Cross-recyclization of 4-aryl-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene: New route to 4-aryl-2-thioxo-2,5,6,7- tetrahydro-1H-[1]pyrindine-3-carbonitriles and their derivatives

Article abstract of DOI:10.1134/S1070428007020212

Reaction of 4-aryl-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene led to the formation of 4-aryl-2-thioxo-2,5,6,7- tetrahydro-1H-[1]pyrindine-3-carbonitriles used in the synthesis of substituted 2-alkylsulfanyl-4-aryl-6,7-di

Full text of DOI:10.1134/S1070428007020212

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 2, pp. 280−285. © Pleiades Publishing, Ltd. 2007.
Original Russian Text © V.D. Dyachenko, A.D. Dyachenko, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 2, pp. 286−291.
Cross-Recyclization of 4-Aryl-2,6-diamino-4H-thiopyran-3,5-
dicarbonitriles with 1-Morpholino-1-cyclopentene:
New Route to 4-Aryl-2-thioxo-2,5,6,7-tetrahydro-1H-[1]pyrindine-
3-carbonitriles and Their Derivatives
V. D. Dyachenko and A. D. Dyachenko
Taras Shevchenko National Pedagogical University, Lugansk, 91011 Ukraine
e-mail: dvd_lug@online.lg.ua
Received October 4, 2005
Abstract—Reaction of 4-aryl-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles with 1-morpholino-1-cyclopentene led
to the formation of 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1H-[1]pyrindine-3-carbonitriles used in the synthesis of
substituted 2-alkylsulfanyl-4-aryl-6,7-dihydro-5H-[1]pyrindine-3-carbonitriles and 3-amino-4-aryl-6,7-dihydro-5H-
cyclopenta[b]thieno[3,2-e]pyridines.
DOI: 10.1134/S1070428007020212
The interest of researchers to pyrindine derivatives is
aroused by discovery among them of compounds with
antiphlogistic [1], antidepressant [2], anticonvulsant [3],
and antibacterial activity [4]. The main synthetic
procedures for the pyrindine skeleton consist in the
condensation of sodium salts of cyclopentanone 2-formyl
derivatives with cyanoacetic acid chalcogenoamides [5],
recyclization of 4-amino-6-aryl-1,3-dithia-2-spirocyclo-
pentane-5-cyano-4-cyclohexenes [6], reaction of 2,5-di-
benzyldicyclopentanone with cyanothioacetamide [7],
reaction of cyclohexylidenecyanothioacetamide with
1-morpholino-1-cyclopentene [8], three-component
condensation of aldehydes with cyanoacetic acid
derivatives and cyclopentanone [9] or its enamine [10],
and reaction of cyclopentanone dithioacetal with β-lithio-
aminoacrylonitrile [11].
and D. Further treating the mixture with hydrochloric acid
provided 4-aryl-2-thioxo-2,5,6,7-tetrahydro-1H-[1]-
pyrindine-3-carbonitriles Va–Vc.
The structure of compounds Va–Vc was confirmed
by spectral data and chemical reactions. For instance,
their reaction with alkyl halides VIa, VIb, VId, VIg, VIi,
VIj, and VIl–VIn gives rise to the corresponding
thioethers VIIa–VIIi (method a) which can be obtained
in a one-pot synthesis omitting the stage of 2-thioxo-
pyrindines Va–Vc isolation (method b).
2-Alkylsulfanyl-4-aryl-6,7-dihydro-5H-[1]-pyrindine-
3-carbonitriles VIIb and VIIh were transformed by
treating with KOH into substituted 3-amino-4-aryl-6,7-
dihydro-5H-cyclopenta[b]thieno[3,2-e]-pyridines VIIIa
and VIIIb (method a), a characteristic reaction of
substituted heterocycles with the vicinal location of a nitrile
and an alkylsulfanyl groups [13]. Compounds VIIIa–
VIIId easily formed from the reaction mixture obtained
by boiling in ethanol thiopyrans Ia–Ie and enamine II, at
treating it in succession with alkyl halides VIa–VIn and
a water solution of KOH (method b).
In this study a new route was discovered leading to
compounds of these class involving a cross-recyclization
of 4-aryl-2,6-diamino-4H-thiopyran-3,5-dicarbonitriles Ia–
Ie with 1-morpholino-1-cyclopentene (II). The reaction
pathway includes apparently the opening of the thiopyran
ring giving intermediate A decomposing further into
malononitrile (III) and arylmethylenecyanothioacetamide
(IV). The latter reacts with enamine II by Stork reaction
type [12] with the formation of adduct B undergoing
intramolecular transamination and dehydration.As a result
of these processes arise the corresponding structures C
IR spectra of thioethers VIIa–VIIl contain char-
acteristic absorption bands from the stretching vibrations
of a conjugated cyano group at 2208–2222 cm–1. In going
to compounds VIIIa–VIIId these band disappear, and
appear absorption bands of stretching and bending
280

CROSS- RECYCLIZATION OF 4-ARYL-2,6-DIAMINO-4H-THIOPYRAN-3,5-DICARBONITRILES
281
Ar
N
Ar
Ar
S
O
NC
CN
NC
CN
CN
II
CN
Ar
CH2(CN)2
H2N
NH2
S
NH2
S
NH2
III
_
Ia Ie
A
IV
II
Ar
Ar
N
CN
S
CN
S
CN
S H2N
_2[H]
N
H
H2N
N
O
O
N
O
D
C
B
_
_
VIb VId, VIh, KОН
b
HCl
Ar
VIа VIn
b
Hlg
Z /KOH
Ar
N
Ar
N
NH2
S
VIа, VIb, VId, VIg,
CN
S
_
CN
KOH
VIi, VIj, VIl VIn
Z
а
а
N
H
S
Z
_
_
_
VIIIa VIIId
Va Vc
VIIа VIIl
I, V,Ar=Ph (a), 4-ClC6H4 (b), 4-BrC6H4 (c), 4-NO2C6H4 (d), 4-Me2CHC6H4 (e); VI, Hlg=Cl (a–i), Br (l–m), I (n); Z=CO2CHMe2
(a), CONHPh (b), CN (c), CO2Me (d), CO2CH2Ph (e), CO2Ph (f), CONH2 (g), 4-MeOC6H4NHCO (h), CO2Et (i), 4-ClC6H4CO (j),
2,4,5-Me3C6H2CO (k), COPh (l), CH=CH2 (m), H (n); VII, Ar=Ph (a), 4-Me2CHC6H4 (b–e), 4-ClC6H4 (f–i), 4-NO2C6H4 (j),
4-BrC6H4 (k, l); Z=CO2CHMe2 (a), CONHPh (b), 4-ClC6H4CO (c), CO2Et (d), H (e), COPh (f), CH=CH2 (g), CO2Me (h), CONH2
(i), 2,4,5-Me3C6H2CO (j), CO2Ph (k), CO2CH2Ph (l); VIII,Ar=4-Me2CHC6H4 (a, d), 4-ClC6H4 (b, c); Z=CONHPh (a), CO2Me
(b), 4-MeOC6H4NHCO (c), CN (d).
vibrations of amino group at 3195–3422 and 1640–
EXPERIMENTAL
1
1649 cm–1 respectively. In the H NMR spectra of
IR spectra were recorded on a spectrophotometer
IKS-40 from mulls in mineral oil. H NMR spectra
compounds VIIa–VIIl alongside the characteristic signals
of aromatic protons, those of the trimethylene fragment,
and Z (see EXPERIMENTAL), a signal of protons
belonging to SCH2 group appeared as a singlet in the
region δ 3.95–4.88 ppm. At the same time the signals of
SCH2 group protons disappear from the spectra of
compounds VIIIa–VIIId, and a signal of amino group
protons is present instead at δ 5.33–5.83 ppm.
Note the resistance of compounds VII and VIII
against electron impact as shown by the presence of
molecular ion peaks in their mass spectra (see
EXPERIMENTAL). Besides the numerical values of
peaks correspond to the “nitrogen rule” [14] thus
confirming the structure of compounds VII and VIII.
1
were registered on spectrometers Bruker WP-100SY
(100 MHz) (compounds VIIk and VIIl), Gemini-200
(199.975 MHz) (compound VIIa), Varian Mercury-400
(400.397 MHz) (compounds Ie and VIIj), and Bruker
DR-500 (500.13 MHz) (compounds Vc, VIIb–VIIi, and
VIIIa–VIIId) from solutions in DMSO-d6 with TMS as
an internal reference. Mass spectra were measured on
KratosMS-890 instrument (70eV) with direct admission
of samples into an ion source. Melting points were
determined on a Koeffler heating block. The reactions
progress was monitored and the purity of compounds
obtained was checked by TLC on Silufol UV-254 plates,
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V. DYACHENKO, A. DYACHENKO
282
eluent acetone–hexane, 3:5, development in iodine vapor
or under UV irradiation.
2-Isopropyloxycarbonylmethylsulfanyl-4-phenyl-
6,7-dihydro-5H-[1]pyrindine-3-carbonitrile (VIIa).
Yield 2.78 g (79%), yellow wool, mp 147°C (i-PrOH).
IR spectrum, ν, cm–1: 2218 (C≡N), 1735 (C=O). 1H NMR
spectrum, δ, ppm: 1.26 d (6H, 2Me, J 6.30 Hz), 2.09 m
(2H, C6H2), 2.83 t (2H, C5H2, J 7.24 Hz), 3.02 t (2H,
C7H2, J 7.89 Hz), 3.99 s (2H, SCH2), 4.95 m (1H,
CHMe2), 7.41–7.62 m (5H, Ph). Found,%: C 67.95;
H 5.61; N 7.82. C20H20N2O2S. Calculated,%: C 68.16;
H 5.72; N 7.95.
Substituted 4H-thiopyrans Ia–Ie were obtained by
method [15]. Compounds Ia–Ic were characterized in
[15], Id, in [16].
2,6-Diamino-4-(4-isopropylphenyl)-4H-thio-
pyran-3,5-dicarbonitrile (Ie). Yield 1.95g (81%), white
powder, mp 236–239°C (EtOH). IR spectrum, ν, cm–1:
3465, 3327, 3190 (NH2), 2200 sh (C≡N), 1650 [δ(NH2)].
1H NMR spectrum, δ, ppm: 1.24 d (6H, 2Me, J 7.12 Hz),
2.26 m (1H, CHMe2), 4.15 s (1H, H4), 6.54 br.s (4H,
2NH2), 7.16 d and 7.22 d ( 2H each, C6H4, J 7.13 Hz).
Found, %: C 64.69; H 5.28; N 18.75. C16H16N4S.
Calculated, %: C 64.84; H 5.44; N 18.90.
4-(4-Isopropylphenyl)-2-phenylcarbamoyl-
methylsulfanyl-6,7-dihydro-5H-[1]pyrindine-3-
carbonitrile (VIIb). Yield 2.99 g (70%), yellow powder,
mp 164–165°C (AcOH). IR spectrum, ν, cm–1: 2217
(C≡N), 1672 (CONH). 1H NMR spectrum, δ, ppm: 1.26
d (6H, 2Me, J 6.95 Hz), 2.07 m (2H, C6H2), 2.82 t (2H,
C5H2, J 7.18 Hz), 2.99 m (3H, C7H2 and CHMe2), 4.19 s
(2H, SCH2), 7.04 t (1H, Ph, J 6.97 Hz), 7.29 t (2H, Ph,
J 6.97 Hz), 7.41 s (4H, C6H4), 7.58 d (2H, Ph, J 7.02
Hz), 10.16 br.s (1H, NH). Mass spectrum, m/z (Irel, %):
427 (3)[M]+, 335 (100) [M –PhNH]+, 307 (34), 291 (15),
279 (10), 265 (61), 190 (11), 106 (15), 93 (38)
[PhNH2]+, 77 (26) [Ph]+, 65 (22), 43 (15). Found,%:
C 72.89; H 5.70; N 9.67. C26H25N3OS. Calculated,%:
C 73.04; H 5.89; N 9.83. M 427.
4-Aryl-2-thioxo-2,5,6,7-tetrahydro-1H-[1]pyrin-
dine-3-carbonitriles Va–Vc. A mixture of 10 mmol of
an appropriate 4H-thiopyran Ia–Ic and 1.53 g (10mmol)
of enamine II in 25 ml of anhydrous ethanol was boiled
for 5 h. On cooling the reaction mixture was diluted with
10% hydrochloric acid till pH 5 and left standing for
48 h. Then the precipitate was filtered off and washed
with ethanol and hexane.
2-Thioxo-4-phenyl-2,5,6,7-tetrahydro-1H-
[1]pyrindine-3-carbonitrile (Va). Yield 1.64 g (65%),
yellow powder, mp 240–242°C (AcOH) (239–240°C
[17]).
4-(4-Isopropylphenyl)-2-(4-chlorobenzoyl-
methylsulfanyl)-6,7-dihydro-5H-[1]pyrindine-3-
carbonitrile (VIIc). Yield 2.46 g (55%), yellow powder,
mp 123–124°C (ACOH). IR spectrum, ν, cm–1: 2215
(C≡N), 1692 (C=O). 1H NMR spectrum, δ, ppm: 1.29 d
(6H, 2Me, J 6.92 Hz), 1.98 m (2H, C6H2), 2.77 m (4H,
C5H2 and C7H2), 2.97 m (1H, CHMe2), 4.81 s (2H,
SCH2), 7.40 s (4H, C6H4), 7.61 d and 8.15 d (ïO 2H,
4-Cl6H4, J 8.57 Hz). Mass spectrum, m/z (Irel, %): 448
(4) [M + 1]+, 447 (5) [M]+, 446 (8)[M – 1]+, 445 (6)
[M – 2]+, 307 (84), 265 (26), 139 (100), 111 (32), 75 (9),
43 (5). Found,%: C 69.72; H 5.04; N 6.12. C26H23ClN2OS.
Calculated,%: C 69.86; H 5.19; N 6.27. M 447.
2-Thioxo-4-(4-chlorophenyl)-2,5,6,7-tetrahydro-
1H-[1]pyrindine-3-carbonitrile (Vb). Yield 1.72 g
(60%), yellow powder, mp 262–264°C (AcOH) (259–
261°C [17]).
4-(4-Isopropylphenyl)-2-thioxo-2,5,6,7-
tetrahydro-1H-[1]pyrindine-3-carbonitrile (Vc).
Yield 1.59 g (54%), yellow powder, mp 228–230°C
1
(AcOH). IR spectrum, ν, cm–1: 2216 (C≡N). H NMR
spectrum, δ, ppm: 1.29 d (6H, 2Me, J 6.94 Hz), 2.03 m
(2H, C6H2), 2.63 t (2H, C7H2, J 7.40 Hz), 3.03 t (2H,
C5H2, J 4.60 Hz), 7.36 s (4H, C6H4), 14.21 br.s (1H,
NH). Found,%: C 73.29; H 6.01; N 9.38. C18H18N2S.
Calculated,%: C 73.43; H 6.16; N 9.52.
4-(4-Isopropylphenyl)-2-ethoxycarbonyl-
methylsulfanyl-6,7-dihydro-5H-[1]pyrindine-3-
carbonitrile (VIId). Yield 2.09 g (57%), white powder,
mp 97–98°C (EtOH). IR spectrum, ν, cm–1: 2219 (C≡N),
4-Aryl-2-Z-methylsulfanyl-6,7-dihydro-5H-[1]-
pyrindine-3-carbonitriles VIIa–VIIi. a. To a stirred
solution of 10 mmol of an appropriate 2-thioxopyrindine
Va–Vc in 15 ml of DMF was added at 20°C in succession
5.6 ml (10 mmol) of 10% water solution of KOH and
10 mmol of an appropriate alkyl halide VIa, VIb, VId,
VIg, VIi, VIj, or VIl–VIn, the mixture was stirred for
30 min and then diluted with an equal volume of water.
The separated precipitate was filtered off, washed with
water, ethanol, and hexane.
1
1732 (C=O). H NMR spectrum, δ, ppm: 1.28 t (3H,
CH3CH2, J 6.16 Hz), 1.31 d (6H, 2Me, J 6.91 Hz),
2.07 m (2H, C6H2), 2.83 t (2H, C5H2, J 7.14 Hz), 3.02 m
(3H, C7H2 and CHMe2), 4.09 s (2H, SCH2), 4.15 q (2H,
OCH2, J 6.16 Hz), 7.42 s (4H, C6H4). Found,%: C 69.28;
H 6.11; N 7.18. C22H24N2O2S. Calculated,%: C 69.44;
H 6.36; N 7.36.
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CROSS- RECYCLIZATION OF 4-ARYL-2,6-DIAMINO-4H-THIOPYRAN-3,5-DICARBONITRILES
283
1]+, 358 (35) [M]+, 357 (66) [M – 1]+, 323 (10), 299
(100), 263 (40), 218 (19), 190 (37), 164 (20), 59 (21), 45
(14). Found,%: C 60.11; H 4.08; N 7.66. C18H15ClN2O2S.
Calculated,%: C 60.25; H 4.21; N 7.81. M 359.
4-(4-Isopropylphenyl)-2-methylsulfanyl-6,7-
dihydro-5H-[1]pyrindine-3-carbonitrile (VIIe). Yield
2.03 g (66%), yellow powder, mp 95°C (EtOH). IR
1
spectrum, ν, cm–1: 2219 (C≡N). H NMR spectrum, δ,
ppm: 1.28 d (6H, 2Me, J 6.84 Hz), 2.07 m (2H, C6H2),
2.61 s (3H, SMe), 2.82 t (2H, C5H2, J 7.17 Hz), 2.99 m
(1H, CHMe2), 3.05 t (2H, C7H2, J 7.22 Hz), 7.40 s (4H,
C6H4). Mass spectrum, m/z (Irel, %): 310 (4)[M + 2]+,
309 (13) [M + 1]+, 308 (46) [M]+, 307 (100) [M – 1]+,
277 (9), 265 (94), 190 (16), 138 (39), 115 (11), 91 (10), 77
(12), 63 (7), 41 (14). Found,%: C 73.78; H 6.42; N 8.89.
C19H20N2S. Calculated,%: C 73.99; H 6.54; N 9.08.
M 308.
2-Carbamoylmethylsulfanyl-4-(4-chlorophenyl)-
6,7-dihydro-5H-[1]pyrindine-3-carbonitrile (VIIi).
Yield 2.61 g (76%), white powder, mp 182–183°C
(EtOH). IR spectrum, ν, cm–1: 2208 (C≡N), 1692
1
(CONH2). H NMR spectrum, δ, ppm: 2.09 m (2H,
C6H2), 2.78 t (2H, C5H2, J 7.15 Hz), 3.04 t (2H, C7H2,
J 7.58 Hz), 3.95 s (2H, SCH2), 7.04 br.s and 7.96 br.s
(1H each, NH2), 7.52 d and 7.59 d (2H each, C6H4,
J 8.54 Hz). Mass spectrum, m/z (Irel, %): 345 (8)[M +
2]+, 344 (11) [M + 1]+, 343 (19) [M]+, 342 (21) [M – 1]+,
326 (10), 299 (100), 263 (25), 218 (14), 190 (27), 164
(19), 44 (23). Found,%: C 59.18; H 3.96; N 12.04.
C17H14ClN3OS. Calculated,%: C 59.39; H 4.10; N 12.22.
M 344.
2-Benzoylmethylsulfanyl-4-(4-chlorophenyl)-6,7-
dihydro-5H-[1]pyrindine-3-carbonitrile (VIIf). Yield
3.35 g (83%), yellow powder, mp 180°C (AcOH). IR
spectrum, ν, cm–1: 2222 (C≡N), 1697 (C=O). 1H NMR
spectrum, δ, ppm: 2.00 m (2H, C6H2), 2.75 t (2H, C5H2,
J 7.21 Hz), 2.84 t (2H, C7H2, J 7.15 Hz), 4.88 s (2H,
SCH2), 7.48–7.62 m (6Harom), 7.67 t (1Harom, J 6.91 Hz),
8.06 d (2Harom, J 8.54 Hz). Mass spectrum, m/z (Irel, %):
404 (5)[M]+, 299 (27), 190 (8), 105 (100) [PhCO]+, 77
(31) [Ph]+, 51 (6). Found,%: C 68.04; H 4.07; N 6.78.
C23H17ClN2OS. Calculated,%: C 68.23; H 4.23; N 6.92.
M 404.
Compounds VIIa–VIIl. b. A mixture of 10 mmol of
an appropriate 4H-thiopyran Ia–Ie and 1.53 g (10 mmol)
of enamine II in 25ml of anhydrous ethanol was boiled
for 5 h and filtered while hot through a folded paper filter.
On cooling to room temperature to the reaction mixture
was added at stirring 10 mmol of an appropriate alkyl
halide VIa–VIn, the mixture was stirred for 4 h, diluted
with an equal volume of water, and the formed precipitate
was filtered off, washed with water, ethanol, and hexane.
Compounds VIIa–VIIi are identical in melting point and
chromatographic data to those obtained by method a.
Yield 71 (a), 65 (b), 77 (c), 59 (d), 66 (e), 53 (f), 75 (g),
64 (h), 61% (i).
2-Allylsulfanyl-4-(4-chlorophenyl)-6,7-dihydro-
5H-[1]pyrindine-3-carbonitrile (VIIg). Yield 2.02 g
(62%), yellow powder, mp 99–100°C (MeOH). IR
1
spectrum, ν, cm–1: 2219 (C≡N). H NMR spectrum, δ,
ppm: 2.07 m (2H, C6H2), 2.80 t (2H, C5H2, J 7.25 Hz),
3.06 t (2H, C7H2, J 7.61 Hz), 3.95 d (2H, SCH2, J 6.55
Hz), 5.14 d (1H, =CH2, Jcis 9.56 Hz), 5.35 d (1H, =CH2,
Jtrans 17.38 Hz), 5.96 m (1H, CH=), 7.50 d and 7.58 d
(2H each, C6H4). Mass spectrum, m/z (Irel, %): 329 (8)
[M + 2]+, 328 (31) [M + 1]+, 327 (46) [M]+, 326 (84)
[M – 1]+, 325 (87) [M – 2]+, 311 (100), 293 (42), 258
(27), 218 (22), 190 (38), 177 (15), 164 (26), 138 (14), 114
(8), 71 (6), 39 (28). Found,%: C 66.01; H 4.48; N 8.42.
C18H15ClN2S. Calculated,%: C 66.15; H 4.63; N 8.57.
M 327.
2-(2,4,5-Trimethylbenzoylmethylsulfanyl)-4-(4-
nitrophenyl)-6,7-dihydro-5H-[1]pyrindine-3-
carbonitrile (VIIj). Yield 3.43 g (75%), yellow powder,
mp 155–156°C (BuOH). IR spectrum, ν, cm–1: 2220
(C≡N), 1688 (C=O). 1H NMR spectrum, δ, ppm: 2.09 m
(2H, C6H2), 2.26 s (3H, Me), 2.30 s (3H, Me), 2.34 s
(3H, Me), 2.59 t (2H, C5H2, J 7.19 Hz), 2.91 t (2H, C7H2,
J 7.61 Hz), 4.62 s (2H, SCH2), 7.00 s (1Harom), 7.68 s
(1Harom), 7.75 d and 8.38 d (2H each, C6H4, J 6.99 Hz).
Found,%: C 68.11; H 4.92; N 8.98. C26H23N3O3S.
Calculated,%: C 68.25; H 5.07; N 9.18.
2-Methoxycarbonylmethylsulfanyl-4-(4-
chlorophenyl)-6,7-dihydro-5H-[1]pyrindine-3-
carbonitrile (VIIh). Yield 2.43 g (68%), white powder,
mp 135–137°C (MeOH). IR spectrum, ν, cm–1: 2218
(C≡N), 1730 (C=O). 1H NMR spectrum, δ, ppm: 2.08 m
(2H, C6H2), 3.80 t (2H, C5H2, J 7.21 Hz), 3.02 t (2H,
C7H2, J 7.57 Hz), 3.68 s (3H, Me), 4.12 s (2H, SCH2),
7.52 d and 7.59 d (ïO 2H, C6H4, J 8.47 Hz). Mass
spectrum, m/z (Irel, %): 360 (14)[M + 2]+, 359 (28) [M +
4-(4-Bromophenyl)-2-phenoxycarbonyl-
methylsulfanyl-6,7-dihydro-5H-[1]pyrindine-3-
carbonitrile (VIIk). Yield 2.56 g (55%), white powder,
mp 190–192°C (ACOH). IR spectrum, ν, cm–1: 2212
(C≡N), 1733 (C=O). 1H NMR spectrum, δ, ppm: 1.82 m
(2H, C6H2), 2.85–3.16 m (4H, C5H2 and C7H2), 4.49 s
(2H, SCH2), 7.02–7.41 m (4Harom), 7.52–7.64 m (3Harom),
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V. DYACHENKO, A. DYACHENKO
284
7.80 d (2Harom, J 8.76 Hz). Found,%: C 59.22; H 3.46;
N 5.88. C23H17BrN2O2S. Calculated,%: C 59.36; H 3.68;
N 6.02.
H 4.08; N 7.66. C18H15ClN2O2S. Calculated,%: C 60.25;
H 4.21; N 7.81. M 359.
Compounds VIIIa–VIIId. b. A mixture of 10 mmol
of an appropriate 4H-thiopyran Ic or Ie and 1.53 g
(10 mmol) of enamine II in 25 ml of anhydrous ethanol
was boiled for 5 h and filtered while hot through a folded
paper filter. On cooling to room temperature to the
reaction mixture was added at stirring 10 mmol of an
appropriate alkyl halide VIb–VId, VIh, the mixture was
stirred for 4 h, diluted with 10 ml of DMF, and 5.6 ml
(10 mmol) of 10% water solution of KOH was added,
the stirring was continued for 2 h, and the mixture was
left standing for 24 h, then diluted with an equal volume
of water. The separated precipitate was filtered off,
washed with water, ethanol, and hexane.
2-Benzyloxycarbonylmethylsulfanyl-4-(4-
bromophenyl)-6,7-dihydro-5H-[1]pyrindine-3-
carbonitrile (VIIl). Yield 3.26 g (68%), yellow wool,
mp 185–187°C (ACOH). IR spectrum, ν, cm–1: 2220
(C≡N), 1729 (C=O). 1H NMR spectrum, δ, ppm: 2.73–
3.11 m (6H, 3CH2), 4.32 s (2H, SCH2), 5.16 s (2H,
OCH2), 7.24–7.55 m (7Harom), 7.79 d (2Harom, J 7.51 Hz).
Found,%: C 59.89; H 3.78; N 5.65. C24H19BrN2O2S.
Calculated,%: C 60.13; H 3.99; N 5.84.
3-Amino-4-aryl-6,7-dihydro-5H-cyclopenta-
[b]thieno[3,2-e]pyridines VIIIa and VIIIb a. To a
stirred solution of 10 mmol of an appropriate thioether
VIIb or VIIh in 15 ml of DMFwas gradually added at
18°C 5.6 ml (10 mmol) of 10% water solution of KOH,
the mixture was stirred for 1 h and then diluted with an
equal volume of water. The formed precipitate was
filtered off, washed with water, ethanol, and hexane.
Compounds VIIIa and VIIIb are identical in melting
point and chromatographic data to those obtained by
method a. Yield 72 and 66% respectively.
3-Amino-N-(4-methoxyphenyl)-4-(4-chloro-
phenyl)-6,7-dihydro-5H-cyclopenta[b]thieno-
[3,2-e]pyridine-2-carboxamide (VIIIc). Yield 3.05 g
(68%), yellow powder, mp 235–237°C (ACOH). IR
spectrum, ν, cm–1: 3405, 3330, 3211 (NH2), 1684
3-Amino-4-(4-isopropylphenyl)-N-phenyl-6,7-
dihydro-5H-cyclopenta[b]thieno[3,2-e]pyridine-2-
carboxamide (VIIIa). Yield 2.52 g (59%), yellow
powder, mp 244–245°C (EtOH–DMF, 1:1). IR spectrum,
ν, cm–1: 3412, 3333, 3214 (NH2), 1682 (CONH), 1645
[δ(NH2)]. 1H NMR spectrum, δ, ppm: 1.30 d (6H, 2Me,
J 6.96 Hz), 2.11 m (2H, C6H2), 2.71 t (2H, C5H2,
J 7.22 Hz), 3.00 m (1H, CHMe2), 3.09 t (2H, C7H2,
J 7.60 Hz), 5.83 br.s (2H, NH2), 7.04 t (1H, Ph,
J 6.94 Hz), 7.28 t (2H, Ph, J 6.94 Hz), 7.32 d (2H, Ph,
J 7.01 Hz), 7.43 d and 7.63 d (2H each, C6H4,
J 6.62 Hz), 9.26 br.s (1H, NH). Mass spectrum, m/z (Irel,
%): 429 (5)[M + 2]+, 428 (16) [M + 1]+, 427 (47) [M]+,
335 (100) [M – PhNH]+, 264 (38), 119 (10), 93 (18)
[PhNH2]+, 77 (6) [Ph]+, 65 (14), 43 (12). Found,%:
C 72.95; H 5.70; N 9.68. C26H25N3OS. Calculated,%:
C 73.04; H 5.89; N 9.83. M 427.
1
(CONH), 1640 [δ(NH2)]. H NMR spectrum, δ, ppm:
2.11 m (2H, C6H2), 3.34 t (2H, C5H2, J 7.17 Hz), 3.09 t
(2H, C7H2, J 7.64 Hz), 3.75 s (3H, Me), 5.78 br.s
(2H, NH2), 6.85 d and 7.52 d (2H, 4-MeOC6H4,
J 8.82 Hz), 7.42 d and 7.61 d (2H, 4-ClC6H4,
J 8.53 Hz), 9.19 br.s (1H, NH). Mass spectrum, m/z (Irel,
%): 450 (5)[M + 1]+, 449 (18) [M]+, 327 (68), 297 (7),
264 (39), 123 (100) [4-MeOC6H4NH2]+, 108 (10), 95 (8),
77 (4) [Ph]+. Found,%: C 63.88; H 4.31; N 9.12.
C24H20ClN3O2S. Calculated,%: C 64.07; H 4.48; N 9.34.
M 450.
3-Amino-4-(4-isopropylphenyl)-6,7-dihydro-5H-
cyclopenta[b]thieno[3,2-e]pyridine-2-carbonitrile
(VIIId). Yield 1.70 g (57%), yellow powder, mp 201–
203°C (ACOH). IR spectrum, ν, cm–1: 3403, 3311, 3199
(NH2), 2214 (C≡N), 1649 [δ(NH2)]. 1H NMR spectrum,
δ, ppm: 1.30 d (6H, 2Me, J 6.95 Hz), 2.10 m (2H, C6H2),
2.69 t (2H, C5H2, J 7.19 Hz), 3.02 m (1H, CHMe2),
3.08 t (2H, C7H2, J 7.61 Hz), 5.33 br.s (2H, NH2), 7.34 d
and 7.45 d (2H each C6H4, J 6.81 Hz). Mass spectrum,
m/z (Irel, %): 335 (8)[M + 2]+, 334 (25) [M + 1]+, 333
(100) [M]+, 332 (4) [M – 1]+, 318 (15), 290 (21), 159
(22), 77 (6) [Ph]+, 41 (4). Found,%: C 71.95; H 5.60; N
12.46. C20H19N3S. Calculated,%: C 72.04; H 5.74; N
12.60. M 333.
Methyl-3-amino-4-(4-chlorophenyl)-6,7-dihydro-
5H-cyclopenta[b]thieno[3,2-e]pyridine-2-
carboxamide (VIIIb). Yield 2.54 g (71%), yellow
powder, mp 235–236°C (BuOH). IR spectrum, ν, cm–1:
3422, 3312, 3195 (NH2), 1731 (C=O), 1648 [δ(NH2)].
1H NMR spectrum, δ, ppm: 2.10 m (2H, C6H2), 2.17 t
(2H, C5H2, J 7.18 Hz), 3.06 t (2H, C7H2, J 7.65 Hz), 3.76
c (3H, Me), 5.72 br.s (2H, NH2) , 7.44 d and 7.61 d (2H
each, C6H4, J 8.53 Hz). Mass spectrum, m/z (Irel, %):
360 (41)[M + 2]+, 359 (23) [M + 1]+, 358 (100) [M]+,
325 (97), 297 (32), 263 (29), 190 (18), 177 (11), 163 (17),
145 (44), 131 (42), 117 (20), 59 (8). Found,%: C 60.12;
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REFERENCES
8. Dyachenko, A.D., Desenko, S.M., and Dyachenko, V.D.,
Khim. Geterotsikl. Soedin., 2002, p. 845.
1. Galeeva, R.N., Rudometova, E.V., Gavrilov, M.Yu., Kol-
la, V.E., Kon’shin, M.E., and Nazmetdinov, F.Ya., Khim.-
Farm. Zh., 1997, vol. 31, p. 37. Galeeva, R.N., Gavrilov, M.Yu.,
Nazmetdinov, F.Ya., Kolla, V.E., and Kon’shin, M.E., Russian
Patent 2128651, 1999; Ref. Zh. Khim., 1999, 18O61P; Galee-
va, R.N., Gavrilov, M.Yu., Nazmetdinov, F.Ya., Kolla, V.E.,
and Kon’shin, M.E., Russian Patent 97110472/04, 1999;
Ref. Zh. Khim., 1999, 24O106P; Galeeva, R.N., Gavri-
lov, M.Yu., Nazmetdinov, F.Ya., Drovosekova, L.P., and Kol-
la, V.E., Khim.-Farm. Zh., 1998, vol. 32, p. 31.
9. Abdel-Latif, F.F., and Shaker, R.M. J. Chem. Res. Synop.,
1995, p. 146.
10. Dyachenko, V.D., Krivokolysko, S.G., and Litvinov, V.P.,
Khim. Geterotsikl. Soedin., 1998, p. 81.
11. Gupta, A.E., Ila, H., Junjappa, H., Tetrahedron, 1990, vol.
46, 3703.
12. Stork, G., Brizzolara,A., Landesman, H., Szmuszkovicz, J.,
and Terrell, R. J. Am. Chem. Soc., 1963, 85, 203; Stork, G.,
Briz-zolara, A., and Landesman, H.K., J. Am. Chem. Soc.,
1956, 78, p. 5128.
2. Galeeva, R.N., Atmani, R., Gavrilov, M.Yu., Nazmetdi-
nov, F.Ya., Drovosekova, L.P., Kolla, V.E., and Kon’-
shin, M.E., Khim.-Farm. Zh., 1998, vol. 32, p. 15.
3. Galeeva, R.N., Kholdeeva, V.A., Gavrilov, M.Yu., Kon’-
shin, M.E., Kolla, V.E., Drovosekova, L.P., and Nazmetdi-
nov, F.Ya., Khim.-Farm. Zh., 1996, vol. 30, p. 18.
4. Smirnova, T.A., Gavrilov, M.Yu., Voronina, E.V., and
Kon’shin, M.E., Khim.-Farm. Zh., 1998, vol. 32, p. 13.
5. Rodinovskaya, L.A., Belukhina, E.V., Shestopalov, A.M.,
and Litvinov, V.P., Izv. Akad. Nauk, Ser.Khim., 1994, p. 489;
Galeeva, R.N., Gavrilov, M.Yu., and Kon’shin, M.E., Izv.
Vuzov, Ser. Khim. i Khim. Tekhnol., 1996, 39, 7; Chem.
Abstr., 1997, vol. 126, 7959y.
6. Sharanin, Yu.A., Shestopalov, A.M., Promonenkov, V.K.,
and Rodinovskaya, L.A., Zh. Org. Khim., 1984, vol. 20,
p. 1539.
13. Babichev, F.S., Sharanin,Yu.A., Litvinov, V.P., Promonenkov,
V.K., and Volovenko, Yu.M., Vnutrimolekulyarnoe
vzaimodeistvie nitril’noi i C–H-, O–H-, i S–H-grupp (In-
termolecular Interaction of Nitril and C–H-, O–H-, and S–
H-groups), Kiev: Naukova Dumka, 1998, 500 p
14. Zaikin, V.G., Varlamov, A.V., Mikaya, A.I., and Prosta-
kov, N.S., Osnovy mass-spektroskopii organicheskikh
soedinenii (Bases of Mass-Spectrometry in Organic
Chemistry), Moscow: MAIK, “Nauka”/Interperiodika, 2001,
p. 286.
15. Sharanin, Yu.A., Shestopalov, A.M., Nesterov, V.N.,
Melenchuk, S.N., Promonenkov, V.K., Shklover, V.E.,
Struchkov, Yu.T., and Litvinov, V.P., Zh. Org. Khim., 1989,
vol. 25, p. 1323.
16. Dyachenko, V.D., Krivokolysko, S.G., Sharanin, Yu.A., and
Litvinov, V.P., Zh. Org. Khim., 1997, vol. 33, p. 1084.
17. Sharanin, Yu.A., Promonenkov, V.K., and Shestopa-
lov,A.M., Zh. Org. Khim., 1982, vol. 18, p. 1782.
7. Shestopalov, A.M., and Sharanin, Yu.A., Zh. Org. Khim.,
1986, vol. 22, p. 1231.
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