Synthesis and properties of 4-(3-aminothieno-[2,3-b]pyridin-2-yl)coumarins

Article abstract of DOI:10.1007/s10593-012-1083-2

Substituted 4-[(3-cyanopyridin-2-yl)thiomethyl]coumarins have been synthesized by the alkylation of 2-mercapto-4,6-dimethylnicotinonitrile with 4-chloromethylcoumarins. Substituted 4-(3-amino-thieno[2,3-b]pyridin-2-yl) coumarins have been obtained by a subsequent intramolecular condensation of the methylene and cyano groups. 6H-Chromeno[4,3-d]thieno[3,2-b:5,4-b']dipyridin-6- ones were isolated as a result of the interaction of these compounds with aldehydes, and their aminomethyl derivatives were synthesized.

Full text of DOI:10.1007/s10593-012-1083-2

Chemistry of Heterocyclic Compounds, Vol. 48, No. 6, September, 2012 (Russian Original Vol. 48, No. 6, June, 2012)
SYNTHESIS AND PROPERTIES OF 4-(3-AMINOTHIENO-
[2,3-b]PYRIDIN-2-YL)COUMARINS
S. V. Gorelov1, S. P. Bondarenko2, and M. S. Frasinyuk3*
Substituted 4-[(3-cyanopyridin-2-yl)thiomethyl]coumarins have been synthesized by the alkylation of
2-mercapto-4,6-dimethylnicotinonitrile with 4-chloromethylcoumarins. Substituted 4-(3-amino-
thieno[2,3-b]pyridin-2-yl)coumarins have been obtained by a subsequent intramolecular condensation
of the methylene and cyano groups. 6H-Chromeno[4,3-d]thieno[3,2-b:5,4-b']dipyridin-6-ones were
isolated as a result of the interaction of these compounds with aldehydes, and their aminomethyl
derivatives were synthesized.
Keywords: 4-chloromethylcoumarin, 5H-chromeno[3,4-c]pyridin-5-one, 6H-chromeno[4,3-d]thieno-
[3,2-b:5,4-b']dipyridin-6-one, 1,2-dihydropyridine, 4-(thieno[2,3-b]pyridin-2-yl)coumarin, aminomethyla-
tion.
Natural 4-arylcoumarins (neoflavones) [1-3], as also their synthetic analogs, 4-hetarylcoumarins,
display various types of biological activity [4, 5]. In particular, recent investigations of the biological properties
of 4-pyridylcoumarins revealed among them compounds with high anticancer [6], anti-inflammatory, analgesic,
and antimicrobial [7] activity. In view of these circumstances, the search for synthetic routes towards new
pyridine-containing coumarins seemed of interest.
In addition to the main methods of 4-arylcoumarin synthesis [8], the cross-coupling of
4-trifluoromethanesulfonyloxycoumarins and 4-tosyloxycoumarins with (het)arylboronic acids or their pinacol
esters [4, 5, 9], and also with hetaryl organometallic compounds [10, 11], is increasingly used at the present
time.
4-Chloromethylcoumarin derivatives are convenient intermediates for introduction of a hetaryl
substituent into the position 4 of the coumarin system. Recently, using 4-chloromethylcoumarins and the (7-hydr-
oxy-2-oxo-2H-chromen-4-yl)acetic acid methyl ester, we improved the synthesis of 4-(2-benzofuryl)coumarins
[12] and 4-(2-oxo-2H-chromen-3-yl)coumarins [13], respectively.
In the present study, we have used 4-chloromethylcoumarins for the synthesis of 4-(thieno[2,3-b]pyri-
din-2-yl)coumarin derivatives by the alkylation of 2-mercapto-4,6-dimethylnicotinonitrile (see [6]).
_______
*To whom correspondence should be addressed, e-mail: horelovs@ukr.net.
1PJSC SIC "Borshchahivskiy Chemical Pharmaceutical Plant", 17 Mira St., Kyiv 03134, Ukraine.
2National University of Food Technology, 68 Volodyimirska St., Kyiv 01601, Ukraine; e-mail:
sp_bondarenko@ukrpost.ua.
3Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 1
Murmanska St., Kyiv 02094, Ukraine; e-mail: mfras@i.kiev.ua.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 1026-1033, June, 2012. Original
article submitted August 18, 2011.
0009-3122/12/4806-0955©2012 Springer Science+Business Media New York
955

Me
N
O
O
O
NC
S
Me
5'
Cl
3'
1O
N
H
Me
4
K2CO3
S
DMF
80-100°C
8
R2
N
R2
Et3N, EtOH
1'
6
Me
R1
R
R
R1
2a–h
1a–h
4''
Me
2''
H2N
O
(from 3b,d,f,g)
Me
3'
N
O
5'
1O
OMe
MeO
O
4
1O
S
N
Me
AcOH
90-100°C
1'
R2
S
N
Me
8
R2
6
R1
R
3a–h
R1
R
4a–d
1–3 a R = Me, R1 = R2 = H; 1–3 b, 4a R+R1 = (CH2)3, R2 = H; 1–3 c R = OH, R1 = R2 = H;
1–3 d, 4b R = OH, R1 = Me, R2 = H; 1–3 e R = OH, R1 = Ph, R2 = H; 1–3 f, 4c R = Cl, R1 = OH, R2 = H;
1–3 g, 4d R = Et, R1 = OH, R2 = H; 1–3 h R = H, R1 = OH, R2 = Me
Choice of the latter enabled the use of 4-chloromethylcoumarins containing phenolic hydroxyl groups as
alkylating agents, since the significant difference in nucleophilicity of the mercapto group and phenolic
hydroxyl directed the course of the reaction exclusively to the sulfur atom.
We found that the 4-chloromethylcoumarins 1a-h interact with 2-mercapto-4,6-dimethylnicotinonitrile
in alcohol in the presence of triethylamine at room temperature with the formation of 4-(2-pyridylthio-
methyl)coumarins 2a-h (Tables 1, 2).
The intramolecular cyclization of the methylene and cyano groups in 4-(2-pyridylthiomethyl)coumarins
2a-h was carried out in DMF under the action of potassium carbonate that led to the formation of substituted
4-(3-aminothieno[2,3-b]pyridin-2-yl)coumarins 3a-h. The synthesized compounds 3a-h were high-melting
yellow substances, sparingly soluble in organic solvents and readily soluble in aqueous solutions of mineral
acids and alkali.
1
The presence of amino groups in compounds 3a-h was demonstrated by H NMR spectroscopy. For
1
instance, a two-proton broadened singlet was observed in the 5.08-5.24 ppm region of the H NMR spectra of
the synthesized substituted coumarins 3a-h, which corresponds to the amino group (Table 2).
One of the interesting routes for modification of the amino group, in our view, is the construction of a
pyrrole ring with the aid of 2,5-dimethoxytetrahydrofuran. We found that brief heating of amines 3b,d,f,g with
this reagent in acetic acid led to the formation of 1-(thieno[2,3-b]pyridin-3-yl)pyrroles 4a-d.
It was shown previously in [7, 12], that 4-(3-aminobenzofuran-2-yl)coumarins are convenient starting
materials for the construction of the pyrido[3,4-c]coumarin system, which is a structural fragment of alkaloids
isolated from Schumanniophyton problematicum [14]. At this time various methods for the synthesis of
5H-chromeno[3,4-c]pyridin-5-one derivatives have been developed (see literature review in [12]).
As it turned out, the interaction of compounds 3a,c,g,h with aliphatic or aromatic aldehydes in formic
acid with subsequent oxidation of the intermediate products 5a,b,d-f with diacetoxyiodosobenzene enabled the
preparation of derivatives 6a,b,d-f of a new condensed system, 6H-chromeno[4,3-d]thieno[3,2-b:5,4-b']dipyri-
din-6-one. In the case of the synthesis of compound 6c it proved to be expedient to use triethyl orthoformate
[7]. We propose that, as in the case of derivatives of 6H-[1]benzofuro[3,2-b]chromeno[4,3-d]pyridin-6-ones
[12], the synthesis of compounds 6a,b,d-f proceeds through the sequential generation of a Schiff base, its
intramolecular cycloaddition with the formation of condensed 1,2-dihydropyridines 5a,b,d-f, and oxidation of
the latter to pyridine derivatives.
956

TABLE 1. Physicochemical Characteristics of Coumarin Derivatives 1f,g,
2a-h, 3a-h, 4a-d, 6a-f, 7a-c
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
Mp, °С
Yield, %
C
H
N
S
C10H6Cl2O3
49.17
49.01
60.28
60.39
67.65
67.84
69.67
69.59
63.76
63.89
64.85
64.76
69.47
69.55
58.12
57.99
65.35
65.56
64.94
64.76
67.65
67.84
69.78
69.59
63.99
63.89
64.57
64.76
69.38
69.55
58.07
57.99
65.80
65.56
64.59
64.76
72.92
72.79
68.46
68.64
62.75
62.49
69.35
69.21
75.46
75.29
68.92
68.71
66.89
67.01
67.81
67.67
69.82
69.69
67.39
67.46
66.64
66.49
65.92
65.67
69.14
68.97
2.58
2.47
4.53
4.65
4.86
4.79
5.12
5.01
3.99
4.17
4.46
4.58
4.25
4.38
3.64
3.51
5.07
4.95
4.47
4.58
4.89
4.79
5.13
5.01
4.28
4.17
4.80
4.58
4.49
4.38
3.67
3.51
4.87
4.95
4.80
4.58
4.75
4.89
4.47
4.51
3.73
3.58
4.90
4.84
5.63
5.48
3.87
3.99
4.24
4.28
4.59
4.65
4.73
4.60
4.59
4.45
5.18
5.35
5.35
5.30
6.11
5.99
271-272
219-220
220-221
248-250
265-266
285-287
270-271
262-264
241-242
274-275
208-210
226-228
>300
56
72
80
77
81
79
75
82
75
83
76
69
71
75
79
76
73
75
46
58
57
62
63
48
65
38
45
56
76
58
61
1f
C12H11ClO3
1g
2a
2b
2c
2d
2e
2f
C19H16N2O2S
C21H18N2O2S
C18H14N2O3S
C19H16N2O3S
C24H18N2O3S
C18H13ClN2O3S
C20H18N2O3S
C19H16N2O3S
C19H16N2O2S
C21H18N2O2S
C18H14N2O3S
C19H16N2O3S
C24H18N2O3S
C18H13ClN2O3S
C20H18N2O3S
C19H16N2O3S
C25H20N2O2S
C23H18N2O3S
C22H15ClN2O3S
C24H20N2O3S
C30H26N2O2S
C26H18N2O4S
C21H16N2O3S
C22H18N2O3S
C28H22N2O4S
C28H22N2O5S
C24H23N3O3S
C26H25N3O4S
C28H29N3O3S
8.47
8.33
7.81
7.73
8.16
8.28
7.77
7.95
6.85
6.76
7.38
7.51
7.72
7.64
7.72
7.95
8.45
8.33
7.65
7.73
8.41
8.28
8.14
7.95
6.87
6.76
7.29
7.51
7.75
7.64
8.14
7.95
6.91
6.79
6.83
6.96
6.50
6.62
6.51
6.73
5.73
5.85
6.28
6.16
7.65
7.44
7.37
7.17
5.63
5.81
5.81
5.62
9.79
9.69
8.72
8.84
9.41
9.53
8.93
8.85
9.56
9.48
9.22
9.10
7.82
7.74
8.71
8.60
8.63
8.75
9.25
9.10
9.41
9.53
8.67
8.85
9.39
9.48
9.22
9.10
7.67
7.74
8.47
8.60
8.64
8.75
9.02
9.10
7.85
7.77
8.05
7.97
7.68
7.58
7.88
7.70
6.58
6.70
6.87
7.05
8.33
8.52
8.44
8.21
6.54
6.64
6.32
6.43
7.59
7.40
6.82
6.74
2g
2h
3a
3b
3c
3d
3e
3f
>300
>300
186-187
259-260
>300
3g
3h
4а
4b
4c
4d
6a
6b
6c
6d
6e
6f
237-239
275-276
274-275
>300
301
>300
>300
288-290
>300
>300
>300
7a
7b
7c
275-277
261-262
8.50
8.62
6.68
6.58
957

R3
R3
O
O
H
N
N 8
O
N
6
O
R
R2
R1
Me
R2
R1
Me
PhI(OAc)2
60–70°C
4
10
S
5a,b,d–f
S
6a,b,d–f
1
N
R
Me
Me
HCOOH
40–50°C
R3CHO
3a,c,g,h
HC(OEt)3
110–120°C
(from 3g)
O
O
O
N
O
N
(R4R5N)2CH2
Me
Me
R4R5N
HO
Dioxane, 
S
S
HO
N
N
Et
Et
Me
Me
7a–c
6c
6 a R = Me, R1 = R2 = H, R3 = 4-(t-Bu)C6H4; b R = OH, R1 = R2 = H, R3 = 4-MeOC6H4;
d R = Et, R1 = OH, R2 = H, R3 = Me; e R = Et, R1 = OH, R2 = H, R3 = 4-MeOC6H4;
f R = H, R1 = OH, R2 = Me, R3 = 3,4-(MeO)2C6H3;
7 a R4 = R5 = Me, b R4+R5 = CH2CH2OCH2CH2, c R4+R5 = CH2CH2CH(Me)CH2CH2
The synthesized polycyclic compounds 6a-f are high-melting crystalline substances, poorly soluble in
organic solvents.
On heating compound 6c with aminals in dioxane, aminomethylation occurs with the formation of
Mannich bases 7a-c, which are readily soluble in organic solvents and in dilute solutions of mineral acids.
Therefore, it has been shown by us that 4-(3-aminohetaryl)coumarins may be convenient starting
materials for the synthesis of condensed polycyclic derivatives of 5H-chromeno[3,4-c]pyridin-5-one.
Derivatives of a new heterocyclic system, 6H-chromeno[4,3-d]thieno[3,2-b:5,4-b']dipyridin-6-one, have been
synthesized by the interaction of 4-(3-aminothieno[2,3-b]pyridin-2-yl)coumarins with aldehydes, followed by
intramolecular cyclization and oxidation. Aminomethylation of these compounds under the action of aminals
has been studied.
EXPERIMENTAL
1
The IR spectra were recorded on a Nicolet 380 FT-IR in KBr pellets. The H NMR spectra were
recorded on a Varian VXR 300 spectrometer at 300 MHz, internal standard was TMS. Melting points were
determined on a Buchi B-535 instrument. A check on the progress of reactions and the purity of the obtained
compounds was carried out by TLC on Merck 60 F254 plates, the eluent was CHCl3–MeOH, 9:1, 19:1.
Compounds 1a-e,h were synthesized by the procedures of [15-17].
6-Chloro-4-chloromethyl-7-hydroxy-2H-chromen-2-one (1f) and 4-Chloromethyl-6-ethyl-7-hydr-
oxy-2H-chromen-2-one (1g). A mixture of 4-chloroacetoacetic ester (16.46 g, 0.1 mol) and the 2-substituted
resorcinol (0.1 mol) was poured into 73% H2SO4 (50 ml) and stirred for 18-24 h at room temperature. The
reaction mixture was poured onto ice, the precipitated solid was filtered off, washed with water, and crystallized
from MeOH.
958

TABLE 2. Spectral Characteristics of the Synthesized Compounds 1f,g,
2a-h, 3a-h, 4a-d, 6a-f, 7a-c
Com-
pound
1
IR spectrum,
1H NMR spectrum, , ppm (J, Hz)*
, cm-1
2
3
3288, 1707,
5.00 (2Н, s, CH2Cl); 6.49 (1H, s, Н-3); 6.94 (1Н, s, H-8);
1f
1614, 1398, 640 7.86 (1H, s, H-5); 11.51 (1Н, s, 7-OH)
3270, 1716,
1.20 (3Н, t, 3J = 7.4, CH2CH3); 2.62 (2Н, q, 3J = 7.4, CH2CH3);
1g
4.83 (2H, s, CH2Cl); 6.29 (1H, s, Н-3); 6.74 (1Н, s, H-8);
7.42 (1H, s, H-5); 10.30 (1Н, br. s, 7-OH)
1618, 1392, 892
2216, 1716,
2.39 (6Н, s) and 2.49 (3H, s, 6,4',6'-CH3); 4.74 (2Н, s, CH2S);
6.59 (1H, s, Н-3); 7.15 (1Н, s, H-5'); 7.31 (1H, d, 3J = 8.4, H-8);
7.46 (1Н, dd, 3J = 8.4, 4J = 1.8, H-7); 7.80 (1H, d, 4J = 1.8, H-5)
2a
2b
1621, 1575, 1543
2217, 1708,
1.98-2.15 (2Н, m, CH2CH2CH2); 2.39 (3Н, s) and
2.49 (3Н, s, 4',6'-CH3); 2.88-3.00 (4Н, m, CH2CH2CH2);
4.72 (2Н, s, CH2S); 6.50 (1H, s, Н-3); 7.14 (1Н, s, H-5');
7.25 (1H, s, H-8); 7.80 (1H, s, H-5)
1618, 1581, 1556
3185, 2216,
1677, 1417
2.40 (3Н, s) and 2.50 (3H, s, 4',6'-CH3); 4.70 (2Н, s, CH2S);
6.58 (1H, s, Н-3); 7.08 (1Н, dd, 3J = 8.9, 4J = 1.7, H-7);
7.16 (1Н, s, H-5'); 7.24 (1H, d, 4J = 1.7, H-5);
2c
7.28 (1H, d, 3J = 8.9, H-8); 9.82 (1Н, s, OH)
3187, 2217,
2.23 (3Н, s, 7-CH3); 2.40 (3H, s) and 2.50 (3H, s, 4',6'-CH3);
4.64 (2Н, s, CH2S); 6.50 (1H, s, Н-3); 7.15 (1H, s), 7.16 (1H, s) and
7.19 (1H, s, H-5,5',8); 9.72 (1Н, s, OH)
2d
2e
2f
1678, 1579, 1416
3193, 2220,
1678, 1579, 1411
2.41 (3Н, s) and 2.51 (3H, s, 4',6'-CH3); 4.70 (2Н, s, CH2S);
6.60 (1H, s, Н-3); 7.17 (1Н, s, H-5'); 7.35 (2H, s, H-5,8);
7.36-7.47 (3Н, m) and 7.62-7.68 (2Н, m, Н Ph); 10.00 (1Н, s, OH)
3245, 2222,
2.39 (3Н, s) and 2.49 (3H, s, 4',6'-CH3); 4.70 (2Н, s, CH2S);
1716, 1599, 1585 6.43 (1H, s, Н-3); 6.91 (1H, s, H-8); 7.16 (1Н, s, H-5');
8.06 (1H, s, H-5); 11.47 (1Н, s, OH)
3238, 2218,
1.12 (3Н, t, 3J = 7.5, CH2CH3); 2.40 (3H, s) and 2.50 (3H, s, 4',6'-CH3);
2g
1679, 1605, 1384 2.56 (2Н, q, 3J = 7.5, CH2CH3); 4.72 (2Н, s, CH2S); 6.34 (1H, s, Н-3);
6.77 (1H, s, H-8); 7.14 (1Н, s, H-5'); 7.61 (1H, s, H-5);
10.61 (1H, s, OH)
3178, 2218,
2.16 (3H, s, 8-CH3); 2.39 (3Н, s) and 2.49 (3H, s, 4',6'-CH3);
2h
3a
1678, 1605, 1573 4.67 (2Н, s, CH2S); 6.34 (1H, s, Н-3); 6.89 (1Н, d, 3J = 8.8, H-6);
7.13 (1Н, s, H-5'); 7.63 (1H, d, 3J = 8.8, H-5); 10.44 (1Н, s, OH)
3413, 1712,
1699, 1560
2.34 (3Н, s, 6-CH3); 2.53 (3Н, s) and 2.77 (3H, s, 4',6'-CH3);
5.21 (2Н, s, NH2); 6.48 (1H, s, Н-3); 7.08 (1Н, s, H-5');
7.38 (1H, d, 3J = 8.6, H-8); 7.47 (1Н, dd, 3J = 8.6, 4J = 1.8, H-7);
7.51 (1H, d, 4J = 1.8, H-5)
3411, 1709,
1621, 1548
1.99-2.11 (2Н, m, CH2CH2CH2); 2.52 (3Н, s) and
2.77 (3H, s, 4',6'-CH3); 2.82-3.00 (4Н, m, CH2CH2CH2);
5.16 (2Н, s, NH2); 6.40 (1H, s, Н-3); 7.07 (1Н, s, H-5');
7.34 (1H, s, H-8); 7.50 (1H, s, H-5)
3b
3463, 1673,
2.53 (3Н, s) and 2.77 (3H, s, 4',6'-CH3); 5.20 (2Н, s, NH2);
3c
3d
3e
1562, 1446, 1230 6.46 (1H, s, Н-3); 6.98-7.13 (3H, m, H-5,5',7);
7.32 (1H, d, 3J = 8.4, H-8); 9.65 (1Н, s, OH)
3442, 1659,
2.23 (3Н, s, 7-CH3); 2.53 (3Н, s) and 2.77 (3H, s, 4',6'-CH3);
1618, 1444, 1411 5.17 (2Н, s, NH2); 6.39 (1H, s, Н-3); 7.07 (1Н, s, H-5');
7.12 (1H, s, H-5); 7.24 (1H, s, H-8); 9.60 (1Н, s, 6-OH)
3398, 1710,
2.53 (3Н, s) and 2.79 (3H, s, 4',6'-CH3); 5.24 (2Н, s, NH2);
1562, 1413, 1286 6.49 (1H, s, Н-3); 7.08 (1Н, s, H-5'); 7.30 (1H, s, H-5);
7.34-7.49 (3Н, m, Н Ph); 7.62-7.68 (2Н, m, Н Ph);
7.40 (1H, s, H-8); 9.83 (1Н, s, OH)
3465, 1701,
2.52 (3Н, s) and 2.79 (3Н, s, 4',6'-CH3); 5.21 (2Н, s, NH2);
3f
1608, 1448, 1365 6.40 (1H, s, Н-3); 6.85 (1H, s, H-8); 7.08 (1Н, s, H-5');
7.35 (1H, s, H-5); 11.52 (1Н, s, OH)
3482, 2915,
1.10 (3Н, t, 3J = 7.5, CH2CH3); 2.53 (3Н, s) and 2.77 (3Н, s, 4',6'-CH3);
3g
1697, 1614, 1369 2.57 (2Н, q, 3J = 7.5, CH2CH3); 5.17 (2Н, s, NH2); 6.21 (1H, s, Н-3);
6.82 (1H, s, H-8); 7.08 (1Н, s, H-5'); 7.46 (1H, s, H-5); 10.66 (1Н, s, OH)
959

TABLE 2 (continued)
1
2
3
3411, 1706,
2.21 (3Н, s, 8-CH3); 2.52 (3Н, s) and 2.76 (3Н, s, 4',6'-CH3);
3h
1605, 1562, 1369 5.08 (2Н, s, NH2); 6.21 (1H, s, Н-3); 6.84 (1H, d, 3J = 8.8, H-6);
7.06 (1Н, s, H-5'); 7.40 (1H, d, 3J = 8.8, H-5); 10.52 (1Н, s, OH)
1708, 1618,
1548, 1421
1.92 (3H, s, 4'-CH3); 1.98-2.10 (2H, m, CH2CH2CH2);
2.59 (3Н, s, 6'-CH3); 2.80-2.99 (4H, m, CH2CH2CH2);
6.07-6.13 (2H, m, H-2'',5''); 6.53 (1H, s, Н-3);
6.90-6.96 (2H, m, H-3'',4''); 7.22 (1Н, s, H-5');
7.26 (1Н, s, H-8); 7.43 (1H, s, H-5)
4a
1685, 1560,
1415, 1211
1.91 (3H, s, 4'-CH3); 2.20 (3Н, s, 7-CH3); 2.60 (3Н, s, 6'-CH3);
6.12-6.16 (2H, m, H-2'',5''); 6.53 (1H, s, Н-3); 6.88-6.92 (2H, m, H-3'',4'');
6.96 (1H, s, H-5); 7.20 (1Н, s, H-5'); 7.25 (1Н, s, H-8); 9.60 (1H, s, OH)
4b
4c
4d
3434, 1726,
1600, 1357
1.92 (3H, s, 4'-CH3); 2.60 (3Н, s, 6'-CH3); 6.09-6.13 (2H, m, H-2'',5'');
6.44 (1H, s, Н-3); 6.91 (1Н, s, H-8); 6.96-7.00 (2H, m, H-3'',4'');
7.23 (1Н, s, H-5'); 7.58 (1H, s, H-5); 11.58 (1Н, s, OH)
1.06 (3H, t, 3J = 7.4, CH2CH3); 1.92 (3H, s, 4'-CH3);
3446, 1728,
1618, 1357, 1272 2.53 (2H, q, 3J = 7.4, CH2CH3); 2.59 (3Н, s, 6'-CH3);
6.09-6.12 (2H, m, H-2'',5''); 6.32 (1H, s, Н-3); 6.75 (1Н, s, H-8);
6.94-6.97 (2H, m, H-3'',4''); 7.23 (1Н, s, H-5'); 7.31 (1H, s, H-5);
10.71 (1Н, s, OH)
2960, 1738,
1.38 (9H, s, C(CH3)3); 2.48 (3Н, s, 2-CH3); 2.59 (3Н, s) and
6a
6b
1589, 1537, 1062 2.87 (3H, s, 9,11-CH3); 7.27 (1H, s, H-10); 7.36-7.42 (1Н, m, H-4);
7.48 (2Н, d, 3J = 8.4, H-3',5'); 7.53-7.59 (1H, m, H-3);
7.64 (2Н, d, 3J = 8.4, H-2',6'); 8.07-8.12 (1H, m, H-1)
3437, 1736,
2.45 (3Н, s) and 2.69 (3H, s, 9,11-CH3); 3.86 (3H, s, OСН3);
1540, 1510, 1250 6.98 (2Н, d, 3J = 8.1, H-3',5'); 6.99 (1H, s, H-10);
7.08-7.13 (1H, m, H-3); 7.26-7.30 (1Н, m, H-4);
7.56-7.58 (1H, m, H-1); 7.61 (2Н, d, 3J = 8.1, H-2',6');
10.03 (1Н, s, H-2)
3353, 1666,
1556, 1418
1.00 (3H, t, 3J = 7.6, CH2CH3); 2.24 (3Н, s) and 2.37 (3H, s, 9,11-CH3);
2.52 (2H, q, 3J = 7.6, CH2CH3); 6.32 (1Н, s, H-4); 6.87 (1H, s, H-1);
6.92 (1H, s, H-10); 8.56 (1Н, s, H-7); 10.58 (1H, s, OH)
6c
3430, 1733,
1.11 (3H, t, 3J = 7.6, CH2CH3); 2.42 (3Н, s), 2.49 (3Н, s) and
6d
1693, 1616, 1504 2.59 (3H, s, 7,9,11-CH3); 2.52 (2H, q, 3J = 7.6, CH2CH3);
6.46 (1Н, s, H-4); 6.94 (1H, s, H-10); 7.31 (1H, s, H-1);
10.50 (1H, s, OH)
3431, 1720,
1.30 (3H, t, 3J = 7.6, CH2CH3); 2.59 (3Н, s) and 2.88 (3H, s, 9,11-CH3);
6e
6f
1616, 1500, 1249 2.68 (2H, q, 3J = 7.6, CH2CH3); 3.87 (3H, s, ОСН3); 6.77 (1Н, s, H-4);
7.00 (2Н, d, 3J = 8.1, H-3',5'); 7.21 (1H, s, H-10);
7.58 (2Н, d, 3J = 8.1, H-2',6'); 8.03 (1H, s, H-1); 10.56 (1H, s, OH)
3423, 1742,
1612, 1529,
1496, 1257
1.99 (3Н, s, 4-CH3); 2.50 (3Н, s) and 2.62 (3H, s, 9,11-CH3);
3.73 (3H, s, 3'-OСН3); 3.87 (3H, s, 4'-OСН3); 6.70-6.79 (1Н, m, H-2);
6.94-7.02 (2Н, m, H-2',5'); 7.11-7.18 (1Н, m, H-6'); 7.30 (1H, s, H-10);
7.55-7.57 (1H, m, H-1); 10.58 (1H, s, H-3)
3446, 2964,
1.38 (3H, t, 3J = 7.6, CH2CH3); 2.50 (6H, s, N(CH3)2); 2.71 (3Н, s) and
7a
7b
7c
1730, 1604, 1560 3.08 (3H, s, 9,11-CH3); 2.77 (2H, q, 3J = 7.6, CH2CH3);
4.13 (2H, s, CH2N); 7.15 (1H, s, H-10); 8.17 (1H, s, H-1);
9.52 (1H, s, H-7)
3437, 2962,
1.36 (3H, t, 3J = 7.6, CH2CH3); 2.57-2.87 (9Н, m) and
1738, 1605, 1562 3.06 (3H, s, N(CH2)2, CH2CH3, 9,11-CH3); 3.68-3.97 (4H, m, (СН2)2О);
4.16 (2H, s, CH2N); 7.13 (1H, s, H-10); 8.08 (1H, s, H-1);
9.43 (1H, s, H-7)
3431, 2927,
0.97-1.05 (3Н, m, 4'-CH3); 1.39-1.57 (6Н, m) and
1726, 1601, 1558 1.74-1.84 (2Н, m, CH2CH3, 4'-CH, 3',5'-СН2); 2.29-2.45 (2Н, m) and
3.10-3.15 (2H, m, N(CH2)2); 2.72 (3Н, m) and 3.09 (3H, s, 9,11-CH3);
2.77 (2H, q, 3J = 7.6, CH2CH3); 4.16 (2Н, s, CH2N); 7.16 (1H, s, H-10);
8.17 (1H, s, H-1); 9.52 (1H, s, H-7)
_______
1
*The H NMR spectra of compounds 1f,g, 2a-h, 3a-h, 4a-d, and 6a-f were
recorded in DMSO-d6, and of compounds 7a-c in CDCl3.
960

4,6-Dimethyl-2-{[(2-oxo-2H-chromen-4-yl)methyl]thio}nicotinonitriles 2a-h (General Method). A
mixture of 3-cyano-2-mercapto-2,4-dimethylpyridine (1.64 g, 10 mmol) and Et3N (1.69 ml, 12 mmol) in warm
EtOH (25-30 ml) was added to a solution of 4-chloromethylcoumarin 1a-h (10 mmol) in the minimum volume
of EtOH at 40-50oC. The reaction mixture was stirred at room temperature for 18-24 h, diluted with 5 volumes
of water, the precipitated solid was filtered off, and the residue was crystallized from EtOH.
4-(3-Amino-4,6-dimethylthieno[2,3-b]pyridin-2-yl)-2H-chromen-2-ones 3a-h (General Method).
Anhydrous K2CO3 (0.69 g, 5 mmol) was added to a mixture of coumarin 2a-h (10 mmol) in anhydrous DMF
(20 ml) at 60-80oC. The reaction mixture was stirred for 6-8 h at 80-100oC, filtered while hot, the solvent was
evaporated, and the residue was crystallized from a 1:1 mixture of DMF–MeOH.
4-(4,6-Dimethyl-3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridin-2-yl)-2H-chromen-2-ones 4a-d (General
Method). A mixture of amine 3b,d,f,g (2 mmol), 2,5-dimethoxytetrahydrofuran (0.52 ml, 4 mmol), and glacial
acetic acid (20 ml) was heated at 90-100oC for 10-15 min, cooled, and the solvent was distilled off in vacuum.
The residue was crystallized from MeOH.
9,11-Dimethyl-6H-chromeno[4,3-d]thieno[3,2-b:5,4-b']dipyridin-6-ones 6a,b,d-f (General Method). A
solution of 4-(3-aminothieno[2,3-b]pyridin-2-yl)coumarin 3a,c,g,h (1.5 mmol) and aldehyde (2.0 mmol) in
HCOOH (20 ml) was heated at 40-50oC for 0.5-1 h. Then diacetoxyiodosobenzene (0.8 g, 2.5 mmol) was added
to the red solution, and the mixture was stirred at 60-70oC for 2-3 h. The light-yellow colored mixture was
diluted with cold water, the precipitated solid was filtered off, dried, and crystallized from DMF (compounds
6a,b,e,f) or dioxane (compound 6c).
2-Ethyl-3-hydroxy-9,11-dimethyl-6H-chromeno[4,3-d]thieno[3,2-b:5,4-b']dipyridin-6-one (6c). A
mixture of compound 3g (1.1 g, 3 mmol) and triethyl orthoformate (2 ml, 12 mmol) was heated at 110-120oC
for 6 h, cooled, diluted with MeOH (5 ml), the precipitated solid was filtered off and crystallized from a 1:2
mixture of DMF–MeOH.
4-Aminomethyl-2-ethyl-3-hydroxy-9,11-dimethyl-6H-chromeno[4,3-d]thieno[3,2-b:5.4-b']dipyridin-
6-ones 7a-c (General Method). The corresponding aminal (1.2 mmol) was added to a hot solution of
compound 6c (0.38 g, 1.0 mmol) in dioxane (10 ml), the mixture was refluxed for 3-5 h, then cooled. The
solvent was evaporated in vacuum, and the residue was crystallized from EtOH.
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