Synthesis and transformations of 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines

Article abstract of DOI:10.1023/B:RUCB.0000037855.13096.6e

Reactions of 2,5-dimethoxytetrahydrofuran with 3-aminothieno[2,3-b] pyridines afford a number of substituted 3-(1H-pyrrol-1-yl)thieno[2,3-b] pyridines. The possibility of the reaction and the yield of the product are determined by the character of a subst

Full text of DOI:10.1023/B:RUCB.0000037855.13096.6e

Russian Chemical Bulletin, International Edition, Vol. 53, No. 4, pp. 853—859, April, 2004
853
Synthesis and transformations of 3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieno[2,3ꢀb]pyridines
E. A. Kaigorodova,a A. A. Osipova,a L. D. Konyushkin,b and G. D. Krapivina
ꢀ
aKuban State Technological University,
2 ul. Moskovskaya, 350072 Krasnodar, Russian Federation.
Fax: +7 (861) 57 6592. Eꢀmail: organics@kubstu.ru
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: LeonidK@chemicalꢀblock.com
Reactions of 2,5ꢀdimethoxytetrahydrofuran with 3ꢀaminothieno[2,3ꢀb]pyridines afford a
number of substituted 3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieno[2,3ꢀb]pyridines. The possibility of the reacꢀ
tion and the yield of the product are determined by the character of a substituent in position 2
of thieno[2,3ꢀb]pyridine. The Curtius rearrangement of 2ꢀacylazidoꢀ3(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridines yields 4,5ꢀdihydropyrido[3´,2´:4,5]thieno[2,3ꢀe]pyrrolo[1,2ꢀa]pyrazinꢀ4ꢀ
ones. The molecular and crystal structures of ethyl 4ꢀmethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ
1ꢀyl)thieno[2,3ꢀb]pyridineꢀ2ꢀcarboxylate were determined by Xꢀray diffraction analysis.
Key words: 3ꢀaminothieno[2,3ꢀb]pyridines, 2,5ꢀdimethoxytetrahydrofuran, 3ꢀ(1Hꢀpyrrolꢀ
1ꢀyl)thieno[2,3ꢀb]pyridines, 4,5ꢀdihydropyrido[3´,2´:4,5]thieno[2,3ꢀe]pyrrolo[1,2ꢀa]pyrazinꢀ
4ꢀones, IR spectroscopy, UV spectroscopy, 1H NMR spectroscopy, 13C NMR spectroscopy,
Xꢀray diffraction analysis.
Scheme 1
In recent years, the potentialities of the synthesis of
conjugated and fused compounds containing a thieꢀ
no[2,3ꢀb]pyridine fragment have been under extensive
investigations.1—3 Earlier,4 we obtained systems simultaꢀ
neously containing pyrrole, thiophene, and pyridine rings.
The present work was devoted to the directed synthesis,
properties, and transformations of 3(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridine derivatives.
Alkylation of 3ꢀcyanopyridineꢀ2(1H )ꢀthiones 1a—c
with halides 2a—l in the presence of KOH followed by
the Thorpe—Ziegler cyclization of alkyl derivatives gave
a number of 3ꢀaminothieno[2,3ꢀb]pyridines 3a—p
(Scheme 1). Compounds 3a—c,f—k,n were reported earꢀ
lier,3,5—8 while products 3d,e,l,m,o,p were obtained for
the first time.
Pyrrolylthienopyridines were synthesized by reactions
of 3ꢀaminothieno[2,3ꢀb]pyridines 3 with 2,5ꢀdimethoxyꢀ
tetrahydrofuran in boiling conc. AcOH; the molar ratio of
the reagents was 1 : 1.2 (see Scheme 1). When their
equimolar ratio is used, the reaction time extends apꢀ
proximately two times, while the yield of the product
decreases by 5 to 7%. The starting reagents are well soluble
in acetic acid, which ensures the necessary reaction temꢀ
perature as well. As the result, 3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridines containing aryl (compounds 5a,b),
hetaryl (5ꢀnitroꢀ2ꢀfuryl, 6), ester (7a—k), and tertiary
amide fragments (8a) in position 2 of the thiophene ring
were obtained in good yields (Table 1).
R1 = CH2OMe, R2 = H (1a, 3a—k, 5a, 6, 7b,e,k, 8a);
R
1 = Me, R2 = H (1c, 3n, 7c), Cl (1b, 3l,m,o,p, 5b, 7a,d,f);
R3 = pꢀNO2C6H4 (2a, 3a,l, 5a,b);
(2b, 3b, 6);
COOMe (2c, 3m, 7a); COOEt (2d, 3c,n,о, 7b,c,d);
COOPh (2e, 3d,p, 7e,f); COOC6H4Clꢀp (2f, 3e, 7k);
CONPh2 (2g, 3f, 8a); CONHPh (2h, 3g); CONH2 (2i, 3h);
COOH (2j, 3i); CN (2k, 3j); COPh (2l, 3k);
X = Br (2a—d,l), Cl (2e—h,k), (2i,j)
A substituent in position 2 of thieno[2,3ꢀb]pyridine
was found to significantly affect the possibility of its reacꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 817—823, April, 2004.
1066ꢀ5285/04/5304ꢀ0853 © 2004 Plenum Publishing Corporation

854
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Kaigorodova et al.
Table 1. Physicochemical characteristics and yields of compounds 3d,e,l—p and 5—8
Comꢀ
pound
Yield
(%)
M.p.
/°C
Found
Calculated
Molecular
formula
(%)
С
Н
N
3d
3e
3l
85
87
92
80
75
83
84
86
84
86
86
93
90
92
94
93
91
88
84
88
84
123—124
121—122
>300
62.16
62.18
56.26
56.28
53.95
53.98
48.78
48.80
57.56
57.58
50.60
50.62
57.72
57.74
63.29
63.31
59.44
59.45
58.51
58.53
56.16
56.16
61.78
61.80
63.96
63.98
57.38
57.40
66.63
66.65
62.73
62.74
61.07
61.09
71.48
71.50
63.82
63.84
65.75
65.77
67.48
67.50
4.90
4.91
4.17
4.17
3.61
3.62
4.10
4.10
5.65
5.54
4.59
4.60
3.93
3.94
4.51
4.52
3.68
3.68
4.07
4.09
4.06
4.08
5.48
5.49
5.36
5.37
4.50
4.52
4.78
4.79
3.95
3.95
4.14
4.15
5.10
5.11
6.48
6.48
6.56
6.57
5.40
5.41
8.51
8.53
7.70
C17H16N2O3S
C17H15ClN2O3S
C15H12ClN3O2S
C11H11ClN2O2S
C12H14N2O2S
C12H13ClN2O2S
C16H13ClN2O2S
С20Н17N3O3S
С19Н14СIN3O2S
C18H15N3O4S
C15H13ClN2O2S
C17H18N2O3S
C16H16N2O2S
C16H15ClN2O2S
C21H18N2O3S
C20H15ClN2O2S
C21H17ClN2O3S
C27H23N3O2S
C19H23N3O2S
C21H25N3O2S
C22H21N3O2S
7.72
12.57
12.59
10.33
10.35
11.16
11.19
9.81
9.84
8.40
8.42
11.05
11.07
10.93
10.95
11.36
11.38
8.71
8.73
8.45
8.48
9.32
9.33
8.36
8.37
7.38
7.40
7.30
7.32
6.76
6.78
9.24
9.26
11.73
11.75
10.94
10.96
10.71
10.73
3m
3n
3o
3p
5а
5b
6
205—206
159—160
194—195
238—239
203—204
239—240
200—201
202—203
111—112
148—149
140—141
124—125
148—149
162—163
149—150
168—169
145—146
150—151
7а
7b
7c
7d
7e
7f
7k
8a
8b
8c
8d
tion with dimethoxytetrahydrofuran and the yield of the
product. On attempted involvement of thieno[2,3ꢀb]pyriꢀ
dines containing carboxy, cyano, and phenacyl groups in
position 2 (compounds 3i—k) in this reaction, the starting
reagents were recovered. Primary and secondary amides
(in contrast to tertiary ones, which smoothly react with
dimethoxytetrahydrofuran) give complex mixtures of
products difficult to separate.
of ester 7b with butylꢀ, benzylꢀ, and cyclohexylamines
10a—c easily gives secondary 3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridineꢀ2ꢀcarboxamides 8b—d (see Scheme 2).
The reactions of esters 7b,c with hydrazine hydrate in
ethanol afforded the corresponding hydrazides 11a,b (see
Table 2).
Unlike the corresponding starting thieno[2,3ꢀb]pyriꢀ
dines 3a,c—p, which are colored substances, 3ꢀ(1Hꢀpyrꢀ
rolꢀ1ꢀyl)thieno[2,3ꢀb]pyridines 5, 7—9, and 11 form colꢀ
orless crystals. The exception is 2ꢀ(5ꢀnitroꢀ2ꢀfuryl) deꢀ
By alkaline hydrolysis of esters 7b,d (Scheme 2,
Table 2), carboxylic acids 9a,b were obtained. Amination

3ꢀ(1HꢀPyrrolꢀ1ꢀyl)thieno[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
855
Table 2. Physicochemical characteristics and yields of compounds 9, 11, and 12
Comꢀ Yield M.p. Found
Molecular
formula
(%)
pound
(%)
/°C
Calculated
С
Н
N
9a
96
96
85
81
68
72
233—234
256—257
174—175
219—220
59.56
59.59
54.80
54.82
56.93
56.95
58.74
58.72
60.17
60.19
62.43
62.44
4.66
4.67
3.60
3.61
5.09
5.10
4.91
4.93
4.38
4.38
4.11
4.12
9.24
9.27
9.11
C15H14N2O3S
C14H11ClN2O2S
C15H16N4O2S
C14H14N4OS
C15H13N3O2S
C14H11N3OS
9b
9.13
11a
11b
12a
12b
17.69
17.71
19.55
19.57
14.02
14.04
15.58
15.60
280—281
(decomp.)
>300
Scheme 2
within the "shielding cone" of the perpendicular pyrꢀ
role ring.
To verify the assumption that the pyrrole and the
thienopyridine fragments are mutually perpendicular in
compounds 5—9 and 11, Xꢀray diffraction analysis of
ethyl 4ꢀmethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thiꢀ
eno[2,3ꢀb]pyridineꢀ2ꢀcarboxylate (7b) was carried out.
The projection of the 3D model of compound 7b is shown
in Fig. 1. Interatomic distances and bond and torsion
angles are given in Tables 4—6.
As can be seen from the presented data, the interꢀ
atomic distances and bond angles in structure 7b have
standard values. The thienopyridine fragment is planar
with an average deviation of 0.0117 Å (plane 1). The
pyrrole ring is also planar to within 0.0017 Å (plane 2).
The angle between planes 1 and 2 is 85.1°; i.e., there is no
efficient conjugation between the aromatic thienopyridine
and pyrrole fragments (which is confirmed by the elecꢀ
C(13)
C(10)
C(12)
C(11)
R1 = CH2OMe, R2 = H (9a), R1 = Me, R2 = Cl (9b);
C(14)
R
R
R
1 = CH2OMe (11a), Me (11b)
4 = CONHBu (8b), CONHBn (8c), CONHC6H11 (8d);
4 = Bu (10a), Bn (10b), C6H11 (10c)
O(1)
C(9)
N(2)
C(1)
C(6)
O(2)
C(15)
rivative 6. Apparently, the decolorization is due to steric
hindrances arising when the pyrrole ring is formed. The
pyrrole ring cannot be coplanar with the thieno[2,3ꢀb]pyriꢀ
dine system already bearing bulky substituents in posiꢀ
tions 2 and 4 and thus is approximately perpendicular to
it, which breaks the conjugation between the pyrrole and
thiophene rings. This is indicated by the anomalous upfield
shift (δ 5.47) of the signal for the H(3)Fur proton in the
1H NMR spectrum of nitrofuryl derivative 6 (Table 3),
which can be associated with the position of this proton
C(7)
C(5)
C(4)
C(2)
C(16)
O(3)
C(17)
C(3)
S(1)
N(1)
C(8)
Fig. 1. Projection of the molecular model of compound 7a.

856
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Kaigorodova et al.
1
Table 3. UV, IR, and H NMR spectra of compounds 5—9, 11, and 12
Comꢀ
pound λmax/nm (logε)
UV,
IR,
ν/cm–1
1H NMR,
δ (J/Hz)
5а
5b
6
217 (3.69),
241 (3.63),
343 (3.65)
208 (3.82),
244 (3.77),
340 (3.72)
312 (4.14),
389 (3.72)
1560 (C=C);
1315 (N—O);
2.67 (s, 3 H, 6ꢀMe); 3.23 (s, 3 H, OMe); 4.02 (s, 2 H, CH2O); 6.35 (m, 2 H,
Hβ pyrrole); 6.73 (m, 2 H, Hα pyrrole); 7.27 (d, 2 H, H(2) and H(6) arom.,
1150 (C—O—C) J = 8.5 ); 7.37 (s, 1 H, HPy); 8.13 (d, 2 H, H(3) and H(5) arom., J = 8.5)
1580 (C=C);
1310 (N—O)
1.97, 2.73 (both s, 3 H each, 4ꢀMe, 6ꢀMe); 6.34 (m, 2 H, Hβ pyrrole);
6.78 (m, 2 H, Hα pyrrole); 7.33 (d, 2 H, H(2) and H(6) arom., J = 8.6);
8.13 (d, 2 H, H(3) and H(5) arom., J = 8.6)
2.67 (s, 3 H, 6ꢀMe); 3.22 (s, 3 H, OMe); 4.02 (s, 2 H, CH2O);
5.47 (d, 1 H, H(3)Fur, J = 5.2 ); 6.47 (m, 2 H, Hβ pyrrole);
6.83 (m, 2 H, Hα pyrrole); 7.37 (s, 1 H, HPy);
3100 (C—H);
1580 (C=C);
1360 (N—O);
1150 (C—O—C) 7.47 (d, 1 H, H(4)Fur, J = 5.2)
7а
7b
212 (3.93),
246 (3.84),
298 (3.62)
222 (3.77),
238 (3.71),
298 (3.69)
1710 (C=O);
1530 (C=C);
1230 (C—O—C) 6.73 (m, 2 H, Hα pyrrole)
1700 (C=O);
1530 (C=C);
1.87, 2.73 (both s, 3 H each, 4ꢀMe, 6ꢀMe); 3.75 (s, 3 H, СOOMe);
6.27 (m, 2 H, Hβ pyrrole);
1.16 (t, 3 H, COOCH2Me); 2.63 (s, 3 H, 6ꢀMe); 3.23 (s, 3 H, OMe);
3.93 (s, 2 H, CH2O); 4.17 (q, 2 H, COOCH2Me);
1230 (C—O—C); 6.27 (m, 2 H, Hβ pyrrole); 6.73 (m, 2 H, Hα pyrrole);
1100 (C—O—C) 7.32 (s, 1 H, HPy
)
7c
7d
7e
228(3.76),
241(3.72),
298 (3.65)
212 (3.95),
246 (3.85),
298 (3.64)
208 (3.94),
227(3.78),
305 (3.78)
1690 (C=O);
1570 (C=C);
1.17 (t, 3 H, COOCH2Me); 1.91, 2.59 (both s, 3 H each, 4ꢀMe, 6ꢀMe);
4.17 (q, 2 H, OCH2Me, J = 7.2); 6.23 (m, 2 H, Hβ pyrrole);
1250 (C—O—C) 6.72 (m, 2 H, Hα pyrrole); 7.03 (s, 1 H, HPy
1705 (C=O);
1530 (C=C);
1245 (C—O—C) 6.73 (m, 2 H, Hα pyrrole)
1690 (C=O);
1525 (C=C);
)
1.17 (t, 3 H, OCH2Me, J = 7.2); 1.87, 2.73 (both s, 3 H each, 4ꢀMe, 6ꢀMe);
4.17 (q, 2 H, OCH2Me J = 7.2); 6.27 (m, 2 H, Hβ pyrrole);
2.67 (s, 3 H, 6ꢀMe); 3.23 (s, 3 H, OMe); 3.97 (s, 2 H, CH2O);
6.31 (m, 2 H, Hβ pyrrole); 6.85 (m, 2 H, Hα pyrrole);
1245 (C—O—C); 7.05—7.50 (m, 5 H, Ph);
1105 (C—O—C) 7.43 (s, 1 H, HPy
)
7f
211 (3.75),
248 (3.58),
302 (3.45)
211 (3.79),
245 (3.64),
299 (3.55)
1690 (C=O);
1530 (C=C);
1245 (C—O—C) 7.01—7.21 (m, 5 H, Ph)
1700 (C=O);
1545 (C=C);
1.93, 2.78 (both s, 3 H each, 4ꢀMe, 6ꢀMe); 6.28 (m, 2 H, Hβ pyrrole);
6.71 (m, 2 H, Hα pyrrole);
7k
2.67 (s, 3 H, 6ꢀMe); 3.24 (s, 3 H, OMe); 3.97 (s, 2 H, CH2O);
6.32 (m, 2 H, Hβ pyrrole); 6.84 (m, 2 H, Hα pyrrole);
1260 (C—O—C); 7.07 (d, 2 H, H(2) and H(6) arom., J = 8.7);
1100 (C—O—C) 7.33 (d, 2 H, H(3) and H(5) arom., J = 8.7); 7.43 (s, 1 H, HPy
)
8а
8b
207 (4.12),
233 (3.97),
308 (3.62)
208 (3.79),
303 (3.69),
1640 (C=O);
1580 (C=C)
2.57 (s, 3 H, 6ꢀMe); 3.15 (s, 3 H, OMe); 3.83 (s, 2 H, CH2O);
6.27 (m, 2 H, Hβ pyrrole); 6.53 (s, 2 H, Hα pyrrole);
7.05—7.28 (m, 10 H, 2 Ph); 7.06 (s, 1 H, HPy
0.86 (t, 3 H, Ме, J = 6.9); 1.23 (m, 4 H, CH2CH2); 3.11 (t, 2 H, NCH2, J = 6.9);
2.63 (s, 3 H, 6ꢀMe); 3.23 (s, 3 H, OMe); 3.93 (s, 2 H, CH2O);
)
3410 (N—H);
3100 (C—H);
1640 (C=O);
1580 (C=C)
3395 (N—H);
1620 (C=O);
1580 (C=C)
3410 (N—H);
1610 (C=O);
1550 (C=C);
5.67 (br.s, 1 H, NH); 6.42 (m, 2 H, Hβ pyrrole); 6.93 (m, 2 H, Hα pyrrole);
7.01 (s, 1 H, HPy
)
8c
8d
208 (3.81),
237 (3.71),
300 (3.59)
227 (3.63),
300 (3.58)
2.64 (s, 3 H, 6ꢀMe); 3.19 (s, 3 H, OMe); 3.91 (s, 2 H, CH2O);
4.32 (d, 2 H, NCH2, J = 7.2); 6.33 (m, 2 H, Hβ pyrrole); 6.43 (s, 1 H, NH);
6.93 (m, 2 H, Hα pyrrole); 7.03—7.27 (m, 5 H, Ph); 7.33 (s, 1 H, HPy
0.93 (m, 2 H, Hax(3) and Hax(5)); 1.15 (m, 1 H, Hax(4)); 1.31 (m, 2 H, Hax(2) and
Hax(6)); 1.56 (m, 3 H, Heq(3), Heq(4), Heq(5)); 1.70 (m, 2 H, Heq(2), Heq(6));
2.65 (s, 3 H, 6ꢀMe); 3.23 (s, 3 H, OMe); 3.63 (m, 1 H, CHN); 3.93 (s, 2 H,
)
1100 (C—O—C) CH2O); 5.46 (d, 1 H, NH); 6.43 (m, 2 H, Hβ pyrrole);
6.93 (m, 2 H, Hα pyrrole); 7.33 (s, 1 H, HPy
)
9a
212 (3.89),
239 (3.89),
298 (3.57)
1670 (C=O);
1570 (C=C);
2.63 (s, 3 H, 6ꢀMe); 3.20 (s, 3 H, OMe); 3.87 (s, 2 H, CH2O);
6.26 (m, 2 H, Hβ pyrrole); 6.73 (m, 2 H, Hα pyrrole);
1220 (C—O—C) 7.33 (s, 1 H, HPy); 12.97 (br.s, 1 H, OH)
(to be continued)

3ꢀ(1HꢀPyrrolꢀ1ꢀyl)thieno[2,3ꢀb]pyridines
Table 3 (continued)
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
857
Comꢀ
pound λmax/nm (logε)
UV,
IR,
ν/cm–1
1H NMR,
δ (J/Hz)
9b
211 (3.86),
248 (3.83),
298 (3.28)
208(3.44),
233 (3.49),
307 (3.47)
1695 (C=O);
1560 (C=C)
1.85, 2.71 (both s, 3 H each, C(4)Me, C(6)Me);
6.23 (m, 2 H, Hβ pyrrole); 6.73 (m, 2 H, Hα pyrrole);
12.97 (br.s, 1 H, OH)
2.63 (s, 3 H, 6ꢀMe); 3.20 (s, 3 H, OMe); 3.87 (s, 2 H, CH2O);
4.23 (br.s, 2 H, NH2); 6.37 (m, 2 H, Hβ pyrrole);
6.90 (m, 2 H, Hα pyrrole);
11a
3399, 3315
(N—H);
1615 (C=O);
1585 (C=C);
7.33 (s, 1 H, HPy);
1090 (C—O—C) 7.47 (br.s, 1 H, NH)
11b
301(3.38),
3390, 3310
(N—H);
1620 (C=O);
1590 (C=C)
1640 (C=O);
1590 (C=C);
1.87, 2.57 (both s, 3 H each, 4ꢀMe, 6ꢀMe); 4.23 (br.s, 2 H, NH2);
6.37 (m, 2 H, Hβ pyrrole); 6.93 (m, 2 H, Hα pyrrole);
7.03 (s, 1 H, HPy);
7.43 (br.s, 1 H, NH)
2.59 (s, 3 H, 10ꢀMe); 3.48 (s, 3 H, OMe); 4.76 (s, 2 H, CH2O);
6.57 (m, 1 H, H(2) pyrrole); 7.07 (m, 1 H, H(3) pyrrole);
12a
12b
263 (4.00),
337 (3.81)
1090 (C—O—C) 7.29 (s, 1 H, HPy); 8.13 (m, 1 H, H(1) pyrrole); 11.82 (br.s, 1 H, NH)
1620 (C=O);
1580 (C=C)
262 (3.82),
349 (3.87)
2.49, 2.86 (both s, 3 H each, 10ꢀMe, 8ꢀMe); 6.63 (m, 1 H, H(2) pyrrole);
7.11 (m, 1 H, H(3) pyrrole); 7.19 (s, 1 H, HPy); 8.09 (m, 1 H, H(1) pyrrole);
11.92 (br.s, 1 H, NH)
Table 4. Selected bond lengths (d) in ethyl 4ꢀmethoxymethylꢀ6ꢀ
methylꢀ3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieno[2,3ꢀb]pyridineꢀ2ꢀcarboxyꢀ
late 7b
In the IR spectra, the absorption band of CO stretchꢀ
ing vibrations is shifted to the higherꢀfrequency region by
20 to 55 (for esters 7a—k), 70 (for amide 8a), and ~20 cm–1
(for acid 9a) compared to the spectra of the correꢀ
sponding 3ꢀaminothieno[2,3ꢀb]pyridines 3a—e,f,i,n 7 (see
Tables 2, 3 and Experimental).
Diazotization of 3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieno[2,3ꢀb]pyriꢀ
dineꢀ2ꢀcarbohydrazides 11a,b (Scheme 3) gave acyl azides
13a,b, which are colorless crystals growing dark in air.
Bond
d/Å
Bond
d/Å
S(1)—C(3)
S(1)—C(2)
O(1)—C(9)
O(1)—C(10)
O(2)—C(15)
O(3)—C(15)
O(3)—C(16)
N(1)—C(4)
N(1)—C(3)
N(2)—C(11)
N(2)—C(14)
N(2)—C(1)
C(1)—C(2)
1.7270(19)
1.7338(19)
1.383(3)
1.420(3)
1.193(2)
1.330(2)
1.451(3)
1.332(3)
1.342(2)
1.369(2)
1.372(2)
1.416(2)
1.362(3)
C(1)—C(7)
C(2)—C(15)
C(3)—C(7)
C(4)—C(5)
C(4)—C(8)
C(5)—C(6)
C(6)—C(7)
C(6)—C(9)
C(11)—C(12)
C(12)—C(13)
C(13)—C(14)
C(16)—C(17)
1.435(3)
1.476(3)
1.399(2)
1.402(3)
1.494(3)
1.377(3)
1.415(3)
1.502(3)
1.352(3)
1.402(3)
1.347(3)
1.477(4)
Scheme 3
tronic absorption spectra of compounds 5—9 and 11).
The carboxylate fragment is also planar (all the five atoms
of the ethoxycarbonyl group are coplanar); the average
deviation of the atoms from the plane is 0.0084 Å (plane 3).
The planar ethoxycarbonyl group is rotated about plane 1
through an angle of 7° along the C(2)—C(15) bond; i.e.,
there is an efficient conjugation (π,πꢀinteraction) between
the aromatic thienopyridine fragment and the ethoxyꢀ
carbonyl group.
The presence of the pyrrole ring in structures 5—9 and
11 was confirmed by 1H NMR data. Their spectra contain
multiplet signals for the protons at δ 6.23—6.47 (βꢀproꢀ
tons) and δ 6.59—6.93 (αꢀprotons), with spinꢀspin couꢀ
pling constants characteristic of an Nꢀsubstituted pyrrole.
R = CH2OMe (a), Me (b)
Structure 13 was confirmed by IR spectroscopic data.
In the IR spectra of compounds 13, an intense absorption
band for the stretching vibrations of the azido group apꢀ

858
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Kaigorodova et al.
Table 5. Selected bond angles (ω) in ethyl
4ꢀmethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ
1ꢀyl)thieno[2,3ꢀb]pyridineꢀ2ꢀcarboxylate 7b
Thermal decomposition of acyl azides 13a,b affords
tetracyclic products 12a,b containing an amide CO group
(see Table 3, IR spectra). The H NMR spectra of comꢀ
1
pounds 12a,b show three signals of equal intensity for the
protons of the 1,2ꢀdisubstituted pyrrole ring (see Table 3).
The 1H—1H NOESY 2D homonuclear spectrum of comꢀ
pound 12b contains no cross peak corresponding to the
spinꢀspin coupling between the N(5)H and C(3)H proꢀ
tons. This suggests that these protons are very distant
from each other, thus confirming structure 12.
Bond angle
ω/deg
С(3)—S(1)—C(2)
C(9)—O(1)—C(10)
C(15)—O(3)—C(16)
C(4)—N(1)—C(3)
C(11)—N(2)—C(14)
C(11)—N(2)—C(1)
C(14)—N(2)—C(1)
C(2)—C(1)—N(2)
C(2)—C(1)—C(7)
N(2)—C(1)—C(7)
C(1)—C(2)—C(15)
C(1)—C(2)—S(1)
C(15)—C(2)—S(1)
N(1)—C(3)—C(7)
N(1)—C(3)—S(1)
C(7)—C(3)—S(1)
N(1)—C(4)—C(5)
N(1)—C(4)—C(8)
C(5)—C(4)—C(8)
C(6)—C(5)—C(4)
C(5)—C(6)—C(7)
C(5)—C(6)—C(9)
C(7)—C(6)—C(9)
C(3)—C(7)—C(6)
O(3)—C(15)—C(2)
O(3)—C(16)—C(17)
C(3)—C(7)—C(1)
C(6)—C(7)—C(1)
O(1)—C(9)—C(6)
C(12)—C(11)—N(2)
C(11)—C(12)—C(13)
C(14)—C(13)—C(12)
C(13)—C(14)—N(2)
O(2)—C(15)—O(3)
O(2)—C(15)—C(2)
90.70(9)
111.8(2)
117.11(18)
115.46(16)
108.67(17)
126.70(16)
124.42(16)
123.53(17)
113.18(16)
123.28(15)
127.59(17)
112.72(14)
119.69(14)
126.65(17)
120.46(14)
112.88(13)
122.59(18)
116.45(19)
121.0(2)
121.80(19)
116.64(17)
121.66(18)
121.69(17)
116.84(16)
110.02(17)
106.7(2)
Experimental
1
H NMR spectra were recorded on a Bruker WMꢀ250 instruꢀ
ment (250.13 MHz) in DMSOꢀd6—CCl4 (1 : 3). 1H—1H NOESY
2D homonuclear spectra and 13C NMR spectra with complete
proton decoupling were recorded on a DRXꢀ500 spectrometer
in DMSOꢀd6. IR spectra were recorded on a Specord IR75
instrument (NaCl prisms, suspensions of KBr in Vaseline oil).
UV spectra were recorded on a Specord UVꢀVIS instrument
in EtOH.
The physicochemical characteristics of the compounds obꢀ
tained are given in Tables 1—3.
3ꢀAminoꢀ4ꢀmethoxymethylꢀ6ꢀmethylthieno[2,3ꢀb]pyridines
(3d,e,l,m,o,p). Solutions of a corresponding 3ꢀcyanopyridineꢀ
2(1H )ꢀthione (10 mmol) in 20—25 mL of DMF, 10% KOH
(5.6 mL), and alkyl halide (10 mmol) were mixed. The reaction
mixture was kept for 15 min and 10% KOH (5.6 mL) was added.
The mixture was stirred at ~20 °C for 2.5—3 h and then diluted
with water (10 mL). The precipitate was filtered off, washed
with water, and dried. Compounds 3d,e,l,m,p were recrystallized
from DMF, while compound 3o was recrystallized from EtOH.
IR, ν/cm–1: 3d, 3400, 3310, 1660, 1595, 1100; 3e, 3410,
3320, 1680, 1595, 1080; 3l, 3480, 3405, 1580, 1518, 1230;
3m, 3420, 3320, 1660, 1595; 3o, 3480, 3340, 1650, 1590; 3p, 3510,
3370, 1660, 1580.
110.51(15)
132.64(16)
111.51(18)
107.68(19)
107.9(2)
107.69(19)
108.01(19)
124.37(19)
125.60(18)
1H NMR, δ: 3d, 2.63 (s, 3 H, Me), 3.47 (s, 3 H, OMe), 4.83
(s, 2 H, CH2), 7.03 (br.s, 2 H, NH2), 7.17 (s, 1 H, HPy),
7.19—7.45 (m, 5 H, Ph); 3e, 2.61 (s, 3 H, Me), 3.37 (s, 3 H,
OMe), 4.70 (s, 2 H, CH2), 6.85—7.28 (m, 7 H, ΣNH2, HPy
,
H arom.); 3m, 2.60, 2.73 (both s, 3 H each, Me(6), Me(4)), 3.75
(s, 3 H, COOMe), 6.02 (br.s, 2 H, NH2); 3o, 1.32 (t, 3 H, Me,
J = 7.1 Hz), 2.63, 2.85 (both s, 3 H each, Me(6), Me(4)), 4.27
(q, 2 H, CH2, J = 7.1 Hz), 6.77 (br.s, 2 H, NH2); 3p, 2.63, 2.78
(both s, 3 H each, Me(6), Me(4)), 6.17 (br.s, 2 H, NH2),
7.15—7.39 (m, 5 H, Ph).
Table 6. Selected torsion angles (θ) in ethyl
4ꢀmethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ
1ꢀyl)thieno[2,3ꢀb]pyridineꢀ2ꢀcarboxylate 7b
Torsion angle
θ/deg
UV, λmax/nm (logε): 3d, 293 (5.52), 378 (4.78); 3e, 208
(4.01), 219 (3.93), 292 (3.69), 382 (3.39); 3l, 288 (3.65), 379
(3.16); 3m, 289 (4.00), 373 (3.26); 3o, 289 (4.11), 372 (3.29);
3p, 292 (3.99), 427 (3.52).
Ethyl 4ꢀmethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridineꢀ2ꢀcarboxylate (7b). 2,5ꢀDimethoxytetraꢀ
hydrofuran (0.46 mL, 3.5 mmol) was added to a stirred boiling
solution of compound 3c (0.84 g, 3 mmol) in 4 mL of glacial
AcOH. The reaction mixture was refluxed for 3 h, cooled, and
diluted with ice water (15 mL). The precipitate that formed was
filtered off, washed with water to a neutral reaction, dried, and
recrystallized from EtOH—DMF (5 : 1). The yield of comꢀ
pound 7b was 0.92 g (93%). Compounds 5, 6, 7a,c—k, and 8a
С(5)—С(6)—С(9)—O(1)
С(6)—С(9)—O(1)—C(10)
С(2)—С(1)—N(2)—C(11)
S(1)—С(2)—С(15)—O(2)
С(2)—С(15)—O(3)—C(16)
С(15)—O(3)—С(16)—C(17)
–9.6
–174.6
–88.6
175.9
–176.2
178.1
pears at 2150—2130 cm–1 and the bands of C=O stretchꢀ
ing vibrations are shifted to the higherꢀfrequency region
by 50 to 65 cm–1 compared to those for the starting hydrꢀ
azides 11.

3ꢀ(1HꢀPyrrolꢀ1ꢀyl)thieno[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
859
were obtained analogously. The completion of each reaction
was determined by TLC in hexane—acetone (2 : 1). The reacꢀ
tion was prolonged until the spot of the starting 3ꢀaminoꢀ
thieno[2,3ꢀb]pyridine disappeared. Compounds 5, 6, 7a,c—k,
and 8a were recrystallized from aqueous DMF.
Crystals for Xꢀray diffraction analysis were obtained by reꢀ
peated crystallization of compound 7b from acetone. Colorꢀ
less crystals are monoclinic, C17H18N2O3S, a = 8.490(2) Å,
b = 20.497(4) Å, c = 9.975(2) Å; α = 90.0(3)°, β = 103.80(3)°,
γ = 90.00(3)°, V = 1685.7(6) Å3, dcalc = 1.302 g cm–3, space
group P2(1)/c, Z = 4. The Xꢀray diffraction analysis was carried
out at 293(2) K on a CAD4 automatic diffractometer (MoꢀKα raꢀ
diation, graphite monochromator, θ/2θ scan mode from 2.33°
over P2O5. The yield of azide 13a was 0.65 g (65%), m.p.
112—113 °C (decomp.). IR, ν/cm–1: 2130, 1680, 1580, 1095.
4,6ꢀDimethylꢀ3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieno[2,3ꢀb]pyridineꢀ
2ꢀcarbonyl azide (13b) was obtained by analogy with comꢀ
pound 13a. The yield of azide 13b was 63%, m.p. 108—109 °C
(decomp.). IR, ν/cm–1: 2150, 1670, 1580.
1 0 ꢀ M e t h o x y m e t h y l ꢀ 8 ꢀ m e t h y l ꢀ 4 , 5 ꢀ d i h y d r o p y r i ꢀ
do[3´,2´:4,5]thieno[2,3ꢀe]pyrrolo[1,2ꢀa]pyrazinꢀ4ꢀone (12a).
A suspension of compound 13a (1 g, 3.05 mmol) in 20 mL of
anhydrous toluene was refluxed for 40 min. On cooling, crystals
were filtered off, dried, and recrystallized from DMF. The yield
of compound 12a was 0.62 g (68%).
8,10ꢀDimethylꢀ4,5ꢀdihydropyrido[3,´2´:4,5]thieꢀ
no[2,3ꢀe]pyrrolo[1,2ꢀa]pyridinꢀ4ꢀone (12b) was obtained analoꢀ
gously. 13С NMR, δ: 22.98 (С(8)CH3); 24.35 (C(10)CH3);
110.89 (C(2)H); 111.05 (C(3)); 111.45 (C(5a)); 120.75 (C(10b));
122.11 (C(1)); 123.06 (C(9)); 123.88 (C(10a)); 126.79 (C(3a));
138.38 (C(10)); 152.89 (C=O); 152.95 (C(8)) 154.09 (C(6a)).
to 2θ
= 24.98°). The crystal size is 0.48×0.35×0.28 mm. The
max
number of reflections with I > 3σ was 2206. The structure was
solved by the direct method with the SHELXTL program packꢀ
age9 and refined in the anisotropic (isotropic for H atoms) apꢀ
proximation to R1 = 0.0315 and wR2 = 0.0869. Atomic coordiꢀ
nates have been deposited with the Cambridge Crystallographic
Database.
NꢀButylꢀ4ꢀmethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridineꢀ2ꢀcarboxamide (8b). A solution of compound
7b (0.99 g, 3 mmol) in butylamine (4 mL, 41 mmol) was reꢀ
fluxed for 6.5 h. The reaction mixture was diluted with water
(20 mL). The precipitate that formed was filtered off, washed
with water, dried, and recrystallized from aqueous DMF
(DMF—water, 3 : 1). The yield of carboxamide 8b was 0.92 g
(86%). Compounds 8c,d were obtained analogously.
4ꢀMethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridinecarboxylic acid (9a). To a suspension of ester
7b (0.99 g, 3 mmol) in 10 mL of EtOH 30% KOH (4.54 mmol,
0.19 mL) was added. The reaction mixture was heated until it
was completely homogeneous. On cooling, the mixture was acidiꢀ
fied with 10% HCl to pH ≈3. The precipitate that formed was
filtered off, washed with water, dried, and recrystallized from
dioxane. The yield of acid 9a was 0.87 g (96%). Compound 9b
was obtained analogously.
4ꢀMethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridineꢀ2ꢀcarbohydrazide (11a). Aqueous 85% hydrꢀ
azine (0.85 mL, 27 mmol) was added to a suspension of ester 7b
(0.99 g, 3 mmol) in 20 mL of EtOH. The reaction mixture was
refluxed for 5 h, concentrated to 1/3 of the initial volume, and
then diluted with water. Crystals of compound 11a were filtered
off, washed with water, dried, and recrystallized from DMF.
The yield of carbohydrazide 11a was 0.82 g (85%). Compound
11b was obtained analogously.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 03ꢀ03ꢀ
96636).
References
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4ꢀMethoxymethylꢀ6ꢀmethylꢀ3ꢀ(1Hꢀpyrrolꢀ1ꢀyl)thieꢀ
no[2,3ꢀb]pyridineꢀ2ꢀcarbonyl azide (13a). Conc. H2SO4
(0.23 mL) was added to a solution of compound 11a (1 g,
3.02 mmol) in 7 mL of glacial AcOH. The reaction mixture was
cooled to +5 °С and then NaNO2 (0.29 g, 4.23 mmol) in 1 mL
of water was added for 10 min. The reaction mixture was warmed
to ~20 °C, stirred for 1.5 h, and poured into water with finely
crushed ice. The precipitate that formed was filtered off, washed
with cold water to a neutral reaction, and dried in a desiccator
Received June 4, 2003;
in revised form November 28, 2003