Transformations of tetrahydropyrido[4′,3′:4,5]thieno[2,3-d] pyrimidin-4(3H)-ones in the presence of alkynes bearing electron-withdrawing substituents

Article abstract of DOI:10.1007/s11172-012-0052-3

Tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines in the presence of activated alkynes were transformed into mixtures of pyrimido[5′,4′:4,5]thieno[3,2-d]azocines and spiro[pyridine-4, 5′-thieno[2,3-d]pyrimidines].

Full text of DOI:10.1007/s11172-012-0052-3

Russian Chemical Bulletin, International Edition, Vol. 61, No. 2, pp. 370—379, February, 2012
370
Transformations of tetrahydropyrido[4´,3´:4,5]thieno[2,3ꢀd]pyrimidinꢀ4(3H)ꢀ
ones in the presence of alkynes bearing electronꢀwithdrawing substituents
L. G. Voskressensky,a T. N. Borisova,a S. A. Kovaleva,a A. V. Listratova,a L. N. Kulikova,a
V. N. Khrustalev,b M. V. Ovcharov,a and A. V. Varlamova
aPeoples Friendship University of Russia,
6 ul. MiklukhoꢀMaklaya, 117198 Moscow, Russian Federation.
Fax: +7 (495) 955 0779. Eꢀmail: lvoskressensky@sci.pfu.edu.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Eꢀmail: vkh@xray.ineos.ac.ru
Tetrahydropyrido[4´,3´:4,5]thieno[2,3ꢀd]pyrimidines in the presence of activated alkynes
were transformed into mixtures of pyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocines and spiro[pyridineꢀ
4,5´ꢀthieno[2,3ꢀd]pyrimidines].
Key words: pyridothienopyrimidine, ring opening, expansion of the tetrahydropyridine
ring, pyrimidothieno[3,2ꢀd]azocine, spiro[pyridinethieno[2,3ꢀd]pyrimidine].
Tandem expansion of the tetrahydropyridine ring in
fused tetrahydropyridines under the action of activated
alkynes (containing electronꢀwithdrawing groups) can
serve as a general synthetic approach to fused azocines.
This reaction underlies efficient preparative methods for
the synthesis of tetrahydropyrrolo[2,3ꢀd]azocines,1 tetraꢀ
hydrothieno[3,2ꢀd]azocines,2 tetrahydroazocino[4,5ꢀb]ꢀ
and [5,4ꢀb]indoles,3 tetrahydropyrimido[4,5ꢀd]azocines,4
and tetrahydrobenzoazocines.5
The pathway of transformations of tetrahydropyridines
containing an aryl(hetaryl)methylamino fragment largely
depends on the electronic effects of the annulated aromatic
ring as well as on the solvent nature. Reactions of 2ꢀtriꢀ
fluoroacetamidotetrahydrothieno[2,3ꢀc]pyridines with
alkynes in methanol and acetonitrile give tetrahydroꢀ
thieno[3,2ꢀd]azocines through expansion of the tetraꢀ
hydropyridine ring.2 Annulation of the benzene ring to the
thiophene ring of tetrahydrothieno[2,3ꢀc]pyridines makes
such systems less reactive in reactions with alkynes. Benzoꢀ
thieno[2,3ꢀc]pyridines react only with dimethyl acetyleneꢀ
dicarboxylate (DMAD) in acetonitrile to give spiroꢀ
[benzothiopheneꢀ3,4´ꢀpyridines] in moderate yields.6
1ꢀAryltetrahydrobenzothieno[2,3ꢀc]pyridines react with
both DMAD and terminal alkynes (methyl propiolate and
acetylacetylene). These reactions produce mixtures of
benzothieno[3,2ꢀd]azocines, spiro[benzothiopheneꢀ3,4´ꢀ
pyridines], and various 1ꢀvinyl derivatives as a result of the
Stevens rearrangement.7 In methanol, the tetrahydroꢀ
pyridine ring undergoes opening under the action of solꢀ
vent molecules and the reaction products also include
2ꢀmethoxybenzylbenzothiophenes. In connection with
this, it was interesting to find out how annulation of the
pyrimidinꢀ4ꢀone fragment to the thiophene ring of tetꢀ
rahydrothieno[2,3ꢀc]pyridine would influence the pathꢀ
way of tandem transformations and the reactivity of the
resulting tricyclic heterocycles.
Starting from the Gewald tetrahydrothienopyridines8
1—4, triethyl orthoformate, and an arylamine, we obtained
tetrahydropyridothienopyrimidines 5—11 (Scheme 1). Pyꢀ
ridothienopyrimidines 5—7 and 9 were prepared in one
step. In the synthesis of compounds 8, 10, and 11, the
major reaction products were amidines 12—14, which were
isolated from the reaction mixtures and transformed into
target pyridothienopyrimidines 8, 10, and 11 under the
action of sodium amide in anhydrous toluene.
We studied reactions of tetrahydropyridothienopyrꢀ
imidines 5—11 with DMAD, methyl propiolate (MP),
and acetylacetylene (AA) in acetonitrile and methanol
(Scheme 2, Table 1).
It turned out that pyridothienopyrimidines 5—11 are
substantially less reactive than, and their tandem transforꢀ
mations in reactions with alkynes follow different pathꢀ
ways compared to, the corresponding substituted tetraꢀ
hydrothienopyridines.2 Compounds 5—11 react with
a 3—7ꢀfold excess of an alkyne in boiling methanol or
acetonitrile to give mixtures of spiro[pyridinethienoꢀ
[2,3ꢀd]pyrimidines] 15a—l (major products) and pyrimꢀ
idothieno[3,2ꢀd]azocines 16a—l formed by opening and
expansion of the tetrahydropyridine ring, respectively. Both
the yields of the target products and the reactivity of comꢀ
pounds 5—11 depend on the substituents in their phenyl
ring. Compounds 5 and 6 (Ar = Ph) slowly react with
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 368—377, February, 2012.
1066ꢀ5285/12/6102ꢀ370 © 2012 Springer Science+Business Media, Inc.

Transformations of pyridothienopyrimidinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
371
Scheme 1
1—4: R = Me (1), Et (2), Bn (3), Pri (4)
Product
R
Me
Et
Et
Et
Ar
Ph
Ph
Product
10
11
12
13
R
Ar
Ph
Ph
5
6
7
8
9
Bn
Pri
Et
Bn
Pri
C6H4—Clꢀp
C6H4—NO2ꢀp
C6H4—NO2ꢀp
Ph
Ph
Conditions: i. toluene, reflux; ii. NaNH2, toluene.
Et C6H4—OMeꢀo
14
Scheme 2
Product
R
Ar
X
Y
Product
R
Ar
X
Y
15, 16
a
b
c
d
e
f
Me
Et
Et
Et
Et
Et
Ph
Ph
CO2Me
CO2Me
CO2Me
H
CO2Me
CO2Me
CO2Me
CO2Me
COMe
g
h
i
j
k
l
Et
Et
Et
Et
Et
Pri
C6H4—NO2ꢀp
C6H4—NO2ꢀp
C6H4—OMeꢀo
C6H4—OMeꢀo
C6H4—OMeꢀo
Ph
H
H
CO2Me
COMe
CO2Me
CO2Me
COMe
CO2Me
C6H4—Clꢀp
C6H4—Clꢀp
C6H4—Clꢀp
CO2Me
H
H
H
C6H4—NO2ꢀp CO2Me
CO2Me
CO2Me
17, 18: X = Y = CO2Me
19: X = Y = CO2Me, Ar = C6H4—Clꢀp (a), C6H4—OMeꢀo (b); X = H, Y = CO2Me, Ar = C6H4—OMeꢀo (c)
DMAD in acetonitrile at 20 C. The reaction in boiling
acetonitrile gives a mixture we fail to separate by column
chromatography.
Reactions of compound 5 with DMAD in CH2Cl2 give
spiro compound 15a, 7ꢀvinylpyridothienopyrimidine 17
(11%), and 6ꢀhydroxymethylthienopyrimidine 18 (1%).
The formation of the last product is probably due to the
opening of the tetrahydropyridine ring under the action of
water contained in CH2Cl2. 7ꢀVinylpyridothienopyrꢀ
imidine 17 was also obtained in a reaction of compound 10
with DMAD in both roomꢀtemperature and boiling aceꢀ
tonitrile; the yields were 14 and 6%, respectively.

372
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Voskressensky et al.
Table 1. Yields of spiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrimidines]
15a—l and pyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocines 16a—l in
tandem transformations of pyridothienopyrimidines 5—11 with
activated alkynes
the exception that pyridothienopyrimidines 7 and 9 do not
react with acetylacetylene in methanol). Note that the
reactions of compounds 7 and 9 with DMAD and that of
compound 9 with methyl propiolate in boiling methanol
give the corresponding azocines and spiro compounds as
well as 6ꢀmethoxymethylthienopyrimidines 19a—c by
opening of the tetrahydropyridine ring under the action of
methanol (the yields are 7, 12, and 44%, respectively).
Compounds 5—11 in reactions with alkynes undergo
the following tandem transformations. The first step is the
formation of ammonium zwitterion A (Scheme 3), which
transforms itself into zwitterion B through the cleavage of
the C(1)—N bond. An intramolecular nucleophilic attack
of the anionic center in zwitterion B results in closure of
spiro compound 15. Azocines 16 can be produced from
both A and B by a nucleophilic attack on the C(1) atom.
The formation of 7ꢀvinylpyridothienopyrimidine 17 from
A results from dealkylation of the ammonium center.
Hydroxymethyl and methoxymethyl derivatives 18 and 19
are usual products of the decomposition of zwitterion A in
alcohols and solvents containing some water.
Comꢀ
pound
Alkyne
Solvent
(T/C)
*
Yield (%)
Azocine
Spiran
5
DMAD
MeCN
(20)
CH2Cl2
(20)
MeCN
(20)
MeCN
MeОН
MeCN
6 days
10 days
7 days
16a
( traces)
—
15a (25)
15a (11)
15b (18)
6
7
DMAD
DMAD
MP
16b (6)
65 h
30 h
21 h
16c (14) 15c (44)
16c (6)
16d
15c (24)
15d (57)
( traces)
MeОН
MeCN
MeCN
MeОН
MeCN
(20)
MeОН
MeCN
(20)
8 h
20 h
2 h
34 h
2 days
16d (11) 15d (62)
АА
DMAD
16e (7)
16f (12)
16f (14)
16g (9)
15e (37)
15f (28)
15f (17)
15g (25)
8
9
MP
The structures of spiro compounds 15a—l and azoꢀ
cines 16a—l were confirmed by spectroscopic data. Their
mass spectra show molecular ion peaks corresponding to
their molecular formulas. The IR spectra contain absorpꢀ
tion bands at 1747—1621 cm–1 (C=O stretches of the
3 h
5 days
16g (3)
16h
15g (51)
15h (9)
AA
( traces)
16i (18)
DMAD
MeCN
(20)
MeОН
13 days
71 h
15i (45)
15i (50)
1
amide, ester, and oxo groups). The H NMR spectra of
16i
spiro compounds 15a—l show two doublets at  5.02—5.33
( traces)
16j (12)
16j
2
from the methylene protons with J = 1.3—2.0 Hz. The
MP
MeCN
MeОН 122 h
20 h
15j (30)
15j (8)
1H NMR spectra of azocines 16d,e,g,h,j,k exhibit a singlet
at  7.32—7.48 from the proton of the enamine fragment.
The structure of spiro compound 15a was examined by
Xꢀray diffraction (Fig. 1). Structure 15a contains three
(dihydropyrimidine, dihydrothiophene, and tetrahydroꢀ
pyridine) rings. The dihydropyrimidine ring is virtually
planar, while the dihydrothiophene and tetrahydropyridꢀ
ine ones are in the conformations of slightly distorted
envelope (the C(2) atom deviates from the meanꢀsquare
plane of the other ring atoms by 0.397(2) Å) and sofa (the
C(5´) atom deviates from the meanꢀsquare plane of the
( traces)
AA
DMAD
MeCN
MeCN
(20)
11 h
12 days
16k (10) 15k (46)
16l (11) 15l (57)
11
  is the reaction time.
Compounds 7—9 containing a substituted phenyl group
react with alkynes in both methanol and acetonitrile more
readily and selectively than do compounds 5 and 6 (with
Scheme 3

Transformations of pyridothienopyrimidinones
C(11)
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
373
Spiro compound 15a contains the asymmetric C(3) atom.
The crystal of 15a is a racemate.
To sum up, we demonstrated that annulation of the
pyrimidine ring to thienopyridine provides a variety of
transformations of tetrahydropyridothienopyrimidines in
reactions with alkynes.
O(1´)
C(9´)
C(12)
C(10)
O(3´)
C(11´)
C(8´)
C(10´)
C(3´)
C(9)
C(4)
C(13)
C(14)
O(1)
O(2´)
N(1´)
N(5)
O(4´)
C(7´)
C(2´)
C(5´)
Experimental
C(3)
C(6´)
C(7A)
C(3A)
C(6)
N(7)
The IR spectra of the compounds obtained were recorded on
an Infralum FTꢀ801 FTIR spectrometer in KBr pellets or thin
films (for liquid samples). Mass spectra were measured on
a Finnigan MAT 95 XL GCꢀMS instrument (direct inlet probe,
EI, 70 eV). LCꢀMS spectra were recorded on a system composed
of an Agilent 1100 Series liquid chromatograph, an Agilent Techꢀ
nologies LC/MSD VL mass spectrometer (ESI, APCI, ELSD
Sedex 75). Highꢀresolution mass spectra were measured on
a JEOL JMSꢀT100LPꢀDART 100 instrument (ESI, DART).
1H and 13C NMR spectra were recorded on Bruker (400 (1H)
and 100 MHz (13C)) and JEOL JNMꢀECA 600 instruments
(600 (1H) and 150 MHz (13C)) in CDCl3 with Me4Si as the
internal standard. For TLC, Sorbfil and Silufol plates were used
(spots were visualized under UV light); for column chromatoꢀ
graphy, neutral alumina (Fluka, activity grade II, 60 mesh) and
Acros 60E silica gel (0.04—0.06 mm).
C(8)
C(2)
S(1)
Fig. 1. Molecular structure of spiro compound 15a with atomic
displacement ellipsoids (p = 40%).
other ring atoms by 0.651(2) Å), respectively. Because of
steric hindrances, the methoxycarbonyl substituent at the
C(3´) atom is coplanar with the plane of the tetrahydropyꢀ
ridine ring, while the methoxycarbonyl substituent at the
C(2´) atom is nearly perpendicular to this plane (the angle
between the corresponding planes is 84.95(6)).
The phenyl substituent makes an angle of 50.65(5)
with the plane of the dihydropyrimidine ring, which is
probably due to the intermolecular attractive interactions
n(S(1))...(C(9)—C(10)) [1 – x, 1 – y, 2 – z] (the
S(1)...C(9A) and S(1)...C(10A) distances are 3.433(2) and
3.503(2) Å, respectively). These interactions give rise to
centrosymmetric dimers in the crystal (Fig. 2). The dimers
are additionally stabilized by the intermolecular interacꢀ
tions (C(6)=N7)...(C(6)=N(7)) [1 – x, 1 – y, 2 – z]
(the C(6)...N(7A) and N(7)...C(6A) distances are 3.126(2) Å)
(Fig. 2).
Xꢀray diffraction study of compound 15a. Colorless prismatic
crystals (C22H21N3O5S, M = 439.48, 0.15Ч0.16Ч0.22 mm) are
monoclinic, space group P21/n; at 120(2) K: a = 9.7524(5) Å,
b = 9.9873(6) Å, c = 21.4410(12) Å,  = 100.494(1), V =
3
= 2053.4(2) Å , Z = 4, F(000) = 920, dcalc = 1.422 g cm–3
,
 = 0.199 mm–1. The unit cell parameters and the intensities of
22 836 reflections (5922 independent reflections, Rint = 0.028)
were measured on a Bruker SMART 1K CCD automatic difꢀ
fractometer (MoꢀK radiation, graphite monochromator,  and
 scan modes, 
= 30). The structure was solved by direct
max
methods and refined by the fullꢀmatrix leastꢀsquares method in
the anisotropic approximation for nonꢀhydrogen atoms. The hyꢀ
drogen atoms were located geometrically and refined isoꢀ
tropically with fixed coordinates (riding model) and thermal paꢀ
In the crystal, dimers are united into a 3D framework
through weak intermolecular hydrogen bonds C—H...O.
C(10A)
S(1)
N(7)
C(9A)
C(6A)
C(6)
C(9)
N(7A)
S(1A)
C(10)
Fig. 2. Centrosymmetric dimers in structure 15a (the hydrogen atoms are omitted). Attractive intermolecular interactions are indicatꢀ
ed with dashed lines.

374
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
Voskressensky et al.
rameters (Uiso(H) = 1.5Uequiv(C) for Me groups; Uiso(H) =
= 1.2Uequiv(C) for the other groups). Final residuals are R1 = 0.045
for 4792 independent reflections with I > 2(I) and wR2 = 0.121
for all independent reflections; the number of parameters reꢀ
fined is 283, GOOF = 1.003. All calculations were performed
with the SHELXTL program package.9 The tables of the atomic
coordinates, bond lengths, bond angles, and anisotropic thermal
parameters for compound 15a have been deposited with the
Cambridge Crystallographic Data Center.
1H NMR, : 1.19 (t, 3 H, N—CH2CH3, J = 7.1 Hz); 2.65 (q, 2 H,
N—CH2Me, J = 7.1 Hz); 2.82 (t, 2 H, C(6)H2, J = 5.6 Hz); 3.13
(tt, 2 H, C(5)H2, J = 5.6 Hz, J = 0.9 Hz); 3.71 (t, 2 H, C(8)H2,
J = 0.9 Hz); 3.80 (s, 3 H, Ph—OCH3); 7.05—7.09 (m, 2 H, Ph);
7.30 (dd, 1 H, Ph, J = 8.1 Hz, J = 1.7 Hz); 7.45 (dt, 1 H, Ph,
J = 8.1 Hz, J = 1.7 Hz); 7.84 (s, 1 H, C(2)H). MS, m/z (Irel (%)):
341 [M]+ (100), 340 (63), 326 (12), 285 (21), 284 (96), 253 (25),
164 (10), 134 (16), 120 (13), 107 (13), 92 (37), 91 (14), 77 (42),
64 (14), 56 (15), 42 (43).
Synthesis of tetrahydropyrido[4´,3´:4,5]thieno[2,3ꢀd]pyrꢀ
imidines 5—7 and 9 (general procedure). A solution of thieno[2,3ꢀc]ꢀ
pyridine 1 or 2 (10 mmol) and triethyl orthoformate (12 mmol)
in toluene (50 mL) was refluxed for 1.5—2 h. Then an appropriꢀ
ate aniline (50 mmol) was added and the reaction mixture was
refluxed for 4—30 h. The course of the reactions was monitored
by TLC. After the reaction was completed, the solvent was reꢀ
moved in vacuo and the residue was treated with ethyl acetate—diꢀ
ethyl ether. The resulting crystals of tetrahydropyrido[4´,3´:4,5]ꢀ
thieno[2,3ꢀd]pyrimidines 5—7 and 9 were filtered off and reꢀ
crystallized from ethyl acetate—hexane.
Synthesis of tetrahydropyrido[4´,3´:4,5]thieno[2,3ꢀd]pyrꢀ
imidines 8, 10, and 11 (general procedure). A. A solution of
thieno[2,3ꢀc]pyridine 2—4 (10 mmol) and triethyl orthoformate
(12 mmol) in toluene (50 mL) was refluxed for 1.5—2 h. Then an
appropriate aniline (50 mmol) was added and the reaction mixꢀ
ture was refluxed for 36—50 h. The course of the reactions was
monitored by TLC. The solvent was removed and the residue
was chromatographed on silica gel with ethyl acetate—hexane
(1 : 1) as an eluent for tetrahydrothieno[2,3ꢀc]pyridines 12—14
and with ethyl acetate as an eluent for tetrahydropyridoꢀ
[4´,3´:4,5]thieno[2,3ꢀd]pyrimidines 8, 10, and 11.
7ꢀMethylꢀ3ꢀphenylꢀ5,6,7,8ꢀtetrahydropyrido[4´,3´:4,5]ꢀ
thieno[2,3ꢀd]pyrimidinꢀ4(3H)ꢀone (5). Yield 67%, light yellow
crystals, m.p. 178—179 C, Rf 0.53 (Silufol, ethyl acetate).
Found (%): C, 64.78; H, 5.15; N, 14.02. C16H15N3OS. Calculatꢀ
ed (%): C, 64.62; H, 5.08; N, 14.13. IR, /cm–1: 1692 (C=O).
1H NMR, : 2.51 (s, 3 H, N—Me); 2.77 (t, 2 H, C(6)H2, J = 6.0 Hz);
3.15 (tt, 2 H, C(5)H2, J = 6.0 Hz, J = 1.7 Hz); 3.66 (t, 2 H,
C(8)H2, J = 1.7 Hz); 7.39 (d, 2 H, Ph, J = 7.2 Hz); 7.48 (t, 1 H,
Ph, J = 7.2 Hz); 7.53 (t, 2 H, Ph, J = 7.2 Hz); 7.99 (s, 1 H,
C(2)H). MS, m/z (Irel (%)): 297 [M]+ (38), 296 (18), 254 (51),
253 (15), 104 (23), 78 (10), 77 (92), 51 (21), 43 (37), 42 (100).
7ꢀEthylꢀ3ꢀphenylꢀ5,6,7,8ꢀtetrahydropyrido[4´,3´:4,5]thiꢀ
eno[2,3ꢀd]pyrimidinꢀ4(3H)ꢀone (6). Yield 52%, light yellow crysꢀ
tals, m.p. 127—129 C, Rf 0.50 (Silufol, ethyl acetate). Found
(%): C, 65.63; H, 5.40; N, 13.52. C17H17N3OS. Calculated (%):
C, 65.57; H, 5.50; N, 13.49. IR, /cm–1: 1698 (C=O). 1H NMR,
: 1.19 (t, 3 H, N—CH2CH3, J = 7.2 Hz); 2.65 (q, 2 H,
N—CH2Me, J = 7.2 Hz); 2.82 (t, 2 H, C(6)H2, J = 5.7 Hz); 3.14
(tt, 2 H, C(5)H2, J = 5.7 Hz, J = 1.7 Hz); 3.72 (t, 2 H, C(8)H2,
J = 1.7 Hz); 7.39 (d, 2 H, Ph, J = 7.0 Hz); 7.47—7.55 (m, 3 H,
Ph); 7.98 (s, 1 H, C(2)H). MS, m/z (Irel (%)): 311 [M]+ (100),
310 (35), 296 (14), 255 (20), 254 (88), 253 (18), 104 (23), 77 (95),
56 (21), 42 (61).
B. Sodium amide (6 mmol) was added at 20 C to a solution
of tetrahydrothieno[2,3ꢀc]pyridine 12—14 (5 mmol) in toluene
(20 mL). The course of the reactions was monitored by TLC.
After 24 h, the solvent was removed in vacuo. The residue was
chromatographed on silica gel with ethyl acetate as an eluent.
Tetrahydropyrido[4´,3´:4,5]thieno[2,3ꢀd]pyrimidines 8, 10, and
11 were recrystallized from hexane—ethyl acetate.
Ethyl 6ꢀethylꢀ2ꢀ[(4ꢀnitrophenyl)aminomethylideneamino]ꢀ
4,5,6,7ꢀtetrahydrothieno[2,3ꢀc]pyridineꢀ3ꢀcarboxylate (12).
Yield 51%, bright yellow crystals turning red when exposed to
light, m.p. 136—138 C, Rf 0.53 (Silufol, ethyl acetate). Found (%):
C, 56.82; H, 5.40; N, 13.83. C19H22N4O4S. Calculated (%):
C, 56.70; H, 5.51; N, 13.92. IR, /cm–1: 1658 (C=O). 1H NMR,
: 1.18 (t, 3 H, N—CH2CH3, J = 7.2 Hz); 1.38 (t, 3 H,
O—CH2CH3, J = 7.1 Hz); 2.61 (q, 2 H, N—CH2Me, J = 7.2 Hz);
2.75 (t, 2 H, C(4)H2, J = 5.8 Hz); 2.93 (t, 2 H, C(5)H2, J = 5.8 Hz);
3.67 (s, 2 H, C(7)H2); 4.35 (q, 2 H, O—CH2Me, J = 7.1 Hz);
7.15 (d, 2 H, Ph, J = 8.2 Hz); 7.95 (s, 1 H, N=CH—NH); 8.20
(d, 2 H, Ph, J = 8.2 Hz); 11.07 (br.s, 1 H, NH—Ph). MS (DART
MS), m/z: 403.1639 [M + H]+.
7ꢀEthylꢀ3ꢀ(4ꢀnitrophenyl)ꢀ5,6,7,8ꢀtetrahydropyridoꢀ
[4´,3´:4,5]thieno[2,3ꢀd]pyrimidinꢀ4(3H)ꢀone (8). The yield is 13
(step A) and 45% (step B), light yellow crystals, m.p. 177—179 C,
Rf 0.45 (Silufol, ethyl acetate). Found (%): C, 57.32; H, 4.71;
N, 15.78. C17H16N4O3S. Calculated (%): C, 57.29; H, 4.52;
3ꢀ(4ꢀChlorophenyl)ꢀ7ꢀethylꢀ5,6,7,8ꢀtetrahydropyridoꢀ
[4´,3´:4,5]thieno[2,3ꢀd]pyrimidinꢀ4(3H)ꢀone (7). Yield 53%,
light yellow crystals, m.p. 180—181 C, Rf 0.49 (Silufol, ethyl acetꢀ
ate). Found (%): C, 59.12; H, 4.60; N, 12.23. C17H16ClN3OS.
Calculated (%): C, 59.04; H, 4.66; N, 12.15. IR, /cm–1: 1691
1
N, 15.72. IR, /cm–1: 1690 (C=O). H NMR, : 1.20 (t, 3 H,
N—CH2CH3, J = 7.0 Hz); 2.66 (q, 2 H, N—CH2Me, J = 7.0 Hz);
2.84 (t, 2 H, C(6)H2, J = 5.5 Hz); 3.13 (tt, 2 H, C(5)H2,
J = 5.5 Hz, J = 0.8 Hz); 3.73 (t, 2 H, C(8)H2, J = 0.8 Hz); 7.63
(d, 2 H, Ph, J = 8.7 Hz); 7.98 (s, 1 H, C(2)H); 8.14 (d, 2 H, Ph,
J = 8.7 Hz). MS (DART MS), m/z: 357.1259 [M + H]+.
Ethyl 2ꢀanilinomethylideneaminoꢀ6ꢀbenzylꢀ4,5,6,7ꢀtetraꢀ
hydrothieno[2,3ꢀc]pyridineꢀ3ꢀcarboxylate (13). Yield 57%, yelꢀ
low oil, Rf 0.63 (Sorbfil, ethyl acetate—hexane, 1 : 1). Found (%):
C, 68.75; H, 6.14; N, 9.98. C24H25N3O2S. Calculated (%):
C, 68.71; H, 6.01; N, 10.02. IR, /cm–1: 1662 (C=O). 1H NMR,
: 1.37 (t, 3 H, O—CH2CH3, J = 7.1 Hz); 2.78 (t, 2 H, C(4)H2,
J = 5.7 Hz); 2.91 (t, 2 H, C(5)H2, J = 5.7 Hz); 3.56 (s, 2 H,
C(7)H2); 3.70 (s, 2 H, CH2Ph); 4.32 (q, 2 H, O—CH2Me,
J = 7.1 Hz); 7.06 (d, 2 H, Ph, J = 7.7 Hz); 7.12 (t, 1 H, Ph,
J = 7.7 Hz); 7.28 (t, 1 H, Ph, J = 7.1 Hz); 7.31—7.35 (m, 4 H, Ph);
1
(C=O). H NMR, : 1.20 (t, 3 H, N—CH2CH3, J = 7.1 Hz);
2.66 (q, 2 H, N—CH2Me, J = 7.1 Hz); 2.82 (t, 2 H, C(6)H2,
J = 5.8 Hz); 3.13 (tt, 2 H, C(5)H2, J = 5.8 Hz, J = 1.8 Hz); 3.72
(t, 2 H, C(8)H2, J = 1.8 Hz); 7.35 (d, 2 H, Ph, J = 8.8 Hz); 7.51
(d, 2 H, Ph, J = 8.8 Hz); 7.95 (s, 1 H, C(2)H). MS, m/z (Irel (%)):
345 [M]+ (93), 344 (45), 330 (13), 290 (48), 288 (75), 253 (10),
140 (25), 138 (85), 113 (27), 111 (100), 76 (10), 75 (16), 56 (22),
42 (87).
7ꢀEthylꢀ3ꢀ(2ꢀmethoxyphenyl)ꢀ5,6,7,8ꢀtetrahydropyridoꢀ
[4´,3´:4,5]thieno[2,3ꢀd]pyrimidinꢀ4(3H)ꢀone (9). Yield 48%,
white crystals, m.p. 166—168 C, Rf 0.48 (Silufol, ethyl acetate).
Found (%): C, 63.40; H, 5.75; N, 12.48. C18H19N3O2S. Calcuꢀ
lated (%): C, 63.32; H, 5.61; N, 12.31. IR, /cm–1: 1682 (C=O).

Transformations of pyridothienopyrimidinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
375
7.38 (d, 2 H, Ph, J = 7.7 Hz); 7.93 (s, 1 H, N=CH—NH); 10.76
(br.s, 1 H, NH—Ph). MS, m/z (Irel (%)): 419 [M]+ (94), 418
(90), 373 (13), 372 (10), 316 (19), 315 (59), 300 (28), 269 (18),
254 (18), 224 (10), 197 (37), 152 (11), 151 (12), 125 (35), 104
(19), 92 (10), 91 (100), 77 (58), 65 (10).
Rf 0.65 (Sorbfil, ethyl acetate—hexane, 1 : 1). Found (%): C, 60.27;
H, 4.70; N, 9.54. C22H21N3O5S. Calculated (%): C, 60.12; H, 4.82;
N, 9.56. IR, /cm–1: 1696, 1671, 1624 (C=O). 1H NMR, : 1.89
(dt, 1 H, C(5)H, J = 13.3 Hz, J = 3.6 Hz); 2.35 (ddd, 1 H,
C(5)H, J = 4.2 Hz, J = 11.7 Hz, J = 13.3 Hz); 2.91 (s, 3 H, N—Me);
3.16 (dt, 1 H, C(6)H, J = 12.6 Hz, J = 4.2 Hz); 3.46 (ddd, 1 H,
C(6)H, J = 3.6 Hz, J = 11.7 Hz, J = 12.6 Hz); 3.51 (s, 3 H,
CO2Me); 3.85 (s, 3 H, CO2Me); 5.24 (d, 1 H, =CH, J = 1.6 Hz);
5.30 (d, 1 H, =CH, J = 1.6 Hz); 7.32 (d, 2 H, Ph, J = 8.2 Hz);
7.43 (t, 1 H, Ph, J = 8.2 Hz); 7.48 (t, 2 H, Ph, J = 8.2 Hz); 8.02
(s, 1 H, C(2´)H). 13C NMR, : 30.3, 39.8, 44.1, 50.9, 52.5, 52.6,
95.3, 108.5, 125.3, 126.9, 129.1 (2 C), 129.4 (2 C), 136.6, 149.8,
150.3, 151.9, 154.8, 164.4, 165.9, 166.0. MS, m/z (Irel (%)): 439
[M]+ (73), 382 (29), 381 (26), 380 (100), 379 (24), 352 (19), 350
(36), 349 (24), 348 (30), 337 (30), 320 (41), 279 (28), 267 (21),
255 (18), 254 (72), 253 (31), 160 (29), 104 (55), 77 (55).
7ꢀBenzylꢀ3ꢀphenylꢀ5,6,7,8ꢀtetrahydropyrido[4´,3´:4,5]thiꢀ
eno[2,3ꢀd]pyrimidinꢀ4(3H)ꢀone (10). The yield is 14 (step A)
and 47% (step B), light yellow crystals, m.p. 133—134 C, Rf 0.51
(Sorbfil, ethyl acetate—hexane, 1 : 1). Found (%): C, 70.53;
H, 5.21; N, 11.32. C22H19N3OS. Calculated (%): C, 70.75;
1
H, 5.13; N, 11.25. IR, /cm–1: 1682 (C=O). H NMR, : 2.87
(t, 2 H, C(6)H2, J = 5.7 Hz); 3.14 (tt, 2 H, C(5)H2, J = 5.7 Hz,
J = 1.7 Hz); 3.70 (t, 2 H, C(8)H2, J = 1.7 Hz); 3.75 (s, 2 H,
CH2Ph); 7.32—7.40 (m, 7 H, Ph); 7.48—7.56 (m, 3 H, Ph); 7.98
(s, 1 H, C(2)H). MS (DART MS), m/z: 374.09 [M + H]+.
Ethyl 2ꢀanilinomethylideneaminoꢀ6ꢀisopropylꢀ4,5,6,7ꢀtetraꢀ
hydrothieno[2,3ꢀc]pyridineꢀ3ꢀcarboxylate (14). Yield 60%, light
yellow oil, Rf 0.55 (Silufol, ethyl acetate). Found (%): C, 64.72;
H, 6.89; N, 11.25. C20H25N3O2S. Calculated (%): C, 64.66;
Dimethyl 1ꢀethylꢀ6´ꢀmethylideneꢀ4´ꢀoxoꢀ3´ꢀphenylꢀ3´,4´,
5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrimidꢀ
ine]ꢀ2,3ꢀdicarboxylate (15b). Yield 18%, white crystals, m.p.
163—164 C, Rf 0.56 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 61.05; H, 5.24; N, 9.15. C23H23N3O5S. Calculatꢀ
ed (%): C, 60.91; H, 5.11; N, 9.27. IR, /cm–1: 1747, 1678
1
H, 6.78; N, 11.31. IR, /cm–1: 1687 (C=O). H NMR, : 1.14
(d, 6 H, N—CH(CH3)2, J = 6.5 Hz); 1.37 (t, 3 H, O—CH2CH3,
J = 7.1 Hz); 2.78 (t, 2 H, C(4)H2, J = 5.8 Hz); 2.88—2.92
(m, 3 H, N—CHMe2, C(5)H2); 3.65 (s, 2 H, C(7)H2); 4.33
(q, 2 H, O—CH2Me, J = 7.1 Hz); 7.07 (d, 2 H, Ph, J = 7.8 Hz);
7.12 (t, 1 H, Ph, J = 7.8 Hz); 7.30 (t, 2 H, Ph, J = 7.8 Hz); 7.93
(s, 1 H, N=CH—NH); 10.79 (br.s, 1 H, NH—Ph). MS (DART
MS), m/z: 372.1749 [M + H]+.
7ꢀIsopropylꢀ3ꢀphenylꢀ5,6,7,8ꢀtetrahydropyrido[4´,3´:4,5]ꢀ
thieno[2,3ꢀd]pyrimidinꢀ4(3H)ꢀone (11). The yield is 5 (step A)
and 37% (step B), light yellow crystals, m.p. 158—160 C, Rf 0.48
(Silufol, ethyl acetate). Found (%): C, 66.25; H, 5.95; N, 13.02.
C18H19N3OS. Calculated (%): C, 66.43; H, 5.88; N, 12.91. IR,
/cm–1: 1681 (C=O). 1H NMR, : 1.15 (d, 6 H, N—CH(CH3)2,
J = 7.1 Hz); 2.84 (t, 2 H, C(6)H2, J = 5.7 Hz); 2.97 (sept, 1 H,
N—CHMe2, J = 7.1 Hz); 3.11 (tt, 2 H, C(5)H2, J = 5.7 Hz,
J = 1.8 Hz); 3.80 (t, 2 H, C(8)H2, J = 1.8 Hz); 7.38 (d, 2 H, Ph,
J = 8.1 Hz); 7.47 (t, 1 H, Ph, J = 8.1 Hz); 7.52 (t, 2 H, Ph,
J = 8.1 Hz); 7.98 (s, 1 H, C(2)H). MS (DART MS), m/z:
326.1347 [M + H]+.
Reactions of tetrahydropyrido[4´,3´:4,5]thieno[2,3ꢀd]pyrꢀ
imidines with alkynes (general procedure). A solution of pyridoꢀ
thienopyrimidine 5—11 (1 mmol) and DMAD, methyl propiolꢀ
ate, or acetylacetylene (3 mmol) in methanol (30 mL) or acetoꢀ
nitrile (30 mL) was kept at 20 C or refluxed until the reaction
was completed (monitoring by TLC). The solvent was removed
and the residue was chromatographed on silica gel. The comꢀ
pounds eluted (in the order of effluence) were 6ꢀmethoxymethꢀ
ylthienopyrimidines 19a—c, azocines 16a—l*, and spiro comꢀ
pounds 15a—l. The products obtained from compound 5 and
DMAD in CH2Cl2 were eluted in the following order: thienoꢀ
pyrimidine 18, pyridothienopyrimidine 17, and spiro compound
15a. Compounds 15—19 were recrystallized from hexane—ethyl
acetate.
1
(C=O). H NMR, : 1.18 (t, 3 H, J = 7.1 Hz, N—CH2CH3);
1.89 (td, 1 H, C(5)H, J = 13.1 Hz, J = 3.3 Hz); 2.32 (ddd, 1 H,
C(5)H, J = 13.1 Hz, J = 11.6 Hz, J = 4.2 Hz); 3.10—3.22 (m, 3 H,
C(6)H, N—CH2Me); 3.48—3.55 (m, 4 H, C(6)H, CO2Me); 3.79
(s, 3 H, CO2Me); 5.16 (d, 1 H, =CH, J = 1.4 Hz); 5.24 (d, 1 H,
=CH, J = 1.4 Hz); 7.31 (d, 2 H, Ph, J = 8.1 Hz); 7.40—7.49
(m, 3 H, Ph); 8.01 (s, 1 H, C(2´)H). 13C NMR, : 13.7, 29.9,
40.8, 48.1, 51.0, 52.7, 53.0, 94.9, 108.8, 125.6, 127.0 (2 C), 129.2,
129.5 (2 C), 136.8, 149.9, 150.0, 151.9, 154.8, 164.3, 166.0, 166.1.
MS, m/z (Irel (%)): 453 [M]+ (20), 394 (18), 388 (17), 381 (13),
380 (93), 362 (95), 361 (15), 333 (21), 306 (10), 280 (13), 279
(23), 278 (10), 245 (10), 207 (14), 104 (64), 91 (11), 77 (100), 69
(12), 59 (35), 44 (22).
Dimethyl 3´ꢀ(4ꢀchlorophenyl)ꢀ1ꢀethylꢀ6´ꢀmethylideneꢀ4´ꢀ
oxoꢀ3´,4´,5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]ꢀ
pyrimidine]ꢀ2,3ꢀdicarboxylate (15c). The yield was 44 (the reacꢀ
tion in MeCN) and 24% (in MeOH), light yellow crystals, m.p.
172—174 C, Rf 0.44 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 56.68; H, 4.37; N, 8.79. C23H22ClN3O5S. Calcuꢀ
lated (%): C, 56.61; H, 4.54; N, 8.61. IR, /cm–1: 1745, 1679
1
(C=O). H NMR, : 1.19 (t, 3 H, N—CH2CH3, J = 7.1 Hz);
1.88 (td, 1 H, C(5)H, J = 13.2 Hz, J = 3.5 Hz); 2.29 (ddd, 1 H,
C(5)H, J = 13.2 Hz, J = 11.9 Hz, J = 4.4 Hz); 3.12—3.23 (m, 3 H,
C(6)H, N—CH2Me); 3.48—3.55 (m, 4 H, C(6)H, CO2Me); 3.86
(s, 3 H, CO2Me); 5.23 (d, 1 H, =CH, J = 1.8 Hz); 5.31 (d, 1 H,
=CH, J = 1.8 Hz); 7.27 (d, 2 H, Ph, J = 8.7 Hz); 7.45 (d, 2 H,
Ph, J = 8.7 Hz); 7.98 (s, 1 H, C(2´)H). 13C NMR, : 13.6, 30.0,
40.8, 48.0, 50.9, 52.6, 52.9, 108.8, 125.5, 128.3 (2 C), 129.6
(2 C), 135.1, 135.3, 144.9, 149.3, 150.0, 151.7, 154.6, 164.5,
165.9, 166.0. MS (DART MS), m/z: 488.09 [M + H]+.
Methyl 3´ꢀ(4ꢀchlorophenyl)ꢀ1ꢀethylꢀ6´ꢀmethylideneꢀ4´ꢀoxoꢀ
3´,4´,5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrꢀ
imidine]ꢀ3ꢀcarboxylate (15d). The yield was 57 (the reaction in
MeCN) and 62% (in MeOH), white crystals, m.p. 199—200 C,
Rf 0.45 (Sorbfil, ethyl acetate—hexane, 1 : 1). Found (%):
C, 58.71; H, 4.73; N, 9.76. C21H20ClN3O3S. Calculated (%):
C, 58.67; H, 4.69; N, 9.77. IR, /cm–1: 1674, 1616 (C=O).
1H NMR, : 1.20 (t, 3 H, N—CH2CH3, J = 7.2 Hz); 1.85 (td, 1 H,
C(5)H, J = 13.1 Hz, J = 3.4 Hz); 2.29 (ddd, 1 H, C(5)H,
Dimethyl 1ꢀmethylꢀ6´ꢀmethylideneꢀ4´ꢀoxoꢀ3´ꢀphenylꢀ3´,4´,
5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrimidꢀ
ine]ꢀ2,3ꢀdicarboxylate (15a). The yield was 25 (the reaction in
MeCN) and 11% (in CH2Cl2), colorless crystals, m.p. 216—218 C,
* Compounds 16a,h were not isolated in the individual state;
1
they were detected in the reaction mixtures by H NMR specꢀ
troscopy.

376
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
Voskressensky et al.
J = 13.1 Hz, J = 11.7 Hz, J = 4.7 Hz); 3.07—3.09 (m, 1 H,
C(6)H); 3.25 (q, 2 H, N—CH2Me, J = 7.2 Hz); 3.39 (ddd, 1 H,
C(6)H, J = 12.9 Hz, J = 11.7 Hz, J = 3.4 Hz); 3.56 (s, 3 H,
CO2Me); 5.15 (d, 1 H, =CH, J = 2.0 Hz); 5.29 (d, 1 H, =CH,
J = 2.0 Hz); 7.29 (d, 2 H, Ph, J = 8.7 Hz); 7.43 (d, 2 H, Ph,
J = 8.7 Hz); 7.65 (s, 1 H, C(2)H); 7.99 (s, 1 H, C(2´)H).
13C NMR, : 13.7, 30.4, 39.5, 50.3, 50.6, 52.3, 108.0, 125.3,
128.1 (2 C), 129.4 (2 C), 135.0 (2 C), 144.9, 146.3, 149.1, 152.4,
154.7, 164.8, 166.6. MS (DART MS), m/z: 430.09 [M + H]+.
3ꢀAcetylꢀ3´ꢀ(4ꢀchlorophenyl)ꢀ1ꢀethylꢀ6´ꢀmethylideneꢀ5,6ꢀ
dihydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrimidin]ꢀ4´(3´H)ꢀ
one (15e). Yield 37%, white crystals, m.p. 232—234 C, Rf 0.50
(Sorbfil, ethyl acetate). Found (%): C, 60.78; H, 4.95; N, 10.12.
C21H20ClN3O2S. Calculated (%): C, 60.94; H, 4.87; N, 10.15.
IR, /cm–1: 1674 (C=O). 1H NMR, : 1.25 (t, 3 H, N—CH2CH3,
J = 7.2 Hz); 1.85 (td, 1 H, C(5)H, J = 13.2 Hz, J = 3.6 Hz); 2.11
(s, 3 H, COMe); 2.26 (ddd, 1 H, C(5)H, J = 13.2 Hz, J = 11.9 Hz,
J = 4.5 Hz); 3.12—3.14 (m, 1 H, C(6)H); 3.30 (q, 2 H,
N—CH2Me, J = 7.2 Hz); 3.43 (ddd, 1 H, C(6)H, J = 12.6 Hz,
J = 11.9 Hz, J = 3.6 Hz); 5.02 (d, 1 H, =CH, J = 1.5 Hz); 5.22
(d, 1 H, =CH, J = 1.5 Hz); 7.29 (d, 2 H, Ph, J = 8.7 Hz); 7.43
(d, 2 H, Ph, J = 8.7 Hz); 7.47 (s, 1 H, C(2)H); 7.96 (s, 1 H,
C(2´)H). 13C NMR, : 13.8, 24.1, 30.4, 39.8, 51.0, 52.2, 106.9,
125.7, 128.2 (2 C), 129.4 (2 C), 135.0, 135.2, 144.9, 147.7, 148.9,
152.4, 154.7, 164.8, 191.0. MS (DART MS), m/z: 414.1023
[M + H]+.
3ꢀAcetylꢀ1ꢀethylꢀ6´ꢀmethylideneꢀ3´ꢀ(4ꢀnitrophenyl)ꢀ5,6ꢀdiꢀ
hydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrimidin]ꢀ4´(3´H)ꢀ
one (15h). Yield 9%, white crystals, m.p. 255—257 C, Rf 0.54
(Sorbfil, ethyl acetate). Found (%): C, 59.48; H, 4.90; N, 13.19.
C21H20N4O4S. Calculated (%): C, 59.42; H, 4.75; N, 13.20. IR,
1
/cm–1: 1674 (C=O). H NMR, : 1.26 (t, 3 H, N—CH2CH3,
J = 7.2 Hz); 1.88 (td, 1 H, C(5)H, J = 13.3 Hz, J = 3.5 Hz); 2.13
(s, 3 H, COMe); 2.25 (ddd, 1 H, C(5)H, J = 13.3 Hz, J = 11.7 Hz,
J = 4.5 Hz); 3.14 (dt, 1 H, C(6)H, J = 12.7 Hz, J = 4.5 Hz);
3.29—3.36 (m, 2 H, N—CH2Me); 3.46 (ddd, 1 H, C(6)H,
J = 12.7 Hz, J = 11.7 Hz, J = 3.5 Hz); 5.04 (d, 1 H, =CH, J = 1.2
Hz); 5.24 (d, 1 H, =CH, J = 1.2 Hz); 7.49 (s, 1 H, C(2)H); 7.57
(d, 2 H, Ph, J = 8.8 Hz); 8.00 (s, 1 H, C(2´)H); 8.33 (d, 2 H, Ph,
J = 8.8 Hz). 13C NMR, : 13.8, 24.1, 30.2, 39.7, 51.1, 52.3,
107.3, 110.2, 124.6 (2 C), 126.0, 128.0 (2 C), 142.0, 147.8 (2 C),
148.1, 152.1, 154.2, 165.2, 191.0. MS (DART MS), m/z: 425.1389
[M + H]+.
Dimethyl 1ꢀethylꢀ3´ꢀ(2ꢀmethoxyphenyl)ꢀ6´ꢀmethylideneꢀ4´ꢀ
oxoꢀ3´,4´,5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]ꢀ
pyrimidine]ꢀ2,3ꢀdicarboxylate (15i). The yield was 45 (the reacꢀ
tion in MeCN) and 50% (in MeOH), colorless crystals, m.p.
177—179 C, Rf 0.67 (Sorbfil, ethyl acetate). Found (%): C, 59.75;
H, 5.32; N, 8.55. C24H25N3O6S. Calculated (%): C, 59.61;
H, 5.21; N, 8.69. IR, /cm–1: 1737, 1685, 1678 (C=O). 1H NMR,
: 1.18 (t, 3 H, N—CH2CH3, J = 6.9 Hz); 1.88 (td, 1 H, C(5)H,
J = 13.1 Hz, J = 3.1 Hz); 2.30 (ddd, 1 H, C(5)H, J = 13.1 Hz,
J = 12.5 Hz, J = 4.3 Hz); 3.11—3.19 (m, 3 H, C(6)H, N—CH2Me);
3.48—3.54 (m, 4 H, C(6)H, CO2Me); 3.78 (s, 3 H, Ph—OCH3);
3.85 (s, 3 H, CO2Me); 5.22 (d, 1 H, =CH, J = 1.4 Hz); 5.31 (d, 1 H,
=CH, J = 1.4 Hz); 7.00—7.04 (m, 2 H, Ph); 7.21—7.26 (m, 1 H,
Ph); 7.40 (dt, 1 H, Ph, J = 8.3 Hz, J = 2.1 Hz); 7.88 (s, 1 H,
C(2´)H). 13C NMR, : 13.6, 29.9, 40.5, 47.9, 50.7, 52.6, 52.8,
55.9, 94.6, 108.5, 112.1, 120.8, 125.2, 125.7, 129.1, 130.8, 149.9,
150.9, 151.9, 154.4, 154.7, 136.8, 166.1, 166.3. MS, m/z (Irel (%)):
483 [M]+ (87), 452 (12), 425 (32), 424 (36), 423 (15), 393 (10),
392 (14), 379 (20), 369 (22), 367 (44), 366 (34), 364 (26), 349
(16), 335 (17), 310 (55), 309 (85), 308 (23), 295 (16), 279 (23),
251 (16), 241 (11), 207 (60), 203 (21), 276 (13), 260 (13), 147
(38), 133 (35), 120 (20), 107 (21), 92 (51), 91 (30), 77 (76),
70 (25), 59 (52), 57 (33), 44 (100).
Dimethyl 1ꢀethylꢀ6´ꢀmethylideneꢀ3´ꢀ(4ꢀnitrophenyl)ꢀ4´ꢀoxoꢀ
3´,4´,5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrꢀ
imidine]ꢀ2,3ꢀdicarboxylate (15f). The yield was 28 (the reaction
in MeCN) and 17% (in MeOH), light yellow crystals, m.p.
209—211 C. Rf 0.40 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 55.23; H, 4.53; N, 11.31. C23H22N4O7S. Calcuꢀ
lated (%): C, 55.41; H, 4.45; N, 11.24. IR, /cm–1: 1740, 1678
1
(C=O). H NMR, : 1.20 (t, 3 H, N—CH2CH3, J = 6.9 Hz);
1.90 (td, 1 H, C(5)H, J = 13.1 Hz, J = 3.4 Hz); 2.28 (ddd, 1 H,
C(5)H, J = 13.1 Hz, J = 12.3 Hz, J = 4.1 Hz); 3.15—3.23
(m, 3 H, C(6)H, N—CH2Me); 3.48—3.55 (m, 4 H, C(6)H,
CO2Me); 3.86 (s, 3 H, CO2CH3); 5.25 (d, 1 H, =CH, J = 2.0 Hz);
5.33 (d, 1 H, =CH, J = 2.0 Hz); 7.57 (d, 2 H, Ph, J = 8.9 Hz);
8.02 (s, 1 H, C(2´)H); 8.34 (d, 2 H, Ph, J = 8.9 Hz). 13C NMR,
: 13.6, 29.9, 40.6, 48.1, 51.0, 52.8, 94.5, 109.2, 124.7 (2 C),
125.6, 128.1 (2 C), 141.8, 147.7, 148.6, 148.7, 150.0, 151.3, 154.0,
165.0, 165.8, 166.0. MS (DART MS), m/z: 499.1277 [M + H]+.
Methyl 1ꢀethylꢀ6´ꢀmethylideneꢀ3´ꢀ(4ꢀnitrophenyl)ꢀ4´ꢀoxoꢀ
3´,4´,5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrꢀ
imidine]ꢀ3ꢀcarboxylate (15g). The yield was 25 (the reaction in
MeCN) and 51% (in MeOH), yellow crystals, m.p. 218—220 C,
Rf 0.47 (Sorbfil, ethyl acetate—hexane, 1 : 1). Found (%):
C, 57.17; H, 4.63; N, 12.81. C21H20N4O5S. Calculated (%):
C, 57.26; H, 4.58; N, 12.72. IR, /cm–1: 1668, 1614 (C=O).
1H NMR, : 1.22 (t, 3 H, N—CH2CH3, J = 7.1 Hz); 1.89 (td, 1 H,
C(5)H, J = 13.1 Hz, J = 3.5 Hz); 2.28 (ddd, 1 H, C(5)H,
J = 13.1 Hz, J = 11.9 Hz, J = 4.5 Hz); 3.10 (dt, 1 H, C(6)H,
J = 12.4 Hz, J = 4.5 Hz); 3.22—3.32 (m, 2 H, N—CH2Me); 3.42
(ddd, 1 H, C(6)H, J = 12.4 Hz, J = 11.9 Hz, J = 3.5 Hz); 3.58
(s, 3 H, CO2Me); 5.18 (d, 1 H, =CH, J = 1.3 Hz); 5.32 (d, 1 H,
=CH, J = 1.3 Hz); 7.59 (d, 2 H, Ph, J = 9.0 Hz); 7.67 (s, 1 H,
C(2)H); 8.03 (s, 1 H, C(2´)H); 8.34 (d, 2 H, Ph, J = 9.0 Hz).
13C NMR, : 13.9, 30.4, 39.6, 50.5, 50.8, 52.6, 95.9, 108.5, 124.7
(2 C), 125.6, 128.1 (2 C), 142.0, 146.4, 147.8, 148.6, 152.2,
154.5, 165.4, 166.7. MS (DART MS), m/z: 441.1225 [M + H]+.
Methyl 1ꢀethylꢀ3´ꢀ(2ꢀmethoxyphenyl)ꢀ6´ꢀmethylideneꢀ4´ꢀ
oxoꢀ3´,4´,5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]ꢀ
pyrimidine]ꢀ3ꢀcarboxylate (15j). The yield was 30 (the reaction
in MeCN) and 8% (in MeOH), light yellow crystals, m.p.
167—169 C, Rf 0.28 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 62.17; H, 5.49; N, 9.84. C22H23N3O4S. Calculatꢀ
ed (%): C, 62.10; H, 5.45; N, 9.88. IR, /cm–1: 1672, 1611
1
(C=O). H NMR, : 1.19 (t, 3 H, N—CH2CH3, J = 7.2 Hz);
1.87 (td, 1 H, C(5)H, J = 13.1 Hz, J = 3.4 Hz); 2.32 (ddd, 1 H,
C(5)H, J = 13.1 Hz, J = 11.8 Hz, J = 4.8 Hz); 3.05—3.09 (m, 1 H,
C(6)H); 3.23 (q, 2 H, N—CH2Me, J = 7.2 Hz); 3.39 (ddd, 1 H,
C(6)H, J = 12.5 Hz, J = 11.8 Hz, J = 3.4 Hz); 3.56 (s, 3 H,
CO2Me); 3.79 (s, 3 H, Ph—OCH3); 5.15 (d, 1 H, =CH, J = 1.4 Hz);
5.28 (d, 1 H, =CH, J = 1.4 Hz); 7.00—7.03 (m, 2 H, Ph);
7.24—7.26 (m, 1 H, Ph); 7.39 (td, 1 H, Ph, J = 8.2 Hz,
J = 2.0 Hz); 7.63 (s, 1 H, C(2)H); 7.90 (s, 1 H, C(2´)H). 13C
NMR, : 13.8, 30.6, 39.5, 50.3, 50.5, 52.4, 55.8, 96.2, 107.6,
112.0, 120.7, 125.4, 128.8, 129.3, 130.7, 146.3, 150.9, 152.8,
154.2, 155.1, 164.3, 166.8. MS, m/z (Irel (%)): 425 [M]+ (61),
392 (10), 378 (10), 368 (10), 367 (24), 366 (100), 352 (88), 324
(10), 309 (11), 207 (10), 92 (35), 91 (15), 77 (28), 44 (15).

Transformations of pyridothienopyrimidinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
377
3ꢀAcetylꢀ1ꢀethylꢀ3´ꢀ(2ꢀmethoxyphenyl)ꢀ6´ꢀmethylideneꢀ5,6ꢀ
dihydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrimidin]ꢀ4´(3´H)ꢀ
one (15k). Yield 46%, light yellow crystals, m.p. 194—196 C,
Rf 0.48 (Sorbfil, ethyl acetate). Found (%): C, 64.65; H, 5.58;
N, 10.27. C22H23N3O3S. Calculated (%): C, 64.53; H, 5.66;
52.5, 123.2, 128.5 (2 C), 129.8 (2 C), 131.3, 135.1, 135.4, 135.5,
144.9, 154.1, 157.7, 161.8, 167.1, 168.4, 168.8. MS (DART MS),
m/z: 488.05 [M + H]+.
Methyl 3ꢀ(4ꢀchlorophenyl)ꢀ7ꢀethylꢀ4ꢀoxoꢀ3,4,5,6,7,10ꢀhexaꢀ
hydropyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocineꢀ9ꢀcarboxylate
(16d). Yield 11% (the reaction in MeOH), white crystals, m.p.
275—278 C, Rf 0.57 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 58.39; H, 4.82; N, 9.68. C21H20ClN3O3S. Calcuꢀ
lated (%): C, 58.67; H, 4.69; N, 9.77. IR, /cm–1: 1688, 1665,
1617 (C=O). 1H NMR, : 1.19 (t, 3 H, N—CH2CH3, J = 7.3 Hz);
3.22 (q, 2 H, N—CH2Me, J = 7.3 Hz); 3.64 (t, 2 H, C(5)H2,
J = 5.8 Hz); 3.70 (s, 3 H, CO2Me); 3.89—3.94 (m, 2 H, C(6)H2);
4.10 (s, 2 H, C(10)H2); 7.32 (d, 2 H, Ph, J = 8.6 Hz); 7.48 (s, 1 H,
C(8)H); 7.50 (d, 2 H, Ph, J = 8.6 Hz); 7.93 (s, 1 H, C(2)H).
13C NMR, : 14.9, 24.6, 31.8, 45.7, 51.2, 51.9, 93.7, 124.0,
128.6 (2 C), 129.7 (2 C), 129.9, 135.3, 135.6, 136.8, 144.9,
149.9, 157.8, 161.1, 169.7. MS (DART MS), m/z: 430.0997
[M + H]+.
1
N, 10.26. IR, /cm–1: 1666 (C=O). H NMR, : 1.22 (t, 3 H,
N—CH2CH3, J = 7.3 Hz); 1.86 (td, 1 H, C(5)H, J = 13.4 Hz,
J = 3.4 Hz); 2.09 (s, 3 H, COMe); 2.29 (ddd, 1 H, C(5)H,
J = 13.4 Hz, J = 11.9 Hz, J = 4.2 Hz); 3.12 (dt, 1 H, C(6)H,
J = 12.9 Hz, J = 4.2 Hz); 3.28 (q, 2 H, N—CH2Me, J = 7.3 Hz);
3.42 (ddd, 1 H, C(6)H, J = 12.9 Hz, J = 11.9 Hz, J = 3.4 Hz);
3.78 (s, 3 H, Ph—OCH3); 5.02 (d, 1 H, =CH, J = 1.3 Hz); 5.20
(d, 1 H, =CH, J = 1.3 Hz); 6.98—7.02 (m, 2 H, Ph); 7.24—7.28
(m, 1 H, Ph); 7.38 (td, 1 H, Ph, J = 8.1 Hz, J = 1.5 Hz); 7.46
(br.s, 1 H, C(2)H); 7.87 (br.s, 1 H, C(2´)H). 13C NMR, : 13.9,
24.4, 29.8, 30.8, 39.9, 51.0, 52.3, 55.9, 106.4, 112.1, 120.9, 125.5,
125.8, 129.2, 130.8, 147.7, 150.6, 152.9, 154.4, 155.1, 164.5,
191.1. MS (DART MS), m/z: 410.1528 [M + H]+.
Dimethyl 1ꢀisopropylꢀ6´ꢀmethylideneꢀ4´ꢀoxoꢀ3´ꢀphenylꢀ
3´,4´,5,6ꢀtetrahydroꢀ1Hꢀspiro[pyridineꢀ4,5´ꢀthieno[2,3ꢀd]pyrꢀ
imidine]ꢀ2,3ꢀdicarboxylate (15l). Yield 57%, colorless crystals,
m.p. 139—140 C, Rf 0.60 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 61.46; H, 5.48; N, 9.09. C24H25N3O5S. Calculatꢀ
ed (%): C, 61.65; H, 5.39; N, 8.99. IR, /cm–1: 1734, 1679
9ꢀAcetylꢀ3ꢀ(4ꢀchlorophenyl)ꢀ7ꢀethylꢀ5,6,7,10ꢀtetrahydroꢀ
pyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocinꢀ4(3H)ꢀone (16e). Yield
7%, white crystals, m.p. 285—287 C, Rf 0.78 (Sorbfil, ethyl acetꢀ
ate). Found (%): C, 61.07; H, 4.92; N, 10.23. C21H20ClN3O2S.
Calculated (%): C, 60.94; H, 4.87; N, 10.15. IR, /cm–1: 1690,
1609 (C=O). 1H NMR, : 1.24 (t, 3 H, N—CH2CH3, J = 7.2 Hz);
2.21 (s, 3 H, COMe); 3.28 (q, 2 H, N—CH2Me, J = 7.2 Hz);
3.66 (t, 2 H, C(5)H2, J = 5.8 Hz); 3.94—4.00 (m, 2 H, C(6)H2);
4.19 (s, 2 H, C(10)H2); 7.30—7.32 (m, 3 H, Ph, C(8)H); 7.50
(d, 2 H, Ph, J = 8.7 Hz); 7.92 (s, 1 H, C(2)H). 13C NMR, : 14.9,
22.5, 24.7, 31.5, 45.9, 52.2, 108.3, 123.8, 128.5 (2 C), 129.7
(2 C), 135.3, 135.6, 137.0, 144.9, 151.7, 157.8, 161.2, 182.0, 193.3.
MS (DART MS), m/z: 414.1026 [M + H]+.
Dimethyl 7ꢀethylꢀ3ꢀ(4ꢀnitrophenyl)ꢀ4ꢀoxoꢀ3,4,5,6,7,10ꢀhexaꢀ
hydropyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocineꢀ8,9ꢀdicarboxylate
(16f). The yield was 12 (the reaction in MeCN) and 14% (in
MeOH), yellow crystals, m.p. 208—210 C, Rf 0.55 (Sorbfil,
ethyl acetate—hexane, 1 : 1). Found (%): C, 55.65; H, 4.52;
N, 11.32. C23H22N4O7S. Calculated (%): C, 55.41; H, 4.45;
N, 11.24. IR, /cm–1: 1739, 1678 (C=O). 1H NMR, : 1.05 (t, 3 H,
N—CH2CH3, J = 7.2 Hz); 3.04 (q, 2 H, N—CH2Me, J = 7.2 Hz);
3.69 (t, 2 H, C(5)H2, J = 6.5 Hz); 3.71 (s, 3 H, CO2Me); 3.81
(s, 3 H, CO2Me); 3.89 (t, 2 H, C(6)H2, J = 6.5 Hz); 4.11 (s, 2 H,
C(10)H2); 7.62 (d, 2 H, Ph, J = 8.9 Hz); 7.97 (s, 1 H, C(2)H);
8.41 (d, 2 H, Ph, J = 8.9 Hz). 13C NMR, : 14.1, 26.7, 28.1, 46.1,
48.4, 51.9, 52.7, 123.1, 124.9 (2 C), 128.4 (2 C), 131.3, 135.6,
142.3, 143.9, 144.0, 147.8, 154.1, 157.2, 161.6, 167.1, 168.4. MS
(DART MS), m/z: 499.1293 [M + H]+.
Methyl 7ꢀethylꢀ3ꢀ(4ꢀnitrophenyl)ꢀ4ꢀoxoꢀ3,4,5,6,7,10ꢀhexaꢀ
hydropyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocineꢀ9ꢀcarboxylate
(16g). The yield was 9 (the reaction in MeCN) and 3% (in
MeOH), light yellow crystals, m.p. 219—221 C, Rf 0.58 (Sorbfil,
ethyl acetate—hexane, 1 : 1). Found (%): C, 57.48; H, 4.64;
N, 12.80. C21H20N4O5S. Calculated (%): C, 57.29; H, 4.58;
N, 12.72. IR, /cm–1: 1680, 1621 (C=O). 1H NMR, : 1.20 (t, 3 H,
N—CH2CH3, J = 7.2 Hz); 3.23 (q, 2 H, N—CH2Me, J = 7.2 Hz);
3.64 (t, 2 H, C(5)H2, J = 5.6 Hz); 3.70 (s, 3 H, CO2Me);
3.90—3.95 (m, 2 H, C(6)H2); 4.11 (s, 2 H, C(10)H2); 7.49 (s, 1 H,
C(8)H); 7.61 (d, 2 H, Ph, J = 8.8 Hz); 7.96 (s, 1 H, C(2)H); 8.41
(d, 2 H, Ph, J = 8.8 Hz). 13C NMR, : 15.0, 24.7, 32.0, 45.8,
51.3, 52.0, 93.8, 124.0, 124.9 (2 C), 128.4 (2 C), 130.2, 137.5,
142.6, 144.1, 147.9, 150.0, 157.4, 161.2, 169.8. MS (DART MS),
m/z: 441.1244 [M + H]+.
1
(C=O). H NMR, : 1.19 (d, 3 H, N—CHCH3, J = 6.4 Hz);
1.21 (d, 3 H, N—CHCH3, J = 6.4 Hz); 1.88 (td, 1 H, C(5)H,
J = 13.1 Hz, J = 3.3 Hz); 2.22 (ddd, 1 H, C(5)H, J = 13.1 Hz,
J = 10.9 Hz, J = 5.5 Hz); 3.23—3.32 (m, 2 H, C(6)H2); 3.51
(s, 3 H, CO2Me); 3.59—3.66 (m, 1 H, N—CHMe2); 3.85 (s, 3 H,
CO2Me); 5.23 (d, 1 H, =CH, J = 1.7 Hz); 5.30 (d, 1 H, =CH,
J = 1.7 Hz); 7.31 (d, 2 H, Ph, J = 8.1 Hz); 7.42—7.50 (m, 3 H,
Ph); 8.00 (s, 1 H, C(2´)H). 13C NMR, : 20.2, 20.4, 29.9, 33.7,
50.8, 52.2, 52.6, 94.8, 108.7, 125.6, 126.9 (2 C), 129.1, 129.4
(2 C), 136.7, 147.3, 149.7, 150.2, 152.0, 154.7, 164.2, 166.2, 166.3.
MS (DART MS), m/z: 468.1612 [M + H]+.
Dimethyl 7ꢀethylꢀ4ꢀoxoꢀ3ꢀphenylꢀ3,4,5,6,7,10ꢀhexahydroꢀ
pyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocineꢀ8,9ꢀdicarboxylate (16b).
Yield 6%, white crystals, m.p. 183—184 C, Rf 0.63 (Sorbfil,
ethyl acetate—hexane, 1 : 1). Found (%): C, 60.94; H, 5.26;
N, 9.38. C23H23N3O5S. Calculated (%): C, 60.91; H, 5.11;
N, 9.27. IR, /cm–1: 1727, 1677 (C=O). 1H NMR, : 1.04 (t, 3 H,
N—CH2CH3, J = 7.1 Hz); 3.03 (q, 2 H, N—CH2Me, J = 7.1 Hz);
3.69—3.73 (m, 5 H, C(5)H2, CO2Me); 3.79 (s, 3 H, CO2Me);
3.87 (t, 2 H, C(6)H2, J = 6.5 Hz); 4.10 (s, 2 H, C(10)H2); 7.37
(d, 2 H, Ph, J = 7.1 Hz); 7.46—7.55 (m, 3 H, Ph); 7.99 (s, 1 H,
C(2)H). 13C NMR, : 14.1, 26.8, 28.0, 46.0, 48.7, 51.7, 52.5,
123.3, 127.2 (2 C), 129.2, 129.6 (2 C), 131.3, 134.8, 137.1, 145.4,
154.2, 156.2, 157.9, 161.8, 167.2, 168.4. MS (DART MS), m/z:
454.12 [M + H]+.
Dimethyl 3ꢀ(4ꢀchlorophenyl)ꢀ7ꢀethylꢀ4ꢀoxoꢀ3,4,5,6,7,10ꢀ
hexahydropyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocineꢀ8,9ꢀdicarbꢀ
oxylate (16c). The yield was 14 (the reaction in MeCN) and 6%
(in MeOH), white crystals, m.p. 213—215 C, Rf 0.63 (Sorbfil,
ethyl acetate—hexane, 1 : 1). Found (%): C, 56.70; H, 4.57;
N, 8.57. C23H22ClN3O5S. Calculated (%): C, 56.61; H, 4.54;
N, 8.61. IR, /cm–1: 1740, 1675 (C=O). 1H NMR, : 1.04 (t, 3 H,
N—CH2CH3, J = 7.1 Hz); 3.04 (q, 2 H, N—CH2Me, J = 7.1 Hz);
3.68—3.71 (m, 5 H, C(5)H2, CO2Me); 3.80 (s, 3 H, CO2Me);
3.87 (t, 2 H, C(6)H2, J = 6.4 Hz); 4.10 (s, 2 H, C(10)H2); 7.33
(d, 2 H, Ph, J = 8.7 Hz); 7.51 (d, 2 H, Ph, J = 8.7 Hz); 7.95
(s, 1 H, C(2)H). 13C NMR, : 14.1, 26.8, 28.1, 46.1, 48.7, 51.8,

378
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Voskressensky et al.
Dimethyl 7ꢀethylꢀ3ꢀ(2ꢀmethoxyphenyl)ꢀ4ꢀoxoꢀ3,4,5,6,7,10ꢀ
Ph); 7.98 (s, 1 H, C(2)H). 13C NMR, : 21.0 (2 C), 26.5, 29.3,
44.5, 51.6, 52.5, 53.0, 123.0, 127.2 (2 C), 129.2, 129.5 (2 C),
129.7, 132.5, 134.8, 137.2, 145.3, 154.0, 157.9, 161.5, 167.5,
168.3. MS (DART MS), m/z: 468.1740 [M + H]+.
hexahydropyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocineꢀ8,9ꢀdicarbꢀ
oxylate (16i). Yield 18% (the reaction in MeCN), white crystals,
m.p. 187—189 C, Rf 0.40 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 59.63; H, 5.32; N, 8.67. C24H25N3O6S. Calculatꢀ
ed (%): C, 59.61; H, 5.21; N, 8.69. IR, /cm–1: 1736, 1678
Dimethyl (2E)ꢀ2ꢀ(4ꢀoxoꢀ3ꢀphenylꢀ3,5,6,8ꢀtetrahydropyridoꢀ
[4´,3´:4,5]thieno[2,3ꢀd]pyrimidinꢀ7(4H)ꢀyl)butꢀ2ꢀenedioate (17).
Yield 11%, white crystals, m.p. 196—198 C, Rf 0.77 (Sorbfil,
ethyl acetate—hexane, 1 : 1). Found (%): C, 59.12; H, 4.69;
N, 10.00. C21H19N3O5S. Calculated (%): C, 59.28; H, 4.50;
N, 9.88. IR, /cm–1: 1737, 1688 (C=O). 1H NMR, : 3.21
(tt, 2 H, C(5)H2, J = 5.7 Hz, J = 1.6 Hz); 3.51 (t, 2 H, C(6)H2,
J = 5.7 Hz); 3.66 (s, 3 H, CO2Me); 3.97 (s, 3 H, CO2Me); 4.40
(t, 2 H, C(8)H2, J = 1.6 Hz); 4.88 (s, 1 H, =CH—); 7.37—7.39
(m, 2 H, Ph); 7.50—7.54 (m, 3 H, Ph); 8.03 (s, 1 H, C(2)H).
13C NMR, : 25.5, 45.3, 46.1, 50.9, 53.1, 87.4, 127.0 (2 C),
128.7, 129.3, 129.6 (2 C), 129.7, 130.5, 136.7, 146.1, 153.9, 157.2,
162.9, 165.7, 167.6. MS (DART MS), m/z: 426.1090 [M + H]+.
Dimethyl (2E)ꢀ2ꢀ{[2ꢀ(6ꢀhydroxymethylꢀ4ꢀoxoꢀ3ꢀphenylꢀ3,4ꢀ
dihydrothieno[2,3ꢀd]pyrimidinꢀ5ꢀyl)ethyl](Nꢀmethyl)amino}butꢀ
2ꢀenedioate (18). Yield 1%, white crystals, m.p. 150—152 C,
Rf 0.48 (Sorbfil, ethyl acetate—hexane, 1 : 2). Found (%): C, 57.82;
H, 5.15; N, 9.16. C22H23N3O6S. Calculated (%): C, 57.76;
H, 5.07; N, 9.18. IR, /cm–1: 1736, 1693 (C=O). 1H NMR, : 1.52
(s, 1 H, OH); 2.88 (s, 3 H, N—Me); 3.27—3.31 (m, 2 H, C()H2);
3.39—3.43 (m, 2 H, C()H2); 3.64 (s, 3 H, CO2Me); 3.94 (s, 3 H,
CO2Me); 4.64 (s, 1 H, =CH—); 4.84 (s, 2 H, CH2OH); 7.38—7.40
(m, 2 H, Ph); 7.52—7.59 (m, 3 H, Ph); 8.06 (s, 1 H, C(2)H).
13C NMR, : 26.6, 37.6, 42.9, 45.3, 50.8, 53.2, 84.7, 126.0,
127.1 (2 C), 128.8, 129.0, 129.8 (2 C), 132.0, 133.8, 146.2, 146.8,
154.5, 166.2, 168.8, 169.0. MS (DART MS), m/z: 476.09
[M + H3O]+.
Dimethyl (2E)ꢀ2ꢀ({2ꢀ[3ꢀ(4ꢀchlorophenyl)ꢀ6ꢀmethoxymethylꢀ
4ꢀoxoꢀ3,4ꢀdihydrothieno[2,3ꢀd]pyrimidinꢀ5ꢀyl]ethyl}(ethyl)amino)ꢀ
butꢀ2ꢀenedioate (19a). Yield 7%, white crystals, m.p. 173—175 C,
Rf 0.69 (Sorbfil, ethyl acetate—hexane, 1 : 1). Found (%): C,
55.45; H, 5.12; N, 8.08. C24H26ClN3O6S. Calculated (%): C,
55.43; H, 5.04; N, 8.08. IR, /cm–1: 1725, 1696, 1675 (C=O).
1H NMR, : 1.12 (t, 3 H, N—CH2CH3, J = 6.9 Hz); 3.17—3.25
(m, 4 H, N—CH2Me, C()H2); 3.35 (t, 2 H, C()H2, J = 6.7 Hz);
3.48 (s, 3 H, CH2OCH3); 3.64 (s, 3 H, CO2Me); 3.92 (s, 3 H,
CO2Me); 4.64 (s, 2 H, CH2OMe); 4.72 (br.s, 1 H, =CH—); 7.35
(d, 2 H, Ph, J = 8.7 Hz); 7.53 (d, 2 H, Ph, J = 8.7 Hz); 7.90
(s, 1 H, C(2)H). 13C NMR, : 12.0, 26.6, 36.1, 47.6, 50.7, 52.9,
58.6, 66.7, 83.4, 122.8, 128.5 (2 C), 129.9 (2 C), 132.1, 135.4,
135.5, 136.1, 145.7, 153.7, 157.4, 163.5, 166.2, 168.3. MS (DART
MS), m/z: 520.1234 [M + H]+.
1
(C=O). H NMR, : 1.03 (t, 3 H, N—CH2CH3, J = 7.3 Hz);
3.04 (q, 2 H, N—CH2Me, J = 7.3 Hz); 3.70—3.72 (m, 5 H,
C(5)H2, CO2Me); 3.80 (s, 6 H, CO2Me, Ph—OCH3); 3.87 (t, 2 H,
C(6)H2, J = 6.3 Hz); 4.09 (s, 2 H, C(10)H2); 7.06—7.10 (m, 2 H,
Ph); 7.29 (dd, 1 H, Ph, J = 8.1 Hz, J = 1.9 Hz); 7.46 (dt, 1 H,
Ph, J = 8.1 Hz, J = 1.9 Hz); 7.85 (s, 1 H, C(2)H). 13C NMR, :
14.1, 26.7, 28.0, 46.0, 48.8, 51.7, 52.5, 55.8, 97.2, 112.2, 120.9,
123.5, 125.6, 129.1, 131.0, 131.2, 134.1, 146.5, 151.2, 151.6,
157.9, 161.8, 167.2, 168.5. MS, m/z (Irel (%)): 483 [M]+ (10),
412 (10), 380 (11), 349 (10), 335 (24), 309 (97), 308 (42), 291
(19), 279 (19), 278 (100), 277 (21), 251 (10), 211 (10), 208 (10),
207 (45), 205 (10), 203 (41), 191 (10), 186 (11), 147 (17), 133
(20), 120 (16), 105 (15), 97 (19), 92 (31), 77 (50), 70 (24), 63
(37), 55 (36), 53 (28), 44 (79), 43 (42).
Methyl 7ꢀethylꢀ3ꢀ(2ꢀmethoxyphenyl)ꢀ4ꢀoxoꢀ3,4,5,6,7,10ꢀ
hexahydropyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocineꢀ9ꢀcarboxylꢀ
ate (16j). Yield 12% (the reaction in MeCN), white crystals,
m.p. 195—197 C, Rf 0.61 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 62.12; H, 5.52; N, 9,87. C22H23N3O4S. Calculatꢀ
ed (%): C, 62.10; H, 5.45; N, 9.88. IR, /cm–1: 1678, 1658, 1612
1
(C=O). H NMR, : 1.19 (t, 3 H, N—CH2CH3, J = 7.2 Hz);
3.22 (q, 2 H, N—CH2Me, J = 7.2 Hz); 3.64—3.66 (m, 2 H,
C(5)H2); 3.69 (s, 3 H, Ph—OCH3); 3.80 (s, 3 H, CO2Me);
3.90—3.93 (m, 2 H, C(6)H2); 4.09 (s, 2 H, C(10)H2); 7.05—7.09
(m, 2 H, Ph); 7.28 (dd, 1 H, Ph, J = 8.1 Hz, J = 1.9 Hz); 7.45
(dt, 1 H, Ph, J = 8.1 Hz, J = 1.9 Hz); 7.49 (s, 1 H, C(8)H); 7.83
(s, 1 H, C(2)H). 13C NMR, : 14.8, 24.5, 31.8, 45.7, 51.2, 51.8,
55.8, 93.7, 112.1, 120.8, 124.3, 125.6, 129.2, 129.9, 130.9, 135.8,
146.5, 149.9, 154.6, 157.9, 161.1, 169.7. MS (DART MS), m/z:
426.1546 [M + H]+.
9ꢀAcetylꢀ7ꢀethylꢀ3ꢀ(2ꢀmethoxyphenyl)ꢀ5,6,7,10ꢀtetrahydroꢀ
pyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocinꢀ4(3H)ꢀone (16k). Yield
10%, white crystals, m.p. 211—213 C, Rf 0.47 (Sorbfil, ethyl
acetate—hexane, 1 : 1). Found (%): C, 64.69; H, 5.78; N, 10.14.
C22H23N3O3S. Calculated (%): C, 64.53; H, 5.66; N, 10.26. IR,
1
/cm–1: 1675 (C=O). H NMR, : 1.23 (t, 3 H, N—CH2CH3,
J = 7.2 Hz); 2.21 (s, 3 H, COMe); 3.28 (q, 2 H, N—CH2Me,
J = 7.2 Hz); 3.66—3.70 (m, 2 H, C(5)H2); 3.80 (s, 3 H, Ph—OCH3);
3.92—3.99 (m, 2 H, C(6)H2); 4.09 (br.s, 2 H, C(10)H2); 7.06—7.09
(m, 2 H, Ph); 7.28 (dd, 1 H, Ph, J = 7.7 Hz, J = 1.4 Hz); 7.32
(s, 1 H, C(8)H); 7.46 (dt, 1 H, Ph, J = 7.7 Hz, J = 1.4 Hz); 7.82
(s, 1 H, C(2)H). 13C NMR, : 14.9, 22.6, 24.8, 31.6, 46.1, 52.3,
55.9, 108.5, 112.3, 121.0, 124.3, 125.7, 129.3, 129.9, 131.0, 136.2,
146.6, 151.9, 154.8, 158.0, 161.4, 193.4. MS (DART MS), m/z:
410.1531 [M + H]+.
Dimethyl 7ꢀisopropylꢀ4ꢀoxoꢀ3ꢀphenylꢀ3,4,5,6,7,10ꢀhexaꢀ
hydropyrimido[5´,4´:4,5]thieno[3,2ꢀd]azocineꢀ8,9ꢀdicarboxylate
(16l). Yield 11%, white crystals, m.p. 177—178 C, Rf 0.68 (Sorbfil,
ethyl acetate—hexane, 1 : 1). Found (%): C, 61.57; H, 5.53;
N, 8.78. C24H25N3O5S. Calculated (%): C, 61.65; H, 5.39;
N, 8.99. IR, /cm–1: 1736, 1678 (C=O). 1H NMR, : 1.13 (d, 6 H,
N—CH(CH3)2, J = 6.6 Hz); 3.47 (sept, 1 H, N—CHMe2,
J = 6.6 Hz); 3.67—3.70 (m, 5 H, C(5)H2, CO2Me); 3.81 (s, 3 H,
CO2Me); 3.83 (t, 2 H, C(6)H2, J = 6.2 Hz); 4.03 (s, 2 H,
C(10)H2); 7.36 (d, 2 H, Ph, J = 7.4 Hz); 7.48—7.55 (m, 3 H,
Dimethyl (2E)ꢀ2ꢀ(ethyl{2ꢀ[6ꢀmethoxymethylꢀ3ꢀ(2ꢀmethoxꢀ
yphenyl)ꢀ4ꢀoxoꢀ3,4ꢀdihydrothieno[2,3ꢀd]pyrimidinꢀ5ꢀyl]ethyl}ꢀ
amino)butꢀ2ꢀenedioate (19b). Yield 12%, white crystals, m.p.
147—149 C, Rf 0.55 (Sorbfil, ethyl acetate—hexane, 1 : 1).
Found (%): C, 58.31; H, 5.72; N, 8.14. C25H29N3O7S. Calculatꢀ
ed (%): C, 58.24; H, 5.67; N, 8.15. IR, /cm–1: 1732, 1692, 1671
1
(C=O). H NMR, : 1.09 (t, 3 H, N—CH2CH3, J = 6.8 Hz);
3.14—3.19 (m, 2 H, N—CH2Me); 3.23 (t, 2 H, C()H2, J = 7.2 Hz);
3.35—3.39 (m, 2 H, C()H2); 3.48 (s, 3 H, CH2OCH3); 3.63
(s, 3 H, CO2Me); 3.82 (s, 3 H, Ph—OCH3); 3.91 (s, 3 H, CO2Me);
4.63 (s, 2 H, CH2OMe); 4.71 (br.s, 1 H, =CH—); 7.08—7.12
(m, 2 H, Ph); 7.31 (dd, 1 H, Ph, J = 8.2 Hz, J = 1.4 Hz); 7.49
(dt, 1 H, Ph, J = 8.2 Hz, J = 1.4 Hz); 7.90 (s, 1 H, C(2)H).
13C NMR, : 15.2, 25.6, 36.1, 47.6, 50.7, 52.8, 55.8, 58.5, 66.7,
83.2, 112.4, 121.0, 123.0, 125.5, 129.1, 131.1, 132.2, 135.2, 147.2,

Transformations of pyridothienopyrimidinones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 2, February, 2012
379
153.8, 154.6, 157.4, 163.5, 166.1, 168.3. MS (DART MS), m/z:
516.1796 [M + H]+.
Ser. Khim., 2005, 2513 [Russ. Chem. Bull., Int. Ed., 2005,
54, 2594].
Methyl (2E)ꢀ3ꢀ(ethyl{2ꢀ[6ꢀmethoxymethylꢀ3ꢀ(2ꢀmethoxyꢀ
phenyl)ꢀ4ꢀoxoꢀ3,4ꢀdihydrothieno[2,3ꢀd]pyrimidinꢀ5ꢀyl]ethyl}ꢀ
amino)acrylate (19c). Yield 44%, white crystals, m.p. 126—128 C,
Rf 0.67 (Sorbfil, ethyl acetate—hexane, 1 : 1). Found (%):
C, 60.42; H, 6.02; N, 9.17. C23H27N3O5S. Calculated (%):
C, 60.38; H, 5.95; N, 9.18. IR, /cm–1: 1679 (C=O). 1H NMR,
: 1.08 (t, 3 H, N—CH2CH3, J = 6.9 Hz); 3.13 (q, 2 H,
N—CH2Me, J = 6.9 Hz); 3.20 (t, 2 H, C()H2, J = 6.3 Hz); 3.40
(t, 2 H, C()H2, J = 6.3 Hz); 3.46 (s, 3 H, CH2OCH3); 3.65
(s, 3 H, Ph—OCH3); 3.82 (s, 3 H, CO2Me); 4.57—4.70 (m, 3 H,
CH2OMe, CH=CH—CO2Me); 7.05—7.13 (m, 2 H, Ph); 7.33
(dd, 1 H, Ph, J = 7.8 Hz, J = 1.4 Hz); 7.41—7.49 (m, 2 H, Ph,
CH=CH—CO2Me); 7.90 (s, 1 H, C(2)H). 13C NMR, : 14.5,
24.5, 43.1, 50.4, 55.5, 55.8, 58.5, 66.8, 83.4, 112.3, 121.0, 123.1,
125.5, 129.1, 131.1, 132.9, 134.6, 147.3, 151.1, 154.6, 157.4,
163.5, 170.2. MS (DART MS), m/z: 458.1754 [M + H]+.
2. L. G. Voskressensky, A. V. Listratova, T. N. Borisova, S. A.
Kovaleva, R. S. Borisov, A. V. Varlamov, Tetrahedron, 2008,
64, 10443.
3. L. G. Voskressensky, T. N. Borisova, L. N. Kulikova, A. V.
Varlamov, M. Catto, C. Altomare, A. Carotti, Eur. J. Org.
Chem., 2004, 3128.
4. L. G. Voskressensky, T. N. Borisova, I. S. Kostenev, L. N.
Kulikova, A. V. Varlamov, Tetrahedron Lett., 2006, 47, 999.
5. L. G. Voskressensky, A. V. Listratova, T. N. Borisova, G. G.
Alexandrov, A. V. Varlamov, Eur. J. Org. Chem., 2007, 6106.
6. L. G. Voskressensky, S. A. Kovaleva, T. N. Borisova, A. V.
Listratova, V. S. Tolkunov, A. B. Eresko, S. V. Tolkunov,
A. V. Varlamov, Khim. Geterotsikl. Soedin., 2010, 449 [Chem.
Heterocycl. Compd. (Engl. Transl.), 2010, 46, 356].
7. L. G. Voskressensky, S. A. Kovaleva, T. N. Borisova, A. V.
Listratova, A. B. Eresko, V. S. Tolkunov, S. V. Tolkunov,
A. V. Varlamov, Tetrahedron, 2010, 66, 9421.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 11ꢀ03ꢀ00164).
8. L. G. Voskressensky, A. V. Listratova, T. N. Borisova, S. A.
Kovaleva, R. S. Borisov, A. V. Varlamov, Tetrahedron, 2008,
64, 10443.
9. G. M. Sheldrick, Acta Crystallogr., 2008, A64, 112.
References
1. L. G. Voskressensky, T. N. Borisova, T. A. Vorob´eva,
A. I. Chernyshev, A. V. Varlamov, Izv. Akad. Nauk,
Received June 15, 2011;
in revised form December 28, 2011