Synthesis of ammonium 5-arylcarbamoyl-4-heteryl-6-methyl-3-cyano-1,4- dihydropyridine-2-thiolates and 4-heteryl-5-carbamoyl-6-methyl-3-cyano-1,4- dihydropyridine-2-selenolates

Article abstract of DOI:10.1007/s11176-005-0248-4

The condensation of enamines derived from acetoacetanilides, heterocyclic aldehydes, and cyanothioacetamide yielded ammonium 5-arylcarbamoyl-5-heteryl-6- methyl-3-cyano-1,4-dihydropyridine-2-thiolates, which were subsequently used for the synthesis of substituted 2-alkylthio-1,4-dihydropyridines, 2-alkylthiopyridines, and thieno[2,3-b]pyridines. The reaction of acetoacetamide with heteroaromatic aldehydes and cyanoselenoacetamide in the presence of N-ethylmorpholine yielded N-ethylmorpholinium 4-heteryl-5-carbamoyl-6-methyl-3- cyano-1,4-dihydrolyridine-2-selenolates, from which substituted 2-alkylseleno-1,4-dihydropyridines were prepared. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11176-005-0248-4

Russian Journal of General Chemistry, Vol. 75, No. 3, 2005, pp. 447 456. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005,
pp. 483 492.
Original Russian Text Copyright
2005 by Dyachenko.
Synthesis of Ammonium 5-Arylcarbamoyl-4-heteryl-6-methyl-
3-cyano-1,4-dihydropyridine-2-thiolates
and 4-Heteryl-5-carbamoyl-6-methyl-3-cyano-
1,4-dihydropyridine-2-selenolates
V. D. Dyachenko
Shevchenko National Pedagogical University, Lugansk, Ukraine
Received September 18, 2003
Abstract The condensation of enamines derived from acetoacetanilides, heterocyclic aldehydes, and cyano-
thioacetamide yielded ammonium 5-arylcarbamoyl-5-heteryl-6-methyl-3-cyano-1,4-dihydropyridine-2-thio-
lates, which were subsequently used for the synthesis of substituted 2-alkylthio-1,4-dihydropyridines, 2-alkyl-
thiopyridines, and thieno[2,3-b]pyridines. The reaction of acetoacetamide with heteroaromatic aldehydes and
cyanoselenoacetamide in the presence of N-ethylmorpholine yielded N-ethylmorpholinium 4-heteryl-5-car-
bamoyl-6-methyl-3-cyano-1,4-dihydrolyridine-2-selenolates, from which substituted 2-alkylseleno-1,4-di-
hydropyridines were prepared.
4-Heteryl-substituted pyridine and 1,4-dihydro-
pyridine derivatives exhibit cardiotonic [1], analgetic
[2], herbicidal [3, 4], and other kinds of biological
activity [5, 6]. Particularly active efforts are made to
find among these compounds calcium channel acti-
vators [7 12].
resulted in aromatization of the dihydropyridine ring
and closure of the thiophene ring; the reaction product
was 3-amino-2-carbamoyl-6-methyl-4-(5-methylthien-
2-yl)-5-(2-methoxyphenylcarbamoyl)thieno[2,3-b]py-
ridine IX. Note that the dehydrogenation of 2-alkyl-
thio-1,4-dihydropyridines under the conditions of the
Thorpe Ziegler reaction was found previously in our
studies of the chemical properties of compounds re-
lated to VIII [13].
Proceeding with the development of new synthetic
routes to 4-heteryl-substituted 1,4-dihydropyridine-2-
thiols (-selenols) [13, 14], which are potentially bio-
active compounds, we studied the condensation of
enamines derived from acetoacetanilides (I) with het-
eroaromatic aldehydes II and cyanoacetamide III. We
found that this reaction (ethanol, 20 C) yields ammo-
nium 4-arylcarbamoyl-4-heteryl-6-methyl-3-cyano-
1,4-dihydropyridine-2-thiolates IV. The reaction ap-
parently involves the Knoevenagel condensation [15]
yielding alkenes V, which subsequently alkylate en-
amine I following the Stork reaction pattern [15] to
give products VI. We failed, however, to isolate these
products because of their easy subsequent regioselec-
tive intramolecular cyclization into compounds IV.
Treatment of a suspension of salt IVa in ethanol
with 10% HCl yields substituted pyridine-2(1H)-thi-
one X. Thus, oxidation of intermediate 1,4-dihydropy-
ridines (apparently, with atmospheric oxygen) occurs
under the conditions of both base and acid catalysis.
The subsequent reaction of pyridinethione X with
alkyl halides VIIl and VIIm in DMF in alkaline solu-
tion yields the corresponding 2-alkylthiopyridines XIa
and XIb whose structure was proved by physicochem-
ical and spectral data (Tables 1, 2).
The condensation of enamine Ib and cyanothioacet-
amide III with furfural IIe yields substituted 3,4-di-
hydropyridine-2(1H)-thione XII and not the corre-
sponding ammonium thiolate. Alkylation of XII with
compounds VIIb VIIe and VIIg VIIk in DMF in the
presence of an alkali yields the corresponding organic
sulfides XIIIa XIIIi. No products of oxidation of the
dihydropyridine core were detected in the reaction
mixture. At the same time, in condensation of en-
amine Ic and cyanothioacetamide III with 3-furan-
carbaldehyde IIf, the corresponding salt or dihydro-
The structures of salts IV were proved by physico-
chemical and spectral methods (Tables 1, 2), and also
by alkylation with alkyl halides VII to obtain sulfides
VIII. This transformation indicates that compounds IV
are salts with the negative charge localized on the
sulfur atom [16], in line with the general relationships
of the chemistry of pyridinechalcogenones [17, 18].
Treatment of substituted 2-carbamoylmethyl-1,4-dihy-
dropyridine VIIIg with 10% aqueous KOH in DMF
1070-3632/05/7503-0447 2005 Pleiades Publishing, Inc.

448
DYACHENKO
Table 1. Constants, yields, melting points, and elemental analyses of salts IVa IVd, XXa, and XXb, dihydropyridines
VIIIa VIIIh, XII, XIIIa XIIIi, XIVa XIVe, XXIIIa, and XIIIb, thieno[2,3-b]pyridine IX, and pyridines X, XIa, XIb,
and XV
Found, %
H
Calculated, %
H
mp,
(solvent for
crystallization)
C
Formula
C
N
C
N
IVa
IVb
IVc
IVd
VIIIa
VIIIb
VIIIc
VIIId
VIIIe
VIIIf
VIIIg
VIIIh
IX
77 147 149a
66.92
58.59
59.39
56.28
64.78
65.94
57.27
54.42
55.04
63.20
57.96
64.11
58.21
66.71
65.70
65.41
57.96
61.72
65.11
64.87
53.30
55.87
62.28
59.28
56.70
57.62
64.58
67.58
68.11
56.12
59.30
63.42
50.95
49.03
46.02
46.12
6.40
4.98
5.90
4.98
5.55
4.30
3.88
4.13
3.97
5.11
4.70
5.04
4.19
4.32
4.28
4.07
3.71
4.03
4.25
4.19
3.29
3.92
4.11
5.14
3.85
4.27
4.70
4.70
4.89
3.87
4.69
3.85
5.64
5.74
3.95
3.17
15.54
14.80
11.42
11.37
11.96
11.79
16.03
11.60
9.12
10.44
12.26
10.12
12.25
15.40
11.12
10.78
11.27
10.87
9.87
9.02
9.54
12.94
7.89
8.49
9.31
9.03
11.05
10.04
9.13
C25H29N5OS
67.09
58.78
59.48
56.49
64.91
66.02
57.34
6.53
5.15
5.82
5.15
5.67
4.48
4.12
3.56
4.13
4.94
4.88
5.18
4.45
4.48
4.34
4.13
3.80
4.19
4.18
4.36
3.45
4.00
4.26
4.98
4.09
4.40
4.83
4.76
5.07
4.00
4.75
4.00
5.71
5.51
3.87
3.33
15.65
14.90
11.56
11.46
12.11
11.85
15.92
11.77
9.19
10.56
12.33
10.29
12.38
15.54
10.97
10.92
11.30
11.09
10.09
9.10
72 295 298a
C23H24ClN5O2S
C24H28N4O3S2
C23H25ClN4O2S2
C25H26N4O3S
C26H21ClN4OS
C21H18ClN5O2S
70 178 180a
81 151 153a
62 153 155 (BuOH)
61 188 190 (BuOH)
82 241 243 (BuOH)
70 235 237 (BuOH)
81 203 204 (BuOH)
74 212 214 (AcOH)
63 115 117 (AcOH)
69 173 176 (AcOH)
76 305 308b (DMF)
68 288 290 (AcOH)
C27H21BrClN5O2S 54.51
C28H25BrN4O3S2
C28H26N4O3S2
C22H22N4O3S2
C29H28N4O3S2
C22H20N4O3S2
C20H16N4OS
55.17
63.38
58.13
63.95
58.39
66.65
65.87
65.56
58.14
61.84
64.92
65.00
X
XIa
XIb
XII
94
68 70 (EtOH)
C28H22N4O4S
84 207 209 (AcOH)
77 275 277b (EtOH)
65 278 279 (AcOH)
62 235 238 (AcOH)
72 178 179 (BuOH)
68 274 275 (BuOH)
69 278 280 (AcOH)
91 175 177 (AcOH)
73 159 160 (BuOH)
80 193 194 (AcOH)
69 166 169 (EtOH)
57 220 221 (BuOH)
64 201 203 (BuOH)
65 158 160 (EtOH)
63 233 235 (AcOH)
60 217 219 (BuOH)
72 210 212 (AcOH)
64 261 263a
C28H21ClN4O2S
C18H14ClN3O2S
C26H21ClN4O3S
C30H23ClN4O3S
C25H20ClN3O2S
XIIIa
XIIIb
XIIIc
XIIId
XIIIe
XIIIf
XIIIg
XIIIh
XIIIi
XIVa
XIVb
XIVc
XIVd
XIVe
XV
C26H20BrClN4O3S 53.48
9.60
13.06
8.08
8.65
9.47
C20H17ClN4O3S
C27H22ClN3O4S
C24H24ClN3O4S
C21H18ClN3O4S
C22H20ClN3O4S
C27H24N4O4S
C31H26N4O4S
C26H23N3O3S
C27H23BrN4O4S
C21H20N4O4S
C28H21ClN4O3S
C18H24N4O3Se
C18H24N4O2SSe
C13H13N3OSSe
C14H12N4OSSe
56.01
62.36
59.32
56.82
57.70
64.79
67.61
68.25
55.96
59.42
63.57
51.07
49.20
46.16
46.29
9.18
11.19
10.18
9.18
9.54
9.67
13.37
10.38
13.40
12.80
12.28
15.30
13.20
10.59
13.23
12.75
12.42
15.42
XXa
XXb
XXIIIa
XXIIIb
67 183 185a
80 191 193 (BuOH)
71 188 190 (MeOH)
a
b
c
Was not recrystallized.
Sublimes at 240 C.
Sublimes at 200 C.
pyridinethione were not isolated. Chromatographic
analysis showed a complex composition of the mix-
ture. Addition of alkyl halides resulted in formation of
substituted 2-alkylthio-1,4-dihydropyridines XIVa
XIVe in yields not exceeding 65%.
agent in condensation of enamine Ib and cyanothio-
acetamide III with pyridinecarbaldehyde IIb results in
formation of substituted pyridine XV.
Our results show that multicomponent condensa-
tion involving enamines derived from acetoacetani-
lides (I), heteroaromatic aldehydes II, cyanothioacet-
The use of benzyl chloroacetate VIIj as alkylating
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

SYNTHESIS OF AMMONIUM 5-ARYLCARBAMOYL-4-HETERYL-6-METHYL-3-CYANO-...
449
1
Table 2. IR and H NMR spectra of salts IVa IVd, XXa, and XXb, dihydropyridines VIIIa VIIIh, XII, XIIIa XIIIi,
XIVa XIVe, XXIIIa, and XIIIb, thieno[2,3-b]pyridine IX, and pyridines X, XIa, XIb, and XV
IR spectrum,
1H NMR spectrum, , ppm (J, Hz)
1
, cm
(C N), (CH),
(C=O) (CONH) N1H (s) C6Me (s)
CONH (s), C4H (s),
other signals
IVaa
IVba
2175
2188
3310,
1684
3324,
3667
9.27, 8.65 4.58, 2.12 1.57 m [6H, (CH2)3], 1.80 s (3H, Me), 3.00 t (4H, CH2NCH2, J 4.68),
7.06 7.63 m (5H, H arom.), 7.81 s (1H, C2H), 8.39 m (2H, H arom.)
9.34, 7.94 4.55, 2.08 3.08 t (4H, CH2NCH2, J 4.65), 3.75 t (4H, CH2OCH2, 7.13 d (2H,
C2H and C6H of pyridine, J 9.02), 7.24 d and 7.56 d (2H each, C6H4, J
6.01), 8.41 d (2H, C3H and C5H of pyridine)
8.21, 8.01 4.43, 2.20 2.37 s (3H, Me), 3.03 t (4H, CH2NCH2, J 4.65), 3.70 s (3H, MeO),
3.82 t (4H, CH2OCH2), 6.64 m (3H, H arom.), 6.92 m (2H, H arom.),
8.15 d (1H, C3H of thiophene, J 3.32)
IVca
IVda
2182
2190
3330,
1672
3330,
1664
9.22, 7.91 4.95, 2.19 2.06 s (3H, Me), 3.06 t (4H, CH2NCH2, J 4.66), 3.77 t (4H, CH2OCH2),
6.63 d (1H, C4H of thiophene, J 5.04), 7.00 d (1H, C5H of thiophene),
7.12 d and 7.54 d (2H each, C6H4, J 8.84)
VIIIa 2202, 3295,
9.10, 9.04 4.88, 2.18 0.95 t (3H, CH3CH2CH2, J 7.20), 1.62 m (2H, CH3CH2CH2), 1.89 s
2
1730
1660
(3H, Me), 3.85 d and 3.94 d (1H each, SCH2, J 16.0), 4.05 t (2H,
OCH2, J 7.15), 7.08 m (4H, C6H4), 7.33 d.d (1H, C5H of pyridine, J
2.70), 7.55 d (1H, C4H of pyridine, J 5.18), 8.96 d (2H, C6H of
pyridine)
2
VIIIb 2196
VIIIc 2210
VIIId 2207
VIIIe 2188
3327,
1655
9.60, 9.21 4.75, 2.13 4.23 d and 4.26 d (1H each, SCH2, J 5.72), 6.96 d (2H, C3H and C5H
of pyridine, J 4.64), 7.16 d and 7.55 d (2H each, C6H4, J 8.84),
7.28 br.s (5H, Ph), 8.39 d (2H, C2H and C6H, J 4.30)
3339,
1660
10.35,
9.66
4.80, 2.16 3.16 s (2H, SCH2), 7.17 m (4H, H arom.), 7.56 m (3H, H arom. and
NH2), 7.93 br.s (1H, NH2), 8.45 d (2H, C2H and C6H of pyridine,
J 1.62)
3346,
1677
10.50,
9.68
4.82, 2.17 3.86 s (2H, SCH2), 7.19 m (4H, H arom.), 7.40 d (2H, H arom., J 8.78),
7.56 m (4H, H arom.), 8.43 d (2H, C2H and C6H of pyridine, J 3.82),
9.66 s (1H, NHCO)
3296,
1665
10.49,
8.31
4.71, 2.79 2.43 s (3H, Me), 3.73 s (3H, MeO), 3.84 d and 3.87 d (1H each, SCH2,
2J 12.52), 6.63 d (1H, C3H of thiophene, J 3.50), 6.76 d (1H, H arom.,
J 3.42), 6.87 t (1H, H arom., J 5.14), 6.92 d (1H, H arom., J 5.14),
7.05 t (1H, H arom., J 5.03), 7.48 d and 7.55 d (2H each, 4-BrC6H4, J
8.86), 7.94 d (1H, C4H of thiophene, J 3.50), 9.63 s (1H, NHCO)
4.37, 2.30 2.43 s (3H, Me), 3.73 s (3H, MeO), 3.84 d and 3.87 d (1H each, SCH2,
2J 12.32), 6.62 d (1H, C3H of thiophene, J 3.32), 6.78 6.93 m (4H,
H arom.), 7.06 t (1H, H arom., J 7.60), 7.24 t (2H, H arom., J 7.48),
7.60 d (2H, H arom., J 7.56), 8.13 d (1H, C4H of thiophene, J 3.32)
VIIIf 2195
VIIIg 2200
VIIIh 2204
IX
3308,
1654
10.38,
8.10
2
3345,
1674
10.57,
8.19
4.70, 2.25 2.44 s (3H, Me), 3.55 d and 3.64 d (1H each, SCH2, J 14.94), 3.72 s
(3H, MeO), 6.64 d (1H, C3H of thiophene, J 3.18), 6.77 6.98 m (4H,
C6H4), 7.60 br.s and 7.93 br.s (1H each, NH2), 8.07 d (1H, C4H of
thiophene)
3296,
1666
10.14,
8.05
4.71, 2.27 2.29 s (3H, Me), 2.45 s (3H, Me), 3.73 s (3H, MeO), 3.88 s (2H,
SCH2), 6.23 d (1H, C3H of thiophene, J 3.34), 6.79 7.20 m (H,
H arom.), 7.46 d (1H, H arom., J 7.58), 8.15 d (1H, C4H of thiophene),
9.77 s (1H, CONH)
3204,
3345,
3412,
1676
9.35
2.50
2.64 s (3H, Me), 3.79 (3H, MeO), 5.97 br.s (2H, C3NH2), 6.78 7.02 m
(7H, H arom. and CONH2), 7.66 d (1H, H arom., J 7.02)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

450
DYACHENKO
Table 2. (Contd.)
IR spectrum,
1H NMR spectrum, , ppm (J, Hz)
1
, cm
(C N), (CH),
(C=O) (CONH) N1H (s) C6Me (s)
CONH (s), C4H (s),
other signals
Xb
2224
3397,
1658
9.76
9.20
2.54
2.44
1.87 s (3H, Me), 7.06 m (4H, C6H4), 7.54 d.d (1H, C4H of pyridine, J
4.55), 7.89 t and 7.91 t (1H, C5H of pyridine, J 1.92), 8.68 s (1H, C2H
of pyridine), 8.73 d (1H, C6H of pyridine, J 1.90)
1.85 s (3H, Me), 4.82 s (2H, SCH2), 6.89 d (1H, H arom., J 4.13),
6.98 d (1H, H arom., J 2.43), 7.09 m (3H, H arom.), 7.44 s (1H,
H arom.), 7.52 m (2H, H arom.), 7.90 m (1H, H arom.), 8.68 d (2H,
H arom., J 8.25), 9.76 br.s (2H, 2OH)
XIa
2218, 1675
1703
XIb
XII
2226, 1673
1714
9.75
2.38
4.97
1.89 s (3H, Me), 4.90 s (2H, SCH2), 7.02 m (4H, H arom.), 7.53 m (1H,
H arom.), 7.62 d and 8.14 d (2H each, 4-ClC6H4, J 8.29), 7.90 d (1H,
H arom., J 5.01), 8.69 m (2H, H arom.)
2254
1662
11.98,
9.96
d
4.54 d (1H, C3H of pyridine, J 10.02), 6.33 d (1H, C3H of furan, J
(J 10.02), 1.94), 7.36 7.60 m (6H, H arom.)
2.13
10.35,
9.59
XIIIa 2188
XIIIb 2197
3334,
1675
4.94,
2.16
3.83 s (2H, SCH2), 6.09 d (1H, C3H of furan, J 3.10), 6.23 d.d (1H,
C4H of furan, J 1.84), 7.01 7.37 (7H, H arom.), 7.58 m (3H, H arom.),
9.80 br.s (1H, CONH)
3302,
1677
10.43,
9.64
4.99, 2.16 3.96 d and 4.09 d (1H each, SCH2, 2J 14.66), 6.12 d (1H, C3H of furan,
J 3.12), 6.27 e. d (1H, C4H of furan, J 1.78), 7.19 d and 7.63 d (2H
each, C6H4, J 8.80), 7.53 m (4H, H arom.), 7.75 d (2H, H arom., J
7.22), 7.86 d (1H, C5H of furan, J 2.30), 8.12 d (1H, H arom., J 8.24),
9.82 br.s (1H, CONH)
XIIIc 2202
XIIId 2200
3295,
1590
9.58, 9.19 4.82, 2.11 4.14 d and 4.32 d (1H each, SCH2, 2J 13.08), 5.95 d (1H, C3H of furan,
J 2.82), 6.25 d.d (1H, C4H of furan, J 1.76), 7.18 d and 7.60 d (2H
each, C6H4, J 8.80), 7.28 m (5H, Ph), 7.41 d (1H, C5H of furan, J 1.14)
3334,
1645
10.47,
9.62
4.97, 2.14 3.06 s (2H, SCH2), 6.09 d (1H, C3H of furan, J 3.08), 6.25 d.d (1H,
C4H of furan, J 1.84), 7.19 d and 7.61 d (2H each, 4-ClC6H4, J 8.84),
7.39 d (1H, C5H of furan, J 1.96), 7.42 d and 7.54 d (2H each,
4-BrC6H4, J 9.00), 9.63 s (1H, CONH)
XIIIe 2189
3302,
3415,
1587
10.32,
9.60
4.93, 2.14 3.58 s (2H, SCH2), 6.08 d (1H, C3H of furan, J 2.96), 6.27 d.d (1H,
C4H of furan, J 1.12), 7.18 d and 7.60 d (2H each, C6H4, J 8.80),
7.40 d (1H, C5H of furan, J 1.74), 7.55 br.s and 7.90 br.s (1H each, NH2)
XIIIf 2203, 3332,
1711 1618
9.63, 9.18 4.97, 2.06 3.80 d and 4.04 d (1H each, SCH2, 2J 15.40), 5.13 s (2H, OCH2),
6.08 d (1H, C3H of furan, J 2.70), 6.26 d.d (1H, C4H of furan, J 2.02),
7.20 d and 7.63 d (2H each, C6H4, J 8.78), 7.33 m (5H, Ph), 7.35 d
(1H, C5H of furan, J 1.69)
XIIIg 2208, 3315,
1714 1672
9.61, 9.17 4.98, 2.11 0.93 t (3H, Me, J 6.14), 1.38 m (2H, CH2), 1.60 m (2H, CH2), 3.74 d
2
and 3.95 d (1H each, SCH2, J 15.46), 4.08 t (2H, OCH2, J 6.56),
6.09 d (1H, C3H of furan, J 3.06), 6.27 d.d (1H, C4H of furan, J 1.84),
7.19 d and 7.62 d (2H each, C6H4, J 8.84), 7.42 d (1H, C5H of furan,
J 1.70)
XIIIh 2202, 3307,
1719 1645
9.65, 9.20 4.93, 2.11 3.69 s (3H, MeO), 3.78 d and 3.94 d (1H each, SCH2, 2J 15.46), 6.09 d
(1H, C3H of furan, J 3.04), 6.26 d.d (1H, C4H of furan, J 1.64), 7.19 d
and 7.62 d (2H each, C6H4, J 7.90), 7.42 d (1H, C5H of furan, J 0.80)
2
XIIIi 2198, 3295,
1714 1668
9.59, 9.17 4.92, 2.12 1.27 t (3H, Me, J 6.24), 3.72 d and 3.91 d (1H each, SCH2, J 15.08),
4.14 q (2H, OCH2, J 6.24), 6.09 d (1H, C3H of furan, J 3.34), 6.27 d.d
(1H, C4H of furan, J 2.18), 7.18 d and 7.69 d (2H each, C6H4, J 8.58),
7.40 d (1H, C5H of furan, J 1.90)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

SYNTHESIS OF AMMONIUM 5-ARYLCARBAMOYL-4-HETERYL-6-METHYL-3-CYANO-...
Table 2. (Contd.)
451
IR spectrum,
1H NMR spectrum, , ppm (J, Hz)
1
, cm
(C N), (CH),
CONH (s), C4H (s),
other signals
(C=O) (CONH) N1H (s) C6Me (s)
XIVa 2196
XIVb 2190
3300,
1663
10.40,
8.16
4.41, 2.28 3.78 s (3H, MeO), 6.43 s (1H, C2H of furan), 6.87 m (3H, H arom.),
7.03 t (1H, H arom., J 7.52), 7.29 t (2H, H arom.), 7.50 d (2H, H arom.,
J 9.04), 7.60 d (2H, H arom., J 7.90), 8.09 d (1H, H arom., J 7.72),
9.91 br.s (1H, CONH)
3341,
1672
10.41,
8.16
4.51, 2.24 3.75 s (3H, MeO), 4.97 d and 5.06 d (1H each, SCH2, 2J 16.15), 6.42 s
(1H, C2H of furan), 6.86 m (3H, H arom.), 7.57 m (5H, H arom.),
7.75 d.d (2H, H arom., J 4.38), 7.86 d (1H, H arom., J 6.44), 8.07 d.d
(2H, H arom., J 4.66), 9.90 br.s (1H, CONH)
XIVc 2205
XIVd 2198
XIVe 2191
3294,
1666
9.21, 8.16 4.39, 2.21 3.76 s (3H, MeO), 4.14 d and 4.27 d (1H each, SCH2, 2J 12.38), 6.28 s
(1H, C2H of furan), 6.87 m (3H, H arom.), 7.28 m (5H, Ph), 7.39 m
(1H, H arom.), 7.48 m (1H, H arom.), 8.04 m (1H, H arom.)
10.43,
8.15
3337,
1670
4.49, 2.25 3.78 s (3H, MeO), 3.70 d and 3.96 d (1H each, SCH2, 2J 14.19), 6.41 s
(1H, C5H of furan), 6.90 m (4H, H arom.), 7.38 7.58 m (5H, H arom.),
8.05 d (1H, H arom., J 7.66), 9.77 br.s (1H, CONH)
2
3345,
1662
10.34,
8.23
4.49, 2.23 3.50 d and 3.71 d (1H each, SCH2, J 17.11), 3.77 s (3H, MeO), 6.41 s
(1H, C2H of furan), 6.91 m (4H, H arom.), 7.49 m (1H, H arom.),
7.58 br.s and 7.92 br.s (1H each, NH2), 8.02 d (1H, H arom., J 7.78)
XV
2222, 1668
1718
10.44
7.95
2.47
4.20 s (2H, SCH2), 5.19 s (2H, OCH2), 7.20 d (2H, C6H4, J 8.82),
7.36 m (9H, H arom.), 8.64 d (2H, C2H and C6H of pyridine, J 4.66)
XXaa 2180
3330,
3456,
1674
4.48, 2.08 1.15 t (3H, Me, J 6.25), 2.96 m (6H, CH2NCH2 and CH3CH2), 3.74 t
(4H, CH2OCH2, J 4.38), 5.93 d (1H, C3H of furan, J 2.96), 6.28 d.d
(1H, C4H of furan, J 2.40), 6.65 br.s (2H, NH2), 7.45 d (1H, C5H of
furan, J 1.20)
XXba 2175
XXIIIa 2188
3300,
3474,
1682
3420,
1684
8.03
4.67, 2.09 1.17 t (3H, Me, J 6.25), 3.05 m (6H, CH2NCH2 and CH3CH2 ),
6.65 br.s (2H, NH2), 6.88 m (2H, C3H and C4H of thiophene), 7.24 d
(1H, C5H of thiophene, J 4.6)
9.09
9.30
4.88, 2.10 2.39 s (3H, Me), 6.90 m (2H, C3H and C4H of thiophene), 8.11 br.s
(2H, NH2), 7.36 d (1H, C5H of thiophene, J 4.01)
XXIIIb 2200, 3338,
2252 1660
4.99, 2.12 3.98 s (2H, CH2), 6.84 m (4H, C3H and C4H of thiophene and NH2),
3.42 d (1H, C5H of thiophene, J 3.98)
a
+
b
1
The N H proton signal is not observed, probably besause of deuterium exshange. The N H proton signal is not observed, probably
besause of deuterium exchange.
amide III, and alkyl halides VII is a convenient route
to ammonium 5-arylcarbamoyl-4-heteryl-6-methyl-3-
cyano-1,4-dihydropyridine-2-thiolates IV, 2-alkylthio-
1,4-dihydropyridines VIII, XIII, and XIV, and the
corresponding dehydrogenated analogs XI and XIV
(Scheme 1).
ano-1,6-dihydropyridine-2-selenolate XVII, which
was prepared previously by the reaction of the aceto-
acetanilide enamine with cyano selenoacetamide [19]
(Scheme 2).
The replacement of enamine I by acetoacetamide
XVIII and the use of morpholine as catalyst result in
cyclodimerization of cyano selenoamide XVI to 4,6-di-
amino-3-cyanopyridine-2(1H)-selenone XIX, which
was prepared previously by treatment of XVI with
bases [20] (Scheme 3).
It appeared impossible to prepare by Scheme 1
selenium analogs of compounds IV by using cyano-
selenoacetamide XVI instead of cyanothioacetamide
III because of the predominance of the competing
condensation of enamine I with CH acid XVI. The
reaction yielded morpholinium 4-methyl-6-oxo-3-cy-
With N-ethylmorpholine used as catalyst in the
reaction of acetoacetamide XVIII with cyanoseleno-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

452
DYACHENKO
Scheme 1.
O
O
Ht
O
HtCHO (IIa IIf),
ArHN
Me
NCCH2C(S)NH2 (III)
CN
CN
S
HN
N
Me
Z
H2N
S
N
X
H
Cl
Ia Id
V
XIIIa XIIIi
VIIb VIIe, VIIg VIIk/KOH
I
N
O
Ht
O
VIIj
O
O
CN
ArHN
Me
CN
S
CN
S
HN
HN
H2N
S
O
N
Me
Me
N
N
H
Cl
Cl
O
Z
P
h
X
XV
VI
XII
O
VIIb VIIe, VIIg
Ht
O
Ht
O
Hlg
Z
VIIa VIIf
CN
CN
ArHN
O
ArHN
OMe
CN
S
Me
+
S
Me
N
H
HN
S
N
H
H2N
X
Me
Z
N
H
VIIIa VIIIh
IVa IVh
XIVa XIVe
H+
KOH DMF
Me
N
N
VIIl, VIIm,
S
KOH
O
O
O
NH2
Me
OMe
HN
Me
CN
CN
NH2
O
HN
HN
Me
Me
Me
S
N
S
Z
N
N
S
H
IX
X
XIa, XIb
I, Ar = 2-MeC6H4, X = CH2 (a); Ar = 4-ClC6H4, X = O (b); Ar = 2-MeC6H4, X = O (c); Ar = 4-ClC6H4, X = CH2 (d);
II, Ht = 3-pyridyl (a), 4-pyridyl (b), 5-methylthien-2-yl (c), 3-methylthien-2-yl (d), 2-furyl (e), 3-furyl (f); IV, Ar =
2-MeC6H4, Ht = 3-pyridyl, X = CH2 (a); Ar = 4-ClC6H4, Ht = 3-pyridyl, X = O (b); Ar = 2-MeOC6H4, Ht = 5-methylthien-
2-yl, X = O (c); Ar = 4-ClC6H4, Ht = 3-methylthien-2-yl, X = O (d); VII, Hlg = Cl (a k), Br (l, m); VII, Z = CO2Pr (a),
Ph (b), CONH2 (c), 4-BrC6H4NHCO (d), PhNHCO (e), 2-MeC6H4NHCO (f), 1-naphthylcarbamoyl (g), CO2Et (h),
CO2Me (i), CO2CH2Ph (j), CO2Bu (k), 3,4-(HO)2C6H3CO (l), 4-ClC6H4 (m); VIII, Ar = 2-MeC6H4, Ht = 3-pyridyl (a);
Ar = 4-ClC6H4, Ht = 4-pyridyl (b d); Ar = 2-MeOC6H4, Ht = 5-methylthien-2-yl (e h); VIII, Z = CO2Pr (a), Ph (b),
CONH2 (c, g), 4-BrC6H4NHCO (d, e), PhNHCO (f), 2-MeC6H4NHCO (h); XI, Z = 3,4-(HO)2C6H3CO (a), 4-ClC6H4CO
(b); XIII, XIV, Z = PhNHCO (a), 1-naphthylcarbamoyl (b), Ph (c), 4-BrC6H4NHCO (d), CONH2 (e), CO2CH2Ph (f),
CO2Bu (g), CO2Me (h), CO2Et (i).
acetamide XVI and heteroaromatic aldehydes IIf and
IIg, the reaction changes pathway toward formation of
N-ethylmorpholinium 4-heteryl-5-carbamoyl-6-meth-
yl-3-cyano-1,4-dihydropyridine-2-selenolates XX. The
reaction involves the Knoevenagel condensation re-
sulting in formation of hetarylmethylenecyanoseleno-
acetamides XXI in situ. They can be obtained and
isolated by two-component condensation of aldehydes
IIf and IIg with cyanoselenoacetamide XVI [21]. The
subsequent reaction involves formation of the corre-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

SYNTHESIS OF AMMONIUM 5-ARYLCARBAMOYL-4-HETERYL-6-METHYL-3-CYANO-...
453
Scheme 2.
O
N
Me
Me
CN
CN
Ic, IIe
CN
Se
NHH2N
S
e
H2N
O
MeO
S
e
NH2
O
N
H
+
XVI
H2N
O
OMe
XVII
Scheme 3.
CN
(XVIe),
H2N
Se
NH
NH2
O
CN
Se
O
NH
CN
Se
H2N
Me
XVIII
H2Se
H2N
H N
2
Se
H2N
O
N
H
XIX
II, Ht = 2-thienyl (g); VII, Hlg = I, Z = H (n), Hlg = Cl, Z = CN (o); XX, Ht = 2-furyl (a), 2-thienyl (b); XXIII, Z = H
(a), CN (b).
Scheme 4.
Ht
O
O
NEt
H2O
CN
Se
CN
Se
H2N
+
HtCHO +
H2N
O
H2N
XVI
Me
IIf, IIg
XVIII
XXI
XVIII
S
Hlg
VIIn, VIIo
Z
Ht
Ht
O
O
O
H2O
CN
Se
CN
Se
H2N
Me
CN
H2N
Me
H2N
+
N
H
S
Z
Me
H2N
O
N
O
NHEt
H
XXIIIa, XXIIIb
XXa, XXb
XXII
1
1
sponding Michael adducts XXII whose regioselective
cyclization yields substituted ammonium 1,4-dihydro-
pyridine-2-selenolates XX (Scheme 4).
at 2175 2200 cm . The H NMR spectra of XX and
XXIII contain, along with the signals of protons in
substituents (Tables 1, 2), also characteristic signals of
the N1H and C4H protons of the 1,4-dihydropyridine
ring at 7.95 9.30 and 4.48 4.99 ppm, respectively,
which is consistent with published data [22 25].
The structures of salts XX were confirmed by their
transformation into the corresponding organic sele-
nides XXIII by alkylation with VIIn and VIIo. The IR
spectra of substituted 1,4-dihydropyridines XX and
XXIII contain characteristic absorption bands of the
stretching vibrations of the conjugated cyano group
EXPERIMENTAL
The IR spectra were taken on an IKS-29 spectrom-
eter (mulls in mineral oil). The H NMR spectra were
1
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

454
DYACHENKO
taken on Bruker WP-100SY (100 MHz, compounds
IVa, IVb, X, XII, XVII, XIX, XXa, XXb, XXIIIa,
XXIIIb), Gemini-200 (199.975 MHz, compounds
IVd, VIIIb VIIId, VIIIg, VIIIh, XIIIa XIIIi, XIVa,
XIVc XIVe, XV), Bruker AC-200 (200.13 MHz,
compound VIIIa), Bruker WM-250 (250.13 MHz,
compound XIb), Bruker AM-300 (300.13 MHz, com-
pound IVc), and Bruker DR-500 (500.13 MHz, com-
pounds VIIIe, VIIIf, IX, XIa, XIVb) spectrometers
in DMSO-d6, internal reference Me4Si. The mass
spectra were recorded on a Kratos MS-890 spectrom-
eter (70 eV) (Table 3). The melting points were
determined with a Koefler unit. The reaction progress
was monitored by TLC (Silufol UV-254, acetone
hexane, 3 : 5, development with iodine vapor).
alkyl halide VII. The resulting mixture was stirred
for 2 h and allowed to stand for a day at room tempera-
ture. Then the mixture was diluted with an equal
volume of water, and the precipitate was separated
and washed with water, ethanol, and hexane.
6-Methyl-4-(2-furyl)-5-(4-chlorophenylcarba-
moyl)-3-cyano-3,4-dihydropyridine-2(1H)-thione
XII was prepared similarly to IV starting from ena-
mine Ib, furfural IIe, and cyanothioacetamide III.
6-Methyl-4-(2-furyl)-5-(4-chlorophenylcarba-
moyl)-3-cyano-2-Z-methylthio-1,4-dihydropyridi-
nes XIIIa XIIIi were prepared similarly to XI starting
from 3,4-dihydropyridinethione XII and appropriate
alkyl halides VII.
Ammonium 5-arylcarbamoyl-4-hetaryl-6-me-
thyl-3-cyano-1,4-dihydropyridine-2-thiolates IVa
IVd. A mixture of appropriate enamine derived from
acetoacetanilide (I), heteroaromatic aldehyde II, and
cyanothioacetamide III (10 mmol each) in 15 ml of
ethanol was stirred for 15 20 min at 20 C to obtain a
homogeneous phase, after which the mixture was al-
lowed to stand at 20 C for a day. The precipitate was
filtered off and washed with ethanol and hexane.
6-Methyl-5-(2-methoxyphenylcarbamoyl)-4-(3-
furyl)-3-cyano-2-Z-methylthio-1,4-dihydropyri-
dines XIVa XIVe. A mixture of 2.6 g of Ic, 0.9 ml
of 3-furancarbaldehyde IIf, and 1.0 g of cyanothioacet-
amide III in 15 ml of ethanol was stirred for 15 min
at 20 C until the starting reactants fully dissolved,
after which it was allowed to stand at 20 C for a day.
Then 10 mmol of appropriate alkyl halide VII was
added, and the mixture was stirred for 2 h and then
allowed to stand for 48 h, after which it was diluted
with an equal volume of water. The precipitate was
filtered off.
5-Arylcarbamoyl-4-hetaryl-2-Z-methylthio-6-
methyl-3-cyano-1,4-dihydropyridines VIIIa VIIIh.
A suspension containing appropriate salt IV and alkyl
halide VIII (10 mmol each) in 12 ml of DMF was
stirred for 5 h at 20 C and then diluted with an equal
volume of water. The precipitate was filtered off and
washed with water, ethanol, and hexane.
5-Benzyloxycarbonylmethylthio-6-methyl-4-(4-
pyridyl)-5-(4-chlorophenylcarbamoyl)-3-cyanopyri-
dine XV was prepared similarly to XIV starting from
enamine Ib, 4-pyridinecarbaldehyde IIb, cyanothio-
acetamide III, and benzyl chloroacetate VIIj.
3-Amino-6-methyl-4-(5-methylthien-2-yl)-5-(2-
methoxyphenylcarbamoyl)-2-carbamoylthieno[2,3-
b]-pyridine IX. A 5.6-ml portion of 10% aqueous
KOH was added with stirring to a solution of 4.5 g of
VIIIg in 15 ml of DMF. The mixture was allowed to
stand at room temperature for 48 h, after which it was
diluted with an equal volume of water. The precipitate
was filtered off and washed with water, ethanol, and
hexane.
Morpholinium 4-methyl-6-oxo-3-cyano-1,6-di-
hydropyridine-2-selenolate XVII. A mixture of
1.5 g of cyanoselenoacetamide XVI, 2.6 g of enamine
Ic, and 0.83 ml of furfural IIe in 15 ml of absolute
ethanol was stirred for 15 min at 20 C under argon
and then allowed to stand at 20 C for a day. The pre-
cipitate was filtered off and washed with absolute
ethanol and hexane; yield 64%. The melting point and
1H NMR spectrum are in agreement with published
data [19].
6-Methyl-5-(2-methylphenylcarbamoyl)-4-(3-py-
ridyl)-3-cyanopyridine-2(1H)-thione X. A stirred
suspension of 4.5 g of IVa in 20 ml of ethanol was
slowly acidified with 10% HCl to pH 6. The resulting
solution was filtered and kept for 48 h at room tem-
perature. The crystalline precipitate of X was filtered
off and washed with water, ethanol, and hexane.
4,6-Diamino-3-cyanopyridine-2(1H)-selenone
XIX. A mixture of 1.5 g of cyanoselenoacetamide
XVI, 0.83 ml of furfural IIe, 1 g of acetoacetamide
XVIII, and 0.9 ml of morpholine in 15 ml of absolute
ethanol was stirred for 15 min at 20 C under argon
and then allowed to stand at 20 C for a day. The pre-
cipitate was filtered off and washed with absolute
ethanol and hexane; yield 61%. The melting point and
1H NMR spectrum are in agreement with published
data [20].
6-Methyl-5-(2-methylphenylcarbamoyl)-4-(3-py-
ridyl)-2-Z-methylthio-3-cyanopyridines XIa and
XIb. To a stirred solution of 3.6 g of pyridinethione
X in 15 ml of DMF, we added in succession 5.6 ml
of 10% aqueous KOH and 10 mmol of appropriate
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

SYNTHESIS OF AMMONIUM 5-ARYLCARBAMOYL-4-HETERYL-6-METHYL-3-CYANO-...
455
Table 3. Mass spectra of compounds VIIIb VIIIh, IX, XIIIa XIIIi, XIVa XIVe, and XV, m/z (Irel, %)
[M]+
Other peaks
VIIIb 473 (4) 394 (5), 381 (39), 346 (18), 318 (6), 254 (10), 241 (7), 153 (11), 127 (16), 92 (15), 91 (100), 77 (4),
65 (13), 51 (5), 39 (6)
VIIIc 440 (8) 422 (41), 348 (6), 286 (11), 240 (16), 227 (10), 222 (62), 208 (11), 191 (12), 163 (12), 155 (19), 153
(57), 140 (16), 129 (30), 128 (11), 127 (100), 126 (13), 125 (29), 100 (12), 99 (17), 91 (17), 90 (28),
75 (18), 65 (18), 64 (15), 63 (29), 62 (13), 61 (7)
469 (11), 467 (11), 440 (10), 421 (28), 247 (10), 213 (32), 197 (12), 173 (98), 171 (100), 155 (15),
153 (39), 127 (24), 92 (14), 63 (18), 43 (16)
a
VIIId
VIIIe
VIIIf
a
a
411 (6), 396 (13), 363 (10), 315 (8), 287 (20), 261 (8), 241 (37), 213 (11), 199 (92), 197 (100), 171
(68), 149 (39), 134 (18), 123 (78), 108 (30), 90 (87), 80 (20), 63 (51), 51 (24), 39 (36)
396 (12), 288 (11), 262 (25), 261 (36), 260 (15), 241 (20), 149 (45), 135 (34), 123 (50), 120 (32),
119 (100), 108 (49), 106 (36), 98 (13), 97 (25), 93 (90), 92 (26), 91 (62), 80 (43), 78 (18), 77 (19), 66
(17), 65 (35), 64 (34), 63 (29), 62 (11)
VIIIg 454 (8) 455 (2) [M + 1]+, 437 (6), 409 (7), 398 (11), 397 (20), 396 (85), 315 (29), 304 (30), 288 (17), 287
(100), 285 (10), 274 (15), 273 (99), 259 (20), 258 (13), 241 (29), 155 (15), 123 (66), 108 (24), 92 (13),
78 (6), 77 (8), 65 (10)
VIIIh 544 (3) 436 (9), 411 (7), 396 (100), 364 (10), 315 (19), 287 (56), 273 (42), 259 (21), 241 (20), 215 (8), 149
(23), 133 (28), 123 (39), 106 (47), 91 (22), 77 (29), 65 (14), 43 (15)
IX
452 (48) 454 (13) [M + 2]+, 330 (100), 313 (69), 285 (24), 258 (16), 241 (13), 198 (8), 123 (9), 108 (10), 92
(14), 73 (35), 65 (19), 52 (10), 44 (41), 40 (15)
378 (9), 370 (26), 351 (14), 285 (16), 271 (9), 257 (81), 243 (32), 217 (19), 211 (36), 185 (24), 167
a
XIIIa
XIIIb
(18), 153 (62), 135 (54), 127 (70), 119 (42), 99 (18), 93 (100), 77 (34), 65 (38), 51 (16), 39 (38)
370 (4), 337 (25), 257 (11), 231 (10), 217 (34), 211 (98), 185 (24), 169 (72), 153 (57), 143 (100), 127
a
(42), 115 (69), 99 (20), 90 (25), 75 (17), 63 (24), 39 (17)
XIIIc 462 (3) 461 (5) [M 1]+, 370 (49), 335 (21), 307 (28), 243 (29), 217 (10), 127 (9), 99 (4), 91 (100), 77 (3),
65 (14), 39 (5)
a
XIIId
458 (4), 430 (6), 385 (5), 370 (69), 338 (17), 232 (19), 211 (39), 199 (80), 197 (80), 185 (16), 171
(90), 153 (100), 145 (11), 127 (72), 99 (18), 90 (74), 75 (16), 63 (49), 50 (17), 39 (28)
XIIIe 428 (4) 411 (6), 382 (5), 370 (91), 342 (10), 302 (33), 274 (21), 257 (100), 229 (18), 153 (26), 127 (56), 99
(12), 90 (10), 67 (14), 44 (15)
XIIIf 519 (3) 370 (9), 275 (8), 257 (19), 229 (5), 127 (13), 108 (19), 91 (100), 79 (12), 65 (6), 51 (5), 39 (4)
XIIIg 486 (3) 487 (4) [M + 1]+, 485 (11) [M 1]+, 359 (54), 342 (21), 331 (62), 316 (8), 303 (5), 275 (4), 257 (10),
243 (49), 229 (28), 216 (20), 185 (27), 127 (53), 107 (14), 91 (15), 77 (5), 67 (20), 57 (22), 41 (33)
XIIIh 444 (4) 445 (5) [M + 1]+, 443 (10) [M 1]+, 370 (38), 342 (11), 317 (62), 289 (42), 257 (100), 229 (18), 216
(14), 185 (13), 162 (10), 127 (31), 91 (15), 67 (18), 42 (9)
XIIIi 457 (10) 370 (42), 342 (18), 331 (65), 303 (64), 285 (12), 257 (100), 243 (39), 229 (23), 216 (15), 185 (14),
127 (28), 91 (12), 77 (5), 67 (16), 42 (9)
XIVa 500 (4) 378 (11), 366 (37), 350 (10), 333 (32), 304 (20), 285 (21), 257 (54), 243 (29), 229 (21), 211 (56), 185
(12), 167 (35), 149 (32), 135 (27), 123 (100), 106 (48), 93 (70), 77 (34), 65 (31), 51 (16), 39 (15)
XIVb 550 (3) 428 (6), 381 (7), 366 (20), 243 (12), 185 (24), 169 (100), 141 (38), 115 (27), 80 (9), 67 (7), 51 (8),
39 (7)
XIVc 457 (8) 366 (39), 335 (10), 307 (11), 243 (56), 126 (59), 108 (12), 91 (100), 77 (4), 65 (14), 51 (3), 39 (4)
a
XIVd
458 (4), 420 (9), 366 (84), 293 (22), 265 (16), 243 (42), 229 (24), 199 (20), 171 (33), 155 (89), 135
(10), 123 (100), 108 (41), 91 (22), 77 (16), 67 (19), 44 (26)
XIVe 424 (23) 366 (47), 333 (10), 302 (29), 274 (18), 257 (56), 229 (21), 217 (10), 185 (14), 149 (18), 123 (100),
108 (26), 91 (22), 77 (11), 59 (6), 44 (17)
XV
528 (12) 402 (26), 327 (6), 254 (3), 127 (5), 99 (6), 91 (100), 77 (8), 41 (4)
a
The peak is lacking.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 3 2005

456
DYACHENKO
N-Ethylmorpholinium 4-heteryl-5-carbamoyl-6-
11. Atsuyaki, A., Taizo, O., Takeshi, U., Yutaka, O.,
Chikara, F., Masahiro, W., and Kazumaza, Y., Chem.
Pharm. Bull., 1990, vol. 38, no. 9, p. 2446.
methyl-3-cyano-1,4-dihydropyridine-2-selenolates
XXa and XXb. A mixture of 1 g of acetoacetamide
XVIII, 10 mmol of appropriate aldehyde II, 1.5 g of
cyanoselenoacetamide XVI, and 10 mmol of N-ethyl-
morpholine in 15 ml of absolute ethanol was stirred
for 6 h at 20 C under Ar. The precipitate was filtered
off and washed with absolute ethanol and hexane.
12. Falcone, G., De Nardo, M.M., Cateni, F., Kuko-
wetz, W.R., and Halzmann, S., Pharm. Pharmacol.
Lett., 1997, vol. 7, no. 1, p. 21.
13. Dyachenko, V.D., Krivokolysko, S.G., and Litvi-
nov, V.P., Zh. Org. Khim., 1998, vol. 34, no. 6,
p. 927.
6-Methyl-5-carbamoyl-4-(2-thienyl)-3-cyano-2-
Z-methylseleno-1,4-dihydropyridines XXIIIa and
XXIIIb were prepared similarly to compounds VIII
starting from salts XX and alkyl halides VIIn and
VIIo.
14. Dyachenko, V.D., Krivokolysko, S.G., and Litvi-
nov, V.P., Khim. Geterotsikl. Soedin., 1997, no. 5,
p. 666.
15. Vatsuro, K.V. and Mishchenko, G.L., Imennye reaktsii
v organicheskoi khimii (Named Reactions in Organic
Chemistry), Moscow: Khimiya, 1976.
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