, Yu. A. Sharanin,
V. K. Promonenkov, Chem. Heterocycl. Compd., 1981, 17, 279.
7. 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.
1
202, 1142 (SO ), 1114, 1015, 943, 819, 755, 696, 647, 592.
2
1
H NMR (CDCl ), : 2.58 (s, 3.6 H, 4,6-CH , 7e); 2.63 (s, 1.2 H,
3
3
4
7
7
-CH , 6e); 2.65 (s, 1.2 H, 6-CH , 6e); 5.07 (s, 0.6 H, HTP(2),
3
3
e); 6.87 (s, 0.6 H, HTP(5), 7e); 6.98 (s, 0.4H, HTP(5), 6e);
.10—7.21 (m, 2 H, HPhN(2), HPhN(6)); 7.24—7.31 (m, 2 H, NH
and HPhN(4)); 7.36—7.50 (m, 2 H, HPhN(3), HPhN(5)); 8.90
13
(
br.s, 0.4 H, 3-OH, 6e). C NMR (DMSO-d ), : 17.47 (4-CH ,
6 3
7
6
e); 18.63 (4-CH , 6e); 23.87 (6-CH , 6e); 24.25 (6-CH , 7e);
3 3 3
9.21 (CTP(2), 7e); 109.47 (CTP(2), 6e); 119.61 (CTP(3a), 7e);
1
20.19 (CPhN(2), CPhN(6), 6e); 120.90 (CPhN(2), CPhN(6), 7e);
22.04 (CTP(3a), 6e); 122.46 (CTP(5), 6e); 122.71 (CTP(5), 7e);
24.48 (CPhN(4), 6e); 124.65 (CPhN(4), 7e); 129.08 (CPhN(3),
1
1
CPhN(5), 7e); 129.22 (CPhN(3), CPhN(5), 6e); 136.85 (CPhN(1),
6
7
1
e); 137.13 (CPhN(1), 7e); 145.80 (CTP(3), 6e); 150.82 (CTP(4),
e); 151.11 (CTP(4), 6e); 157.39 (CTP(7a), 6e); 159.65 (CTP(6), 6e);
65.89 (CTP(6), 7e); 171.52 (CTP(7a), 7e); 189.14 (CTP(3), 7e).
The reaction of 4,6-dimethyl-3-cyanopyridine-2-thione (1a)
with chloromethyl organyl sulfones 2a,b using sodium methoxide
as the base. Sodium methoxide (320 mg, 5.7 mmol) was added
to a solution of pyridinethione 1a (0.82 g, 5 mmol) and chloro-
methyl phenyl sulfone 2a (0.95 g, 5 mmol) in anhydrous DMF
8
. V. D. Dyachenko, S. G. Krivikolysko, V. N. Nesterov, V. P.
Litvinov, Chem. Heterocycl. Compd., 1996, 32, 1066.
. F. A. Abu-Shanab, A. D. Redhouse, J. R. Tompson, B. J.
Wakefield, Synthesis, 1995, 557.
9
1
0. L. W. Cristensen, J. M. Seamen, W. E. Truce, J. Org. Chem.,
(
12 mL). The reaction mixture was heated at 120—125 C for 2 h,
1973, 38, 2243.
cooled to room temperature, and diluted with CH Cl (30 mL).
2
2
11. G. E. H. Elgemeie, H. A. Elfahham, H. A. Nabey, Bull. Soc.
Chim. Jpn, 1988, 61, 4431.
12. Z. El-Hewehi, F. Runge, J. Pract. Chem., 1962, 16, 297.
The resulting solution was filtered from resinous substances,
washed with H O (3×30 mL), and dried over MgSO . The solvent
2
4
was evaporated, and the products were isolated by chromato-
1
3. V. E. Kalugin, A. M. Shestopalov, Russ. Chem. Bull., 2008,
graphy on silica gel. The eluent was hexane—CHCl3 mixture
57, 2139.
(
2 : 1 and 3 : 2). The evaporation of fractions gave initial sulfone
a (0.46 g, 2.41 mmol) and 4,6-dimethyl-2-{[(phenylsulfonyl)
methyl]thio}pyridine-3-carbonitrile 8a (0.38 g, 1.2 mmol), col-
Received July 27, 2018;
in revised form November 16, 2018;
accepted November 26, 2018
2