Fused sulfur-containing pyridine systems: 1. Synthesis and structures of tetrahydropyridothienopyridinone and tetrahydropyridothiopyranopyridinone derivatives

Article abstract of DOI:10.1023/A:1024420930528

The reactions of N-methylmorpholinium 4-aryl(hetaryl)-5-cyano-2-oxo-1,2,3, 4-tetrahydropyridine-6-thiolates with malononitrile and acetone in ethanol afforded substituted tetrahydropyridothienopyridinones. In the absence of acetone, tetrahydropyridothiopyranopyridinones were isolated as the major reaction products. The latter were also synthesized independently by the reactions of the above-mentioned thiolates with 2-amino-1,1,3-tricyanopropene. The structure of 2,4-diamino-10-(2-chlorophenyl)-3-cyano-5-immo-8-oxo-7,8,9,10- tetrahydro-51T-pyrido[2',3':2,3]thiopyrano[4,5-b]pyridme was established by X-ray diffraction analysis.

Full text of DOI:10.1023/A:1024420930528

Russian Chemical Bulletin, International Edition, Vol. 52, No. 4, pp. 969—977, April, 2003
969
Fused sulfurꢀcontaining pyridine systems
1. Synthesis and structures of tetrahydropyridothienopyridinone
and tetrahydropyridothiopyranopyridinone derivatives*
V. V. Dotsenko,aꢀ S. G. Krivokolysko,a A. N. Chernega,b and V. P. Litvinovc
aEast Ukrainian National University,
20aꢀ7 kv. Molodezhnyi, 91034 Lugansk, Ukraine.
Fax: (064 2) 41 9151. Eꢀmail: ksg@lep.lg.ua
bInstitute of Organic Chemistry, National Academy of Sciences of Ukraine,
5 ul. Murmanskaya, 02094 Kiev, Ukraine.
Fax: (044) 573 2643. Eꢀmail: iochkiev@ukrpack.net
cN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: vpl@cacr.ioc.ac.ru
The reactions of Nꢀmethylmorpholinium 4ꢀaryl(hetaryl)ꢀ5ꢀcyanoꢀ2ꢀoxoꢀ1,2,3,4ꢀtetraꢀ
hydropyridineꢀ6ꢀthiolates with malononitrile and acetone in ethanol afforded substituted
tetrahydropyridothienopyridinones. In the absence of acetone, tetrahydropyridothiopyranoꢀ
pyridinones were isolated as the major reaction products. The latter were also synthesized
independently by the reactions of the aboveꢀmentioned thiolates with 2ꢀaminoꢀ1,1,3ꢀtriꢀ
cyanopropene. The structure of 2,4ꢀdiaminoꢀ10ꢀ(2ꢀchlorophenyl)ꢀ3ꢀcyanoꢀ5ꢀiminoꢀ8ꢀoxoꢀ
7,8,9,10ꢀtetrahydroꢀ5Hꢀpyrido[2´,3´:2,3]thiopyrano[4,5ꢀb]pyridine was established by Xꢀray
diffraction analysis.
Key words: tetrahydropyridinethiolates, malononitrile, acetone, 2ꢀaminoꢀ1,1,3ꢀtricyanoꢀ
propene, multicomponent condensation, tetrahydropyridothienopyridinones, tetrahydroꢀ
pyridothiopyranopyridinones, Xꢀray diffraction analysis.
Partially hydrogenated pyridinethiones and the correꢀ
sponding thiolates belong to a class of promising organic
compounds, whose derivatives often exhibit high biologiꢀ
cal activity.1—4 Of the reactions of these compounds, oxiꢀ
dation, halogenation, and alkylation with haloalkanes and
their derivatives, which is sometimes followed by transforꢀ
mations into fused systems, have received most study.1,3—8
However, procedures for the synthesis of polycyclic sulꢀ
furꢀcontaining pyridine derivatives based on pyridineꢀ
thiones remain poorly developed. Earlier, we have been
demonstrated9 that the reactions of derivatives of ammoꢀ
nium tetrahydropyridinethiolates with malononitrile and
acetone proceeded through cascade heterocyclization to
form hydrogenated pyridothienopyridines, which is the
second example of the directed synthesis of the aboveꢀ
mentioned type of compounds.10
synthesis, and establish the structures of the reaction
products.
We have found that the reaction of tetrahydropyridineꢀ
6ꢀthiolates 1, malononitrile (2), and acetone (3) in reꢀ
fluxing EtOH serves as a general approach to the synthesis
of pyridothienopyridinones 4 (method A) (Scheme 1).
The same compounds were produced in the reactions of
precursors of thiolates 1, viz., the corresponding Michael
adducts,4,11,12 with compounds 2 and 3 (method B), as
exemplified by the transformation of known 1,3ꢀdioxaꢀ4ꢀ
cyclohexenolate 5.12 A promising approach to the syntheꢀ
sis of compounds 4 is based on the in situ generation of
Michael adduct 5 from 2ꢀchlorobenzaldehyde (6), cyanoꢀ
thioacetamide (7), and Meldrum´s acid (8) in the presꢀ
ence of Nꢀmethylmorpholine (9) followed by the reacꢀ
tions of adduct 5 (without isolation and purification) with
compounds 2 and 3 (method C). However, the method A
proved to be the procedure of choice, because it afforded
the target product in higher yield. For example, comꢀ
pound 4a 9 was prepared in 37% yield according to the
method A, whereas the methods B and C afforded 4a in
only 18.5% and 7% yields, respectively. It should be noted
that the reaction times in the last two cases were much
The aim of the present study was to perform the reacꢀ
tions of Nꢀmethylmorpholinium 4ꢀaryl(hetaryl)ꢀ5ꢀcyanoꢀ
2ꢀoxoꢀ1,2,3,4ꢀtetrahydropyridinethiolates with malonoꢀ
nitrile and acetone, examine the possibility of optimizaꢀ
tion of the reaction conditions using the multicomponent
* Dedicated to the blessed memory of Professor Yu. A. Sharanin.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 918—925, April, 2003.
1066ꢀ5285/03/5204ꢀ969 $25.00 © 2003 Plenum Publishing Corporation

970
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Dotsenko et al.
Scheme 1
1, 4
R
1, 4
R
a
2ꢀClC6H4
g
b
c
d
e
f
1ꢀnaphthyl
h
2ꢀthienyl
4ꢀEtOC6H4
i
2ꢀMeOC6H4
3,4ꢀ(MeO)2C6H3
j
3,4ꢀ(OCH2O)C6H3
2,5ꢀ(MeO)2C6H3
4ꢀMeC6H4
k
Ph
3,4,5ꢀ(MeO)3C6H2
longer. The same product can be prepared in 33% yield by
refluxing a mixture of thiolate 1a, isopropylidenemalonoꢀ
nitrile (1.5 equiv.) (10), and an excess of acetone in EtOH
(method D). It was found that refluxing of a mixture of
thiolate 1a and nitrile 10 in EtOH for 12 h did not afford
the expected thienodipyridine 4a, whereas this compound
was isolated after the addition of acetone followed by
heating for 6—7 h. Apparently, nitrile 10 is involved in
the retroꢀKnoevenagel reaction on refluxing in 96% EtOH
in the presence of bases. In this case, excess acetone can
hinder the latter reaction. Evidently, the method D has no
obvious advantages over the method A. A decrease in the
yield of the target products in the reactions involving a
larger number of components is, presumably, associated
with the fact that side processes become more probable.
We hypothesize that the first step of the process inꢀ
volves Knoevenagel condensation of nitrile 2 with acꢀ
etone giving rise to isopropylidenemalononitrile (10)
(Scheme 2), which is confirmed by the fact that the synꢀ
thesis can be carried out according to the method D.
Compound 10 subsequently reacts with salt 1 to form
dicyanoallyl derivative of pyridine (11). The formation of
the C—S bond is the key factor in this step. This mode of
formation of this bond in the synthesis of sulfides has not
been reported earlier. The closest analog of the aboveꢀ
described reaction seems to be the mechanism of formaꢀ
tion of thiols through Sꢀfunctionalization of the Me group
by thiolation with elemental sulfur in the presence of
bases.13 In particularly, this approach was used in the
syntheses of substituted thiophenes from derivatives of
methyleneꢀactive nitriles and sulfur by the modified
Gewald reaction.13,14 Apparently, pyridinethiolate 1 serves
as a synthetic analog of activated sulfur in the aboveꢀ
mentioned thiolation. However, alternative mechanisms
of formation of the C—S bond must not be ruled out.
Atmospheric oxygen can act as an oxidizer necessary for
this reaction. Although the data published in the literature
and our experimental results do not allow us to unamꢀ
biguously postulate the mechanism of formation of interꢀ
mediate 11, the generation of the latter is highly probable.
Under the reaction conditions, cascade heterocyclization
results in the Thorpe—Ziegler transformation of dicyanoꢀ
vinyl derivative 11 into thienopyridine 12, which, in turn,
is transformed into the final compound 4 as a result of the
closure of the second pyridine ring. The latter two steps
have a direct analogy in the literature,10 which is evidence
in favor of the proposed pathway of the reaction under
study.
The assumed scheme of the formation of compounds 4
is also supported by the fact that the reaction took another

Pyridothienoꢀ and pyridothiopyranopyridones
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
971
Scheme 2
Scheme 3
pathway in the absence of acetone. Refluxing of tetraꢀ
hydropyridinethiolates 1 in EtOH with a threefold excess
of nitrile 2 afforded pyridothiopyranopyridones 13 as the
major reaction products (Scheme 3, method A). Based on
the structures of the reaction products, we hypothesizes
that the initial step of the reaction involves dimerization
of nitrile 2 in a basic medium giving rise to 2ꢀaminoꢀ
1,1,3ꢀtricyanopropene (14). It was found that thiolates 1
did react with the dimer of malononitrile 14 on refluxing
in EtOH to give the same products 13 in even higher
yields (method B). In the latter case, the presence of even
a tenfold excess of acetone with respect to thiolate 1 did
not influence the direction of the reaction. The reactions
of dimer 14 with salts 1 can take two pathways. One of
them involves the attack of the 2ꢀaminoꢀ1,1,3ꢀtricyanoꢀ
propene anion on the CN group of thiolate 1 to form the
C—C bond followed by the closure of the thiopyran and
pyridine rings (path a). Another pathway involves the
nucleophilic attack of the thiolate ion on the nonꢀ
conjugated nitrile group of tricyanopropene 14 to form
the C—S bond followed by the successive closure of the
thiopyran and pyridine rings (path b). We plan to investiꢀ
gate the mechanism of this reaction in the future.
1l: R = 4ꢀMeOC6H4,
13: R = 2ꢀClC6H4 (a), 4ꢀMeOC6H4 (b), Ph (c), 3,4ꢀ(MeO)2C6H3 (d)
observed at δ 6.04—6.35, 10.91—11.13, and 2.43—2.54,
respectively (Table 1).
1
The H NMR spectra of pyridothiopyranopyridinoꢀ
nes 13 have analogous signals, viz., two doublets of douꢀ
blets for the protons of the C(9)H2 group at δ 2.48—2.92
and a doublet of doublets for the protons of C(10)H at
δ 4.92—5.29. The signal for the protons of the C(2)NH2
group is observed as a broadened singlet at δ 5.98—6.44.
The spectra of compounds 13 show three lowꢀfield sinꢀ
glets (the intensity of each singlet corresponds to 1 H).
We believe that the signal at δ 9.60—9.76 corresponds to
the imino group of the thiopyran ring (C(5)NH). By
analogy with pyridothienopyridines 4, the singlet at
δ 10.34—10.52 should be assigned to the endocyclic imino
group of the tetrahydropyridine ring. Presumably, the
strongly broadened singlet (δ 10.85) and the analogous
peak at δ 6.72—6.90 correspond to the C(4)NH2 group.
The splitting of the signal into two broadened singlets and
a substantial downfield shift of one of these singlets can be
attributed to the C(4)NH2...C(5)NH hydrogen bond,
1
The H NMR spectra of pyridothienopyridinones 4
have two doublets of doublets at δ 2.66—3.32 belonging
to C(8)H2 and a doublet of doublets at δ 4.41—5.34
assigned to C(9)H, which are characteristic of the
—CH(R)—CH2— fragment of the tetrahydropyridine
ring.15,16 A broadened singlet of the amino group, a sinꢀ
glet of the NH group, and a signal of the C(4)Me group are

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Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Dotsenko et al.
Table 1. Spectroscopic characteristics of compounds 4b—k and 13a—d
Comꢀ
pound
IR,
ν/cm–1
1H NMR,
δ (J/Hz)
2
4b
3480—3165 (NH, NH2);
2196 (CN); 1680 (C=O)
2.54 (s, 3 Н, С(4)Ме); 2.72 (br.pseudod, 1 Н, С(8)Н, J = 16.0)*; 3.32 (m,
1 Н, С(8)Н); 5.34 (br.pseudod, 1 Н, С(9)Н)*; 6.35 (br.s, 2 Н, NH2);
6.73—8.31 (m, 7 Н, Ar); 11.13 (br.s, 1 Н, NH)
4c
3550—3180 (NH, NH2);
2197, 2183 sh (CN);
1680 (C=O)
1.32 (t, 3 Н, СН3СН2, 3J = 6.9); 2.49 (s, 3 Н, С(4)Ме); 2.67 and 2.99 (both
br.pseudod, 1 H each, С(8)Н2, 2J = 16.2)*; 3.91 (q, 2 Н, СН3СН2, 3J = 6.9);
4.46 (br.pseudod, 1 Н, С(9)Н)*; 6.18 (br.s, 2 Н, NH2); 6.70 and 7.02
3
(both d, 2 H each, Ar, J = 8.3); 10.97 (br.s, 1 Н, NH)
4d
4e
3540, 3430, 3315,
3250—3150 (NH, NH2);
2198 (CN); 1692 (C=O)
2.51 (s, 3 Н, С(4)Ме); 2.76 and 3.02 (both br.pseudod, 1 H each, С(8)Н2,
2J = 16.6)*; 3.70 and 3.74 (both s, 3 H each, (МеО)2); 4.48 (br.pseudod, 1 Н,
С(9)Н)*; 6.19 (br.s, 2 Н, NH2); 6.55 and 6.70 (both d, 1 H each, Ar, 3J = 8.2);
7.02 (s, 1 Н, Ar); 10.99 (br.s, 1 Н, NH)
3465, 3345—3330,
3200 (NH, NH2); 2207,
2193 sh (CN); 1675 (C=O)
2.53 (s, 3 Н, С(4)Ме); 2.66 (br.pseudod, 1 Н, С(8)Н, 2J = 16.6)*; 2.93
3
(dd, 1 Н, С(8)Н, 2J = 16.6, J = 7.8); 3.59 and 3.86 (both s, 3 H each, (МеО)2);
4.68 (br.pseudod, 1 Н, С(9)Н)*; 6.04 (br.s, 2 Н, NH2); 6.12 (s, 1 Н, Ar);
3
6.64 and 6.82 (both d, 1 H each, Ar, J = 8.6); 10.93 (br.s, 1 Н, NH)
4f
3465, 3280, 3200 (NH, NH2);
2201 (CN); 1689 (C=O)
2.19 (s, 3 Н, МеAr); 2.43 (s, 3 Н, С(4)Ме); 2.68 and 3.00 (both br.pseudod,
1 H each, С(8)Н2, 2J = 16.0)*; 4.41 (br.pseudod, 1 Н, С(9)Н)*; 6.06 (br.s,
2 Н, NH2); 6.96 (br.s, 4 Н, Ar); 10.91 (br.s, 1 Н, NH)
4g
4h
3465, 3350—3180 (NH, NH2); 2.47 (s, 3 Н, С(4)Ме); 2.78 and 3.02 (both br.pseudod, 1 H each, С(8)Н2,
2207, 2200 sh (CN);
1690 (C=O)
2J = 16.3)*; 3.59 (s, 3 Н, MeО); 3.69 (s, 6 Н, (МеО)2); 4.45 (br.pseudod,
1 Н, С(9)Н)*; 6.28 (br.s, 2 Н, NH2); 6.56 (s, 2 Н, Ar); 11.01 (br.s, 1 Н, NH)
1.89 (s, 3 Н, СН3СООН); 2.48 (s, 3 Н, С(4)Ме); 2.80 (br.pseudod, 1 Н,
3600—3150 (NH, NH2, OH);
2197 (CN); 1700,
1680 (2 C=O)
2
С(8)Н, J = 16.3)*; 3.08 (dd, 1 Н, С(8)Н, 2J = 16.3, 3J = 7.1); 4.70
(br.pseudod, 1 Н, С(9)Н)*; 6.24 (br.s, 2 Н, NH2); 6.72 (m, 1 Н, thienyl);
6.82 (m, 1 Н, thienyl); 7.12 (m, 1 Н, thienyl); 11.03 (br.s, 1 Н, NH)**
4i
3460, 3350—3150 (NH, NH2); 2.52 (s, 3 Н, С(4)Ме); 2.67 (br.pseudod, 1 Н, С(8)Н, 2J = 16.6)*; 3.02 (dd,
2197 (CN); 1670 (C=O)
1 Н, С(8)Н, 2J = 16.6, 3J = 8.0); 3.91 (s, 3 Н, МеО); 4.72 (br.pseudod, 1 Н,
С(9)Н)*; 6.23 (br.s, 2 Н, NH2); 6.54 (d, J = 7.5), 6.72 (m), 6.96 (d, 3J = 8.1),
3
7.18 (m, 4 Н, Ar); 10.97 (br.s, 1 Н, NH)
4j
3465, 3320—3145 (NH, NH2); 2.50 (s, 3 Н, С(4)Ме); 2.67 and 2.98 (both br.pseudod, 1 H each, С(8)Н2, 2J =
2200, 2185 sh (CN);
1690 (C=O)
3420, 3340, 3240 (NH, NH2);
2204 (CN); 1675 (C=O)
16.2)*; 4.44 (br.pseudod, 1 Н, С(9)Н)*; 5.10 (br.s, 2 Н, ОСН2О); 6.25 (br.s,
2 Н, NH2); 6.53—6.73 (m, 3 Н, Ar); 11.01 (br.s, 1 Н, NH)
2.49 (s, 3 Н, С(4)Ме); 2.70 (br.pseudod, 1 Н, С(8)Н, J = 16.2)*; 3.08 (m,
2
4k
13a
1 Н, С(8)Н); 4.52 (br.pseudod, 1 Н, С(9)Н)*, 6.28 (br.s, 2 Н, NH2);
7.12—7.26 (m, 5 Н, Рh); 11.01 (br.s, 1 Н, NH)
2
2
3570—3165 (2 NH, 2 NH2);
2200, 2190 sh (CN);
1685 (C=O)
2.54 (br.pseudod, 1 Н, С(9)Н, J = 16.1)*; 2.90 (dd, 1 Н, С(9)Н, J = 16.1,
3J = 8.0)*; 5.29 (br.pseudod, 1 Н, С(10)Н)*; 5.98 (br.s, 2 Н, С(2)NH2);
6.87 (br.s, 1 Н, С(4)NH2); 6.98—7.37 (m, 4 Н, Ar); 9.76 (br.s, 1 Н, С(5)NH);
10.52 (s, 1 H, NH); 10.85 (br.s, 1 Н, C(4)NH2)
13b
13c
13d
3500, 3435, 3340, 3235
(2 NH, 2 NH2); 2194,
2179 sh (CN); 1684 (C=O)
2.57 (br.pseudod, 1 Н, С(9)Н, 2J = 17.3)*; 2.88 (dd, 1 Н, С(9)Н, 2J = 17.3,
3J = 7.1); 3.70 (s, 3 H, MeО); 4.95 (br.pseudod, 1 Н, С(10)Н)*; 6.31 (br.s,
3
2 Н, C(2)NH2); 6.73 (m, 1 Н, C(4)NH2; 2 Н, Ar); 7.12 (d, 2 Н, Ar, J = 7.0);
9.60 (br.s, 1 Н, С(5)NH); 10.34 (s, 1 H, NH); 10.85 (br.s, 1 Н, C(4)NH2)
2
3585—3150 (2 NH, 2 NH2);
2195, 2178 sh (CN);
1680 (C=O)
2.61 (br.pseudod, 1 Н, С(9)Н, J = 16.0)*; 2.92 (dd, 1 Н, С(9)Н, 2J = 16.0,
3J = 7.1); 5.01 (br.pseudod, 1 Н, С(10)Н)*; 6.36 (br.s, 2 Н, C(2)NH2);
6.90 (br.s, 1 Н, C(4)NH2); 7.12—7.23 (m, 5 Н, Рh); 9.67 (br.s, 1 Н, С(5)NH);
10.40 (s, 1 H, NH); 10.85 (br.s, 1 Н, C(4)NH2)
3590—3200 (2 NH, 2 NH2);
2190, 2183 sh (CN);
1686 (C=O)
2.48 (br.pseudod, 1 Н, С(9)Н, 2J = 16.4)*; 2.86 (dd, 1 Н, С(9)Н, 2J = 16.4,
3J = 7.1); 3.68, 3.72 (both s, 3 H each, (МеО)2); 4.92 (br.pseudod, 1 Н, С(10)Н)*;
3
6.44 (br.s, 2 Н, C(2)NH2); 6.65 (br.d, 2 Н, Ar, J = 8.2); 6.85 (br.s, 1 Н,
C(4)NH2); 6.87 (s, 1 Н, Ar); 9.66 (s, 1 Н, C(5)NH); 10.37 (s, 1 H, NH);
10.85 (br.s, 1 Н, C(4)NH2)
* The doublet of doublets is resolved as a broadened pseudodoublet due to overlapping of the signals.
** The signal for the proton of the COOH group was not observed due to the deuterium exchange.

Pyridothienoꢀ and pyridothiopyranopyridones
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
973
Table 2. Selected bond lengths (d) and bond angles (ω) in
13a•2DMF
dihedral angle is only 3.3°. By contrast, the
N(1)—C(1)—C(5) ring is substantially nonplanar and
adopts a distorted halfꢀboat conformation (for this ring,
the modified Cremer—Pople parameters17 S, θ, and ψ are
0.52, 60.0°, and 15.6°, respectively). The N(1), N(3), and
N(5) atoms in molecule 13a have a planarꢀtrigonal conꢀ
figuration (the sum of the bond angles at these atoms is
360° to within the experimental error). Due to efficient
n—π conjugation, the N(3)—C(11) and N(5)—C(9)
bond lengths (1.348(3) and 1.338(3) Å, respectively) are
substantially smaller than the length of the standard
N(sp2)—C(sp2) single bond (1.45 Å 18). The steric effects
are responsible for the virtually orthogonal arrangement of
the C(12)—C(17) benzene ring with respect to the heteroꢀ
cyclic system (the corresponding dihedral angle is 88.8°).
In the crystal of 13a•2DMF, the intermolecular
hydrogen bonds O(2)...H(1)—N(2) (O(2)...N(1),
2.823(3) Å; O(2)...H(1), 1.99(3) Å; O(2)—H(1)—N(1),
169(2)°), O(3)...H(5)—N(5) (O(3)...N(5), 3.005(3) Å;
O(3)...H(5), 2.18(3) Å; O(3)—H(5)—N(5), 158(2)°),
O(3)...H(6)—N(6) (O(3)...N(6), 3.015(3) Å; O(2)...H(1),
2.19(3) Å; O(2)—H(1)—N(1), 176(2)°), and
N(3)—H(3)...N(4) (N(3)...N(4), 3.005(3) Å; N(4)...H(3),
2.19(3) Å; N(3)—H(3)—N(4), 165(2)°) form a twoꢀdiꢀ
mensional network (Fig. 2). For reference, it should be
noted that the average O...N and N...N distances in hydroꢀ
gen bonds of the N—H...O, O—H...N, and N—H...N
types are19 2.89, 2.79, and 2.98 Å, respectively.
Bond
d/Å
Angle
ω/deg
Cl(1)—C(17) 1.738(3)
C(1)—S(1)—C(8)
C(1)—N(1)—C(2)
C(6)—N(2)—C(11) 118.81(18)
104.87(12)
123.07(19)
S(1)—C(1)
S(1)—C(8)
1.733(3)
1.779(2)
O(1)—C(2) 1.227(3)
N(1)—C(1) 1.399(3)
N(1)—C(2) 1.360(3)
N(2)—C(6) 1.346(3)
N(5)—C(9) 1.338(3)
N(6)—C(8) 1.271(3)
C(1)—C(5) 1.345(3)
C(2)—C(3) 1.495(3)
C(3)—C(4) 1.536(3)
C(4)—C(5) 1.505(3)
C(5)—C(6) 1.459(3)
C(6)—C(7) 1.405(3)
C(7)—C(8) 1.458(3)
C(7)—C(9) 1.435(3)
C(9)—C(10) 1.408(3)
C(10)—C(11) 1.398(3)
S(1)—C(1)—C(5)
N(1)—C(1)—C(5)
N(1)—C(2)—C(3)
C(2)—C(3)—C(4)
C(1)—C(5)—C(6)
N(2)—C(6)—C(7)
C(5)—C(6)—C(7)
C(6)—C(7)—C(8)
S(1)—C(8)—C(7)
124.97(16)
122.36(19)
115.72(19)
114.74(18)
122.71(19)
124.03(17)
124.13(18)
123.26(17)
119.68(16)
C(7)—C(9)—C(10) 117.62(18)
C(9)—C(10)—C(11) 120.10(18)
N(2)—C(11)—C(10) 122.19(19)
whose presence was confirmed by Xꢀray diffraction analyꢀ
sis of crystal solvate 13a•2DMF.
The selected bond lengths and bond angles in this
compound are given in Table 2. The overall view of
molecule 13a is shown in Fig. 1. The bicyclic
S(1)N(2)C(1)C(5)—C(11) system is virtually plaꢀ
nar, viz., the deviations of the atoms from the
mean plane are no larger than 0.071 Å and the
S(1)—C(1)—C(5)—C(8)/N(2)—C(6)—C(7)—C(9)—C(11)
The IR spectra of pyridothienopyridinones 4 have
characteristic stretching bands of the C(2)NH2 group and
the endocyclic imino group (3550—3145 cm–1) and abꢀ
sorption bands of the cyano and C=O groups in the reꢀ
gions of 2207—2196 and 1692—1670 cm–1, respectively.
The IR spectra of pyridothiopyranopyridinones 13 show
broad stretching bands of two amino groups and two imino
groups in the region of 3590—3150 cm–1. The absorption
bands corresponding to stretching vibrations of the cyano
C(15)
C(16)
Cl(1)
N(3)
group are observed in the region of 2200—2190 cm–1
.
N(4)
C(14)
The signals of the carbonyl group are observed at
1680—1686 cm–1 (see Table 1).
To summarize, we synthesized for the first time previꢀ
ously unknown heterocyclic systems, viz., 6,7,8,9ꢀtetraꢀ
C(11)
C(17)
C(18)
N(2)
C(12)
C(10)
C(9)
C(13)
hydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridines
and
7,8,9,10ꢀtetrahydroꢀ5Hꢀpyrido[2´,3´:2,3]thiopyraꢀ
no[4,5ꢀb]pyridines, based on Nꢀmethylmorpholinium
4ꢀaryl(hetaryl)ꢀ5ꢀcyanoꢀ2ꢀoxoꢀ1,2,3,4ꢀtetrahydropyridiꢀ
neꢀ6ꢀthiolates, malononitrile, or its derivatives. This fact
provides evidence that multicomponent cascade heteroꢀ
cyclization holds promise for the synthesis of new fused
heterocyclic systems.
C(4)
C(3)
C(6)
C(5)
N(5)
C(7)
C(2)
C(8)
C(1)
N(1)
O(1)
N(6)
S(1)
Experimental
1
Fig. 1. Overall view and atomic numbering scheme for molꢀ
ecule 13a.
The H NMR spectra were recorded on a Gemini 200 inꢀ
strument (200 MHz) in DMSOꢀd6 (for thiolates 1b—g,j,k, in a

974
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Dotsenko et al.
a
0
c
b
Fig. 2. Crystal packing of compound 13a (intermolecular hydrogen bonds are indicated by dashed lines).
DMSOꢀd6—CCl4 mixture) with Me4Si as the internal standard.
The IR spectra were measured on an IKSꢀ29 spectrophotometer
in Nujol mulls. Elemental analysis for C, H, and N was carried
out on a Perkin—Elmer C, H, Nꢀanalyser instrument. The course
of the reactions and purities of the reaction products were moniꢀ
tored by TLC on Silufol UVꢀ254 plates in the 3 : 5 acꢀ
etone—hexane system; visualization was carried out with the use
of iodine vapor. The melting points were determined on a Kofler
stage.
(both m, 4 H each, CH2NCH2 and CH2OCH2); 3.59 (m, 1 H,
C(4)H); 3.97 (q, 2 H, OCH2CH3, J = 7.0 Hz); 6.79 and 7.07
3
(both d, 2 H each, Ar, 3J = 8.6 Hz); 8.27 (br.s, 1 H, NH).
NꢀMethylmorpholinium 5ꢀcyanoꢀ4ꢀ(3,4ꢀdimethoxyphenyl)ꢀ2ꢀ
oxoꢀ1,2,3,4ꢀtetrahydropyridineꢀ6ꢀthiolate (1d). The yield was
70%. M.p. 135 °C (decomp.). Found (%): C, 58.42; H, 6.55;
N, 10.60. C19H25N3O4S. Calculated (%): C, 58.29; H, 6.44;
N, 10.73. IR, ν/cm–1: 3555—3225 (NH, NH+); 2174 (CN);
1
2
1654 (C=O). H NMR, δ: 2.38 (dd, 1 H, C(3)H, J = 15.6 Hz,
3J = 3.6 Hz); 2.67 (dd, 1 H, C(3)H, 2J = 15.6 Hz, 3J = 6.4 Hz);
2.78 (s, 3 H, NMe); 3.16 and 3.80 (both m, 4 H each, CH2NCH2
and CH2OCH2); 3.59 (pseudot, 1 H, C(4)H); 3.74 and 3.76
(both s, 3 H each, (MeO)2); 6.66—6.82 (m, 3 H, Ar); 8.10
(br.s, 1 H, NH).
NꢀMethylmorpholinium 4ꢀ(2ꢀchlorophenyl)ꢀ5ꢀcyanoꢀ2ꢀoxoꢀ
1,2,3,4ꢀtetrahydropyridineꢀ6ꢀthiolate (1a) was synthesized acꢀ
cording to a known procedure (method A).12
NꢀMethylmorpholinium 4ꢀaryl(hetaryl)ꢀ5ꢀcyanoꢀ2ꢀoxoꢀ
1,2,3,4ꢀtetrahydropyridineꢀ6ꢀthiolates 1b—g,j,k were prepared
analogously to thiolate 1a (method A),12 compounds 1i 16 and
NꢀMethylmorpholinium 5ꢀcyanoꢀ4ꢀ(2,5ꢀdimethoxyphenyl)ꢀ2ꢀ
oxoꢀ1,2,3,4ꢀtetrahydropyridineꢀ6ꢀthiolate (1e). The yield was
69.9%. M.p. 110 °C (decomp.). Found (%): C, 58.34; H, 6.51;
N, 10.58. C19H25N3O4S. Calculated (%): C, 58.29; H, 6.44;
N, 10.73. IR, ν/cm–1: 3570—3270 (NH, NH+); 2166 (CN);
20
1h,l
were synthesized according to procedures described
earlier.
NꢀMethylmorpholinium 5ꢀcyanoꢀ4ꢀ(1ꢀnaphthyl)ꢀ2ꢀoxoꢀ
1,2,3,4ꢀtetrahydropyridineꢀ6ꢀthiolate (1b). The yield was 72.4%.
M.p. 150 °C (decomp.). Found (%): C, 66.01; H, 6.19; N, 10.83.
C21H23N3O2S. Calculated (%): C, 66.12; H, 6.08; N, 11.01. IR,
ν/cm–1: 3550—3260 (NH, NH+); 2166 (CN); 1648 (C=O).
2
1668 (C=O). 1H NMR, δ: 2.32 (dd, 1 H, C(3)H, J = 16.1 Hz,
3J = 3.5 Hz); 2.64 (dd, 1 H, C(3)H, 2J = 16.1 Hz, 3J = 7.5 Hz);
2.77 (s, 3 H, NMe); 3.15 and 3.79 (both m, 4 H each, CH2NCH2
and CH2OCH2); 3.69 and 3.76 (both s, 3 H each, (MeO)2); 3.89
(dd, 1 H, C(4)H, 3J = 3.5 Hz, 3J = 7.5 Hz); 6.61—6.85 (m, 3 H,
Ar); 8.29 (br.s, 1 H, NH).
3
1H NMR, δ: 2.43 (dd, 1 H, C(3)H, 2J = 16.0 Hz, J = 3.2 Hz);
2
3
2.80 (s, 3 H, NMe); 2.93 (dd, 1 H, C(3)H, J = 16.0 Hz, J =
7.5 Hz); 3.19 and 3.78 (both m, 4 H each, CH2NCH2 and
CH2OCH2); 4.51 (m, 1 H, C(4)H); 7.34—8.11 (m, 7 H, Ar);
8.33 (br.s, 1 H, NH).
NꢀMethylmorpholinium 5ꢀcyanoꢀ2ꢀoxoꢀ4ꢀ(pꢀtolyl)ꢀ1,2,3,4ꢀ
tetrahydropyridineꢀ6ꢀthiolate (1f). The yield was 71%. M.p.
130 °C (decomp.). Found (%): C, 62.77; H, 6.82; N, 12.31.
C18H23N3O2S. Calculated (%): C, 62.58; H, 6.71; N, 12.16. IR,
ν/cm–1: 3540—3165 (NH, NH+); 2170 (CN); 1662 (C=O).
NꢀMethylmorpholinium 5ꢀcyanoꢀ4ꢀ(4ꢀethoxyphenyl)ꢀ2ꢀoxoꢀ
1,2,3,4ꢀtetrahydropyridineꢀ6ꢀthiolate (1c). The yield was 64.5%.
M.p. 120 °C (decomp.). Found (%): C, 60.90; H, 6.81; N, 11.08.
C19H25N3O3S. Calculated (%): C, 60.78; H, 6.71; N, 11.19.
IR, ν/cm–1: 3550—3250 (NH, NH+); 2173 (CN); 1661 (C=O).
2
1H NMR, δ: 2.28 (s, 3 H, MeAr); 2.40 (dd, 1 H, C(3)H, J =
16.0 Hz, 3J = 4.3 Hz); 2.69 (dd, 1 H, C(3)H, 2J = 16.0 Hz, 3J =
7.2 Hz); 2.75 (s, 3 H, NMe); 3.11 and 3.76 (both m, 4 H each,
CH2NCH2 and CH2OCH2); 3.60 (m, 1 H, C(4)H); 7.06 (br.s,
4 H, Ar); 8.23 (br.s, 1 H, NH).
3
1H NMR, δ: 1.33 (t, 3 H, OCH2CH3, J = 7.0 Hz); 2.34 (dd,
2
1 H, C(3)H, J = 16.1 Hz, 3J = 4.3 Hz); 2.69 (dd, 1 H, C(3)H,
3
2J = 16.1 Hz, J = 7.3 Hz); 2.77 (s, 3 H, NMe); 3.15 and 3.76

Pyridothienoꢀ and pyridothiopyranopyridones
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
975
NꢀMethylmorpholinium 5ꢀcyanoꢀ2ꢀoxoꢀ4ꢀ(3,4,5ꢀtrimethoxyꢀ
phenyl)ꢀ1,2,3,4ꢀtetrahydropyridineꢀ6ꢀthiolate (1g). The yield was
66.5%. M.p. 145 °C (decomp.). Found (%): C, 57.32; H, 6.37;
N, 10.08. C20H27N3O5S. Calculated (%): C, 56.99; H, 6.46;
N, 9.97. IR, ν/cm–1: 3550—3260 (NH, NH+); 2160 (CN); 1670
(C=O). H NMR, δ: 2.40 (dd, 1 H, C(3)H, J = 16.2 Hz, J =
4.8 Hz); 2.67 (dd, 1 H, C(3)H, 2J = 16.2 Hz, 3J = 7.0 Hz); 2.77
(s, 3 H, NMe); 3.15 and 3.82 (both m, 4 H each, CH2NCH2 and
CH2OCH2); 3.60 (m, 1 H, C(4)H); 3.65 (s, 3 H, MeO); 3.76 (s,
6 H, (MeO)2); 6.45 (s, 2 H, Ar); 8.19 (br.s, 1 H, NH).
for 48 h. The crystalline precipitate was filtered off and recrysꢀ
tallized from the corresponding solvent to obtain pyridoꢀ
thienopyridone 4a in a yield of 0.67 g (33%).
Recrystallization from a 1 : 1 EtOH—AcOH mixture afꢀ
forded the 1 : 1 solvate with EtOH, m.p. 283—285 °C (decomp.),
which was studied by Xꢀray diffraction analysis;9 the nonsolvated
product precipitated from AcOH, m.p. 297—298 °C. The specꢀ
troscopic characteristics and data from elemental analysis of
pyridothienopyridone 4a prepared according to the methods B,
C, and D are identical with those reported earlier.9
1
2
3
NꢀMethylmorpholinium 5ꢀcyanoꢀ4ꢀ(3,4ꢀmethylenedioxyꢀ
phenyl)ꢀ2ꢀoxoꢀ1,2,3,4ꢀtetrahydropyridineꢀ6ꢀthiolate (1j). The
yield was 79.2%. M.p. 140 °C (decomp.). Found (%): C, 57.89;
H, 5.71; N, 11.01. C18H21N3O4S. Calculated (%): C, 57.58;
H, 5.64; N, 11.19. IR, ν/cm–1: 3515—3210 (NH, NH+); 2169
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀmethylꢀ9ꢀ(1ꢀnaphthyl)ꢀ7ꢀoxoꢀ6,7,8,9ꢀ
tetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4b). The yield
was 36%. T.decomp. > 310 °C (from AcOH), yellow crystals.
Found (%): C, 68.88; H, 4.25; N, 14.48. C22H16N4OS. Calcuꢀ
lated (%): C, 68.73; H, 4.19; N, 14.57.
2ꢀAminoꢀ3ꢀcyanoꢀ9ꢀ(4ꢀethoxyphenyl)ꢀ4ꢀmethylꢀ7ꢀoxoꢀ
6,7,8,9ꢀtetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4c).
The yield was 30.4%. M.p. 262—263 °C (from EtOH—AcOH,
2 : 1), paleꢀyellow crystals. Found (%): C, 63.88; H, 4.85;
N, 14.88. C20H18N4O2S. Calculated (%): C, 63.47; H, 4.79;
N, 14.80.
2ꢀAminoꢀ3ꢀcyanoꢀ9ꢀ(3,4ꢀdimethoxyphenyl)ꢀ4ꢀmethylꢀ7ꢀoxoꢀ
6,7,8,9ꢀtetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4d).
The yield was 38%. T.decomp. > 298 °C (from EtOH—AcOH,
1 : 1), paleꢀyellow crystals. Found (%): C, 61.33; H, 4.66;
N, 14.40. C20H18N4O3S. Calculated (%): C, 60.90; H, 4.60;
N, 14.20.
2ꢀAminoꢀ3ꢀcyanoꢀ9ꢀ(2,5ꢀdimethoxyphenyl)ꢀ4ꢀmethylꢀ7ꢀoxoꢀ
6,7,8,9ꢀtetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4e).
The yield was 35%. M.p. 336—338 °C (from EtOH—AcOH,
1 : 2), paleꢀyellow crystals. Found (%): C, 61.30; H, 4.66;
N, 14.33. C20H18N4O3S. Calculated (%): C, 60.90; H, 4.60;
N, 14.20.
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀmethylꢀ7ꢀoxoꢀ9ꢀ(pꢀtolyl)ꢀ6,7,8,9ꢀtetraꢀ
hydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4f). The yield
was 34%. M.p. 288—290 °C (from EtOH—AcOH, 1 : 3), paleꢀ
yellow crystals. Found (%): C, 65.02; H, 4.70; N, 16.24.
C19H16N4OS. Calculated (%): C, 65.50; H, 4.63; N, 16.08.
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀmethylꢀ7ꢀoxoꢀ9ꢀ(3,4,5ꢀtrimethoxypheꢀ
nyl)ꢀ6,7,8,9ꢀtetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine
(4g). The yield was 28%. M.p. 276—278 °C (from AcOH), finely
crystalline white powder. Found (%): C, 59.60; H, 4.67; N, 13.31.
C21H20N4O4S. Calculated (%): C, 59.42; H, 4.75; N, 13.20.
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀmethylꢀ7ꢀoxoꢀ9ꢀ(2ꢀthienyl)ꢀ6,7,8,9ꢀ
tetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4h) (solvate
with AcOH (1 : 1)). The yield was 27%. M.p. 297—299 °C (from
AcOH), paleꢀyellow crystals. Found (%): C, 54.22; H, 4.08;
N, 14.15. C18H16N4O3S2. Calculated (%): C, 53.99; H, 4.03;
N, 13.99.
2ꢀAminoꢀ3ꢀcyanoꢀ9ꢀ(2ꢀmethoxyphenyl)ꢀ4ꢀmethylꢀ7ꢀoxoꢀ
6,7,8,9ꢀtetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4i).
The yield was 29%. M.p. 325—327 °C (from AcOH), white
powder. Found (%): C, 63.01; H, 4.47; N, 15.60. C19H16N4O2S.
Calculated (%): C, 62.62; H, 4.43; N, 15.37.
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀmethylꢀ9ꢀ(3,4ꢀmethylenedioxyphenyl)ꢀ
7ꢀoxoꢀ6,7,8,9ꢀtetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine
(4j). The yield was 30%. M.p. 276—278 °C (from AcOH—EtOH,
4 : 1), colorless crystals. Found (%): C, 60.40; H, 3.77; N, 14.84.
C19H14N4O3S. Calculated (%): C, 60.31; H, 3.73; N, 14.81.
2ꢀAminoꢀ3ꢀcyanoꢀ4ꢀmethylꢀ7ꢀoxoꢀ9ꢀphenylꢀ6,7,8,9ꢀtetraꢀ
hydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4k). The yield
1
2
(CN); 1677 (C=O). H NMR, δ: 2.31 (dd, 1 H, C(3)H, J =
15.9 Hz, 3J = 4.5 Hz); 2.68 (dd, 1 H, C(3)H, 2J = 15.9 Hz, 3J =
7.2 Hz); 2.78 (s, 3 H, NMe); 3.17 and 3.77 (both m, 4 H each,
CH2NCH2 and CH2OCH2); 3.57 (m, 1 H, C(4)H); 5.94 (br.s,
2 H, OCH2O); 6.61—6.78 (m, 3 H, Ar); 8.38 (br.s, 1 H, NH).
NꢀMethylmorpholinium 5ꢀcyanoꢀ2ꢀoxoꢀ4ꢀphenylꢀ1,2,3,4ꢀ
tetrahydropyridineꢀ6ꢀthiolate (1k). The yield was 67%. M.p.
120 °C (decomp.). Found (%): C, 61.39; H, 6.50; N, 12.76.
C17H21N3O2S. Calculated (%): C, 61.61; H, 6.39; N, 12.68. IR,
ν/cm–1: 3525—3270 (NH, NH+); 2167 (CN); 1665 (C=O).
3
1H NMR, δ: 2.36 (dd, 1 H, C(3)H, 2J = 15.9 Hz, J = 3.7 Hz);
2.72 (dd, 1 H, C(3)H, 2J = 15.9 Hz, 3J = 7.1 Hz); 2.78 (s, 3 H,
NMe); 3.16 and 3.76 (both m, 4 H each, CH2NCH2 and
CH2OCH2); 3.65 (m, 1 H, C(4)H); 7.16—7.29 (m, 5 H, Ph);
8.26 (br.s, 1 H, NH).
Synthesis of pyridothienopyridones 4a—j (general procedure).
A. A mixture of the corresponding pyridinethiolate 1 (8.2 mmol),
nitrile 2 (0.81 g, 12.3 mmol), and acetone 3 (6 mL, 82 mmol) in
EtOH (35 mL) was refluxed with stirring for 15—20 h (in the
case of 4b,g,j, for 25 h). Then the reaction mixture was kept at
∼20 °C for 48 h. The reaction product was filtered off and puriꢀ
fied by recrystallization from the corresponding solvent.
2ꢀAminoꢀ9ꢀ(2ꢀchlorophenyl)ꢀ3ꢀcyanoꢀ4ꢀmethylꢀ7ꢀoxoꢀ
6,7,8,9ꢀtetrahydropyrido[3´,2´:4,5]thieno[3,2ꢀb]pyridine (4a).
The synthesis according to the method A has been described
earlier.9
B. A mixture of Michael adduct 5 (4 g, 8.5 mmol), acetone 3
(6.3 mL, 85 mmol), and nitrile 2 (1.13 g, 17 mmol) was refluxed
in EtOH (35 mL) for 35 h and then kept at ∼20 °C for 48 h. The
precipitate that formed was filtered off and recrystallized
from AcOH to obtain pyridothienopyridone 4a in a yield of
0.58 g (18.5%).
C. A mixture of 2ꢀchlorobenzaldehyde (6) (2.27 mL,
20 mmol) and cyanothioacetamide (7) (2 g, 20 mmol) in EtOH
(70 mL) in the presence of two drops of Nꢀmethylmorpholine
(9) was stirred for 1 h. Then Meldrum´s acid (8) (2.88 g,
20 mmol) was added. NꢀMethylmorpholine (9) (3.3 mL,
30 mmol) was added dropwise with stirring. After 10 min, nitrile
2 (2.64 g, 40 mol) and acetone (3) (14.7 mL, 0.2 mol) were
added to the precipitate of the Michael adduct that formed. The
reaction mixture was refluxed for 10 days. The crystals that
precipitated were filtered off and recrystallized from AcOH to
obtain pyridothienopyridone 4a in a yield of 0.52 g (7%).
D. A mixture of thiolate 1a (2 g, 5.5 mmol), isopropylꢀ
idenemalononitrile (10) (0.87 g, 8.2 mmol), and acetone (5 mL)
in EtOH (30 mL) was refluxed for 20 h and then kept at ∼20 °C

976
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 4, April, 2003
Dotsenko et al.
was 51%. M.p. 316 °C (from EtOH—AcOH, 1 : 1), colorless
crystals. Found (%): C, 64.90; H, 4.27; N, 16.87. C18H14N4OS.
Calculated (%): C, 64.65; H, 4.22; N, 16.75.
Table 3. Principal crystallographic data and details of Xꢀray
diffraction study and refinement of compound 13a•2DMF
Synthesis of pyridothiopyranopyridones 13 (general proceꢀ
dure). A. A mixture of the corresponding thiolate 1a,l (4 mmol)
and nitrile 2 (0.79 g, 12 mmol) in EtOH (30 mL) was refluxed
for 25 h. The precipitate was filtered off and recrystallized from
the corresponding solvent.
B. A suspension of the corresponding thiolate 1a,d,k
(9 mmol) and 2ꢀaminoꢀ1,1,3ꢀtricyanopropene (14) (1.78 g,
13.5 mmol) in EtOH (35 mL) was refluxed for 15 h. The precipiꢀ
tate that formed was filtered off and recrystallized from the
corresponding solvent.
2,4ꢀDiaminoꢀ10ꢀ(2ꢀchlorophenyl)ꢀ3ꢀcyanoꢀ5ꢀiminoꢀ8ꢀ
oxoꢀ7,8,9,10ꢀtetrahydroꢀ5Hꢀpyrido[2´,3´:2,3]thiopyraꢀ
no[4,5ꢀb]pyridine (13a). The yields according to the methods A
and B were 29 and 44%, respectively. T.decomp. > 325 °C (from
AcOH—DMF, 1 : 1), yellowꢀgreen crystals. Found (%):
C, 54.75; H, 3.33; N, 21.28. C18H13ClN6OS. Calculated (%):
C, 54.48; H, 3.30; N, 21.18. MS (EI, 70 eV), m/z (Irel (%)):
396 [M]+ (100), 365 (43), 363 (82), 361 (62), 261 (60), 165 (57),
101 (47). Crystals of solvate 13a•2DMF suitable for Xꢀray difꢀ
fraction analysis were grown from DMF.
Parameter
Characteristic
Molecular formula
Molecular weight
a/Å
b/Å
c/Å
α/deg
β/deg
C24H27ClN8O3S
543.05
9.834(8)
11.451(10)
12.167(9)
83.75(8)
79.17(6)
82.09(8)
1323.9
γ/deg
V/Å3
Z
2
dcalc/g cm–3
Space group
µ/cm–1
1.36
P–1 (No. 2)
23.5
F(000)
Crystal dimensions/mm
Segment of the sphere
570.8
0.40×0.50×0.50
0 < h < 11
–13 < k < 13
–14 < l < 14
Number of reflections
measured
independent
in leastꢀsquares (I > 3σ(I ))
Rint
Number of refinable
parameters
Number of reflections
per parameter
R
2,4ꢀDiaminoꢀ3ꢀcyanoꢀ5ꢀiminoꢀ10ꢀ(4ꢀmethoxyphenyl)ꢀ8ꢀ
oxoꢀ7,8,9,10ꢀtetrahydroꢀ5Hꢀpyrido[2´,3´:2,3]thiopyraꢀ
no[4,5ꢀb]pyridine (13b). The yield according to the method A
was 25%. T.decomp. 288—291 °C (from AcOH—DMF, 1 : 1),
darkꢀyellow crystals. Found (%): C, 58.34; H, 4.15; N, 21.64.
C19H16N6O2S. Calculated (%): C, 58.15; H, 4.11; N, 21.41.
2,4ꢀDiaminoꢀ3ꢀcyanoꢀ5ꢀiminoꢀ8ꢀoxoꢀ10ꢀphenylꢀ7,8,9,10ꢀ
tetrahydroꢀ5Hꢀpyrido[2´,3´:2,3]thiopyrano[4,5ꢀb]pyridine
(13c). The yield according to the method B was 40%. M.p.
280—282 °C (from AcOH), brown crystals. Found (%): C, 59.99;
H, 3.93; N, 23.32. C18H14N6OS. Calculated (%): C, 59.66;
H, 3.89; N, 23.19.
4501
4487
4006
0.018
358
11.1
0.046
0.053
1.073
Rw
GOF
Weighting coefficients
∆ρ/e cm–3
4.47, –0.52, 2.63, –0.84
0.42/–0.55
2,4ꢀDiaminoꢀ3ꢀcyanoꢀ10ꢀ(3,4ꢀdimethoxyphenyl)ꢀ5ꢀiminoꢀ
8ꢀoxoꢀ7,8,9,10ꢀtetrahydroꢀ5Hꢀpyrido[2´,3´:2,3]thiopyraꢀ
no[4,5ꢀb]pyridine (13d). The yield according to the method B
was 53%. M.p. 284—286 °C (from AcOH), yellowꢀbrown crysꢀ
tals. Found (%): C, 57.12; H, 4.23; N, 19.98. C20H18N6O3S.
Calculated (%): C, 56.86; H, 4.29; N, 19.89. MS (EI, 70 eV),
m/z (Irel (%)): 422 [M]+ (100), 389 (46), 308 (30), 264 (27), 191
(96), 160 (20), 77 (19).
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
32063).
Xꢀray diffraction study of compound 13a was carried out on
an automated fourꢀcircle Enraf—Nonius CADꢀ4 diffractometer
(CuꢀKα radiation, the ratio between the scan rates 2θ/ω = 1.2,
References
θ
= 65°) at ∼20 °C. The structure was solved by direct methꢀ
max
ods and refined anisotropically by the fullꢀmatrix leastꢀsquares
method with the use of the CRYSTALS program package.21 All
H atoms were revealed from the difference electron density synꢀ
thesis and included in the refinement with fixed positional and
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isotropically). The absorption correction was applied using
the azimuthal scanning method.22 The Chebyshev weighting
scheme23 was used in the refinement. The selected bond lengths
and bond angles are listed in Table 2. The principal crystalloꢀ
graphic data and details of Xꢀray diffraction study and refineꢀ
ment are given in Table 3. The complete crystallographic data,
including the atomic coordinates, were deposited with the Camꢀ
bridge Structural Database.
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Received June 20, 2002;
in revised form November 28, 2002