Thieno[2,3-d]pyrimidin-4-ones 1. condensation of 2,3-dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydro-pyrrolo[1,2-a]thieno[2, 3-d]pyriminidin-4(6H)-ones with aromatic aldehydes and furfural

Article abstract of DOI:10.1007/s10593-011-0677-4

2,3-Dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-substituted 8-arylidene-6,7-dihydro-pyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4-ones were synthesized by the reaction of 2,3-dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydropy

Full text of DOI:10.1007/s10593-011-0677-4

Chemistry of Heterocyclic Compounds, Vol. 46, No. 11, February, 2011 (Russian Original Vol. 46, No. 11, November, 2010)
THIENO[2,3-d]PYRIMIDIN-4-ONES
1. CONDENSATION OF 2,3-DIMETHYL- AND 2,3-TRI-,
2,3-TETRA-, AND 2,3-PENTAMETHYLENE-7,8-DIHYDRO-
PYRROLO[1,2-a]THIENO[2,3-d]PYRIMINIDIN-4(6H)-ONES
WITH AROMATIC ALDEHYDES AND FURFURAL
B. Zh. Elmuradov1*, Kh. A. Bozorov1, and Kh. M. Shakhidoyatov1
2,3-Dimethyl- and 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-substituted 8-arylidene-6,7-dihydro-
pyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4-ones were synthesized by the reaction of 2,3-dimethyl- and
2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-
ones with benzaldehyde, its 4-dimethylamino-, 3,4-dimethoxy-, and 3,4-methylenedioxy derivatives and
also furfural in the presence of NaOH.
Keywords: arylidene derivatives, aromatic aldehydes, thieno[2,3-d]pyrimidin-4-ones, furfural,
condensation.
Among the large number of compounds of the thieno[2,3-d]pyrimidin-4-one series annelated at both
heterocycles, derivatives of type I have been little studied. At the same time, among them are known substances
which possess various biological activities (fungicidal, bactericidal, anti-inflammatory, etc.) [3-9], which shows
potential for further synthesis and the study of properties of substances with similar structures.
The objective of the present work is the synthesis of new derivatives of type I. They are traditionally
synthesized from 2-amino-3-ethoxycarbonyl-4,5-disubstituted thiophenes by condensation with lactams [10, 11]
or O-alkyl esters of lactams [3], and also from cyclic ketones by the Gewald reaction [12,13]. Oxidation [14, 15]
and formylation [16, 17] of such compounds occurs exclusively at the CH2 group of ring A connected with the
heterocyclic system of rings B and C at position 2.
O
N
(CH2)m
n(H C)
A
D
B
S
C
N
2
I
_______
* To whom correspondence should be addressed, e-mail: belmuradov@yahoo.com.
1S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences, Republic of Uzbekistan,
Tashkent 100170, Uzbekistan.
__________________________________________________________________________________________
Translated from Khimiya Geterotisklicheskikh Soedinenii, No. 11, 1717-1724, November, 2010.
Original article submitted November 19, 2009, revised version submitted May 25, 2010.
0009-3122/11/4611-1393©2011 Springer Science+Business Media, Inc.
1393

It is also known that tricyclic quinazoline alkaloids – 2,3-tri- and 2,3-tetramethylene-3,4-dihydro-
quinazolin-4-ones and their substituents and homologs – condense with aromatic and heterocyclic aldehydes at
the CH2 group connected to the quinazolinone nucleus, similar to the 6-CH2 group of type I compounds, and
form in this way either arylidene- or arylhydroxymethylderivatives [18, 22]. There are no in the data literature
on the interactions of tri(tetra)cyclic 7,8-dihydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-ones, thiophene
analogs of the alkaloids mentioned.
We have obtained the known 2,3-dimethyl-, 2,3-tri-, 2,3-tetra-, and 2,3-pentamethylene-7,8-dihydro-
pyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-ones 5-8 from 4,5-dimethyl- and 4,5-tri-, 4,5-tetra-, and 4,5-penta-
methylene-substituted 2-amino-3-ethoxycarbonylthiophenes 1-4 and γ-butyrolactam in the presence of
phosphorus oxychloride, and we have studied the reactions of compounds 5-8 with benzaldehyde (9a), 4-di-
methylamino- (9b), 3,4-dimethoxy- (9c), 3,4-methylenebisoxybenzaldehyde (9d) and also furfural (9e):
O
R
6
8
COOEt
NH2
R
5
3
HN
POCl3
N
4
7
+

R1
O
R1
S
S
1
N
2
9
1–4
5–8
1, 5 R = R1 = Me, 2, 6 R + R1 = (CH2)3, 3, 7 R + R1 = (CH2)4, 4, 8 R + R1 = (CH2)5
The synthesis of compounds 5-8 was carried out by a modified methodology [11]. Addition of POCl3 to
the reagents on cooling, rather than at room temperature, an increased reaction time and treatment of the reaction
mixture with ice water gave products 5-8 in high yields (82-96%).
1
The structures of the compounds synthesized were confirmed from the H NMR spectra cited in the
Experimental section, which agree with known data for structurally related compounds [10, 20-22]. The
characteristics which are important for further analysis of the direction of the interaction of compounds 5-8 with
the aldehydes 9 are the signals of protons H-6 and H-8 each appearing as two-proton triplets in the regions 4.10-
4.11 (J = 7.1-7.3) and 3.07-3.10 ppm (J = 7.9-8.1 Hz) respectively.
As a result of the condensation of dihydrothienopyrrolopyrimidin-4-ones 5-8 with aldehydes 9a-e under
optimal conditions (boiling the reagents for 7-8 h in ethanol in the presence of NaOH in the ratio of 5-8:9:NaOH
equal to 1:1:0.3) the corresponding 8-arylidenhetarylidene-substituted compounds 10a-e – 13a-e were obtained
in 61-96% yields. The highest yields were obtained in the case of furfural (89-96%). We have previously
reported the synthesis of compounds 10, 11 (see [23, 24]).
O
R
N
Ar(Het)CHO
5–8
+
R1
S
N
9a–e
HC
Ar(Het)
10–13 a–e
5, 10a–e R = R1 = Me; 6, 11a–e R + R1 = (CH2)3; 7, 12a–e R + R1 = (CH2)4;
8, 13a–e R + R1 = (CH2)5; 9a–d – 13a–d Ar = C6H3 R2-m, R3-p, a R2 = R3 = H, b R2 = H,
R3 = N(Me)2, c R2 = R3 = OMe, d R2 + R3 = OCH2O; 9e–13e Het = furyl-2
To elucidate the influence of various factors on the interaction of aldehydes 9 with compounds 6-8 (for
example, it was expected that it would also occur at position 2-CH2 of the latter), we have carried out condensation
of the aldehydes 9b-e with compound 6 with various ratios of the reagents (9b-e:6 = 2:1, 3:1, 4:1) under different
conditions: in ethanol with NaOH at room temperature (2-24 h duration), and at 80°C (2-8 h), and in boiling glacial
1394

acetic acid (2-4 h). However, only formation of products 11b-e was observed in all cases. The highest yields were
achieved under the optimal conditions noted above for the synthesis of compounds 10-13.
The composition and structure of the synthesized compounds 10a-e – 13a-e were confirmed by the
results of elemental analyses (Table 1) and by IR and 1H NMR spectral data (Tables 2 and 3).
The IR spectra of these compounds contained absorption bands for the C=O, C=N, and C–N groups in the
regions of 1651-1670, 1531-1596, and 1466-1514 cm-1 respectively, being in agreement with literature data [10,
12].
1
The basic differences between the H NMR spectra of the products 10a-e – 13a-e and those of the
starting materials 5-8 are the absence of signals for the H-8 protons and the presence of signals of the
=CHAr(Het) group. In addition, the multiplicity of the signals of H-7 proton takes the form of a triplet of
doublets with a coupling constant (J = 2.4-2.7 Hz) to the protons of the =CHAr(Het) group, as noted previously
TABLE 1. Characteristics of the Compounds Synthesized
Com-
pound
Empirical
formula
Found N, %
Calculated N, %
mp, °C
——————
Rf *
Yield, %
69
(benzene)
10a
C18H16N2OS
8.91
9.09
0.87
225-227
10b
10c
10d
10e
11a
11b
11c
11d
11e
12a
12b
12c
12d
12e
13a
13b
13c
13d
13e
C20H21N3OS
C20H20N2O3S
C19H16N2O3S
C16H14N2O2S
C19H16N2OS
C21H21N3OS
C21H20N2O3S
C20H16N2O3S
C17H14N2O2S
C20H18N2OS
C22H23N3OS
C22H22N2O3S
C21H18N2O3S
C18H16N2O2S
C21H20N2OS
C23H25N3OS
C23H24N2O3S
C22H20N2O3S
C19H18N2O2S
11.87
11.96
7.51
7.60
8.04
7.95
9.50
9.39
8.66
8.75
11.69
11.57
7.45
7.36
7.54
7.69
8.90
9.03
8.23
8.38
11.22
11.14
6.98
7.13
7.23
7.40
8.80
8.64
7.90
8.04
10.59
10.74
0.75
0.59
0.81
0.67
0.81
0.84
0.68
0.83
0.83
0.87
0.79
0.80
0.89
0.77
0.87
0.90
0.86
0.83
0.88
260-261
249-250
233-235
264
65
64
68
89
72
71
64
65
93
79
68
72
66
96
61
71
78
84
90
250
274-275
242-244
260-262
242*2
238-240
264-266
253-255
278-280
236-238
233-235
263-265
230-231
254-255
241-242
6.99
6.86
7.01
7.14
8.09
8.28
_______
* Systems for TLC: benzene–methanol 5:1 (compounds 10a-e, 11a,c,d, 12a-e,
13a-e), benzene–methanol 3:1 (compounds 11b,e).
*2 Compound 11e was recrystallized from a benzene–hexane 2:1 mixture.
1395

[10, 20-22, 25]. The spectra of compounds 10b,c are exceptional: the signals of H-7 protons are triplets, and the
methyne protons are broad singlets, as was noted [26] for 3-dimethylaminomethylidene-1,2,3,9-tetra-
hydropyrrolo[2,1-b]quinazolone-4. One should also note the shifts of the signals of H-6 and H-7 protons to weak
field by 0.1 in the first case and 1 ppm in the second case.
TABLE 2. IR Spectra of the Compounds Synthesized
Com-
pound
ν, cm–1
Com-
pound
ν, cm–1
C=O
C=N
CN
C=O
C=N
CN
10a
10b
10c
10d
10e
11a
11b
11c
11d
11e
1664
1651
1664
1668
1653
1656
1659
1668
1668
1663
1575
1538
1576
1551
1553
1572
1531
1577
1533
1542
1507
1467
1514
1503
1509
1490
1475
1466
1489
1474
12a
12b
12c
12d
12e
13a
13b
13c
13d
13e
1652
1652
1668
1661
1656
1670
1660
1662
1661
1661
1570
1570
1596
1546
1552
1582
1552
1579
1546
1554
1475
1475
1470
1488
1475
1470
1481
1466
1488
1471
TABLE 3. 1H NMR Spectra of the Compounds Synthesized
Com-
pound
Chemical shifts, ppm (J, Hz)*
1
10a
10b
2
2.33 (3H, s, 2-CH3); 2.43 (3H, s, 3-CH3); 3.24 (2H, td, J = 6.5, J = 2.8, Н-7);
4.19 (2Н, t, J = 6.5, Н-6); 7.29-7.47 (5Н, m, Н Ph); 7.64 (1Н, t, J = 2.8, CНPh)
2.09 (3H, s, 2-CH3); 2.11 (3H, s, 3-CH3); 3.06 (6H, s, N(CН3)2); 3.16 (2Н, t, J = 6.5, Н-7);
4.23 (2Н, t, J = 6.5, Н-6); 7.37 (2Н, d, J = 8.9, Н-3,5 Ar); 7.44 (2Н, d, J = 8.9, Н-2,6 Ar);
7.54 (1Н, br. s, CНAr)
10c
10d
2.07 (3H, s, 2-CH3); 2.09 (3H, s, 3-CH3); 3.16 (2H, t, J = 6.8, Н-7); 3.58 (6H, s, 2ОСН3);
4.19 (2Н, t, J = 6.8, Н-6); 6.72 (1Н, d, J = 8.6, Н-5 Ar); 6.80 (1Н, d, J = 2.0, Н-2 Ar);
6.95 (1Н, dd, J = 8.6, J = 2.0, Н-6 Ar); 7.43 (1Н, br. s, CНAr)
2.32 (3H, s, 2-CH3); 2.42 (3H, s, 3-CH3); 3.18 (2H, td, J = 6.7, J = 2.7, Н-7);
4.17 (2Н, t, J = 6.7, Н-6); 5.96 (2Н, s, ОСН2); 6.80 (1Н, d, J = 8.0, Н-5 Ar);
6.95 (1Н, d, J = 1.8, Н-2 Ar); 6.98 (1Н, dd, J = 8.0, J = 1.8, Н-6 Ar);
7.54 (1Н, t, J = 2.7, CНAr)
10e
11a
11b
11c
2.06 (3H, s, 2-CH3); 2.09 (3H, s, 3-CH3); 3.19 (2H, td, J = 7.2, J = 2.4, Н-7);
4.16 (2H, t, J = 7.2, Н-6); 6.28 (1Н, dd, J = 3.4, J = 1.7, Н-4 Het);
6.63 (1Н, d, J = 3.4, Н-3 Het); 7.27 (1Н, t, J = 2.4, CНHet); 7.38 (1Н, d, J = 1.7, Н-5 Het)
2.37-2.43 (2H, m, 2-СH2СH2); 2.90 (2H, t, J = 7.0, 2-СH2); 3.02 (2H, t, J = 7.0, 3-СН2);
3.25 (2Н, td, J = 7.2, J = 2.7, Н-7); 4.20 (2Н, t, J = 7.2, Н-6); 7.30-7.47 (5Н, m, Н Ph);
7.65 (1Н, t, J = 2.7, CНPh)
2.39-2.41 (2H, m, 2-СH2СH2); 2.90 (2H, t, J = 7.0, 2-СН2); 3.03 (6H, s, N(CН3)2);
3.10 (2Н, t, J = 7.0, 3-СН2); 3.23 (2Н, td, J = 7.2, J = 2.6, Н-7); 4.21 (2Н, t, J = 7.2, Н-6);
6.85 (2Н, d, J = 8.9, Н-3,5 Ar); 7.43 (2Н, d, J = 8.9, Н-2,6 Ar); 7.60 (1Н, t, J = 2.6, CНAr)
2.38-2.41 (2H, m, 2-СH2СH2); 2.89 (2H, t, J = 7.1, 2-СН2); 3.01 (2H, t, J = 7.3, 3-СН2);
3.23 (2H, td, J = 6.7, J = 2.8, Н-7); 3.86, 3.87 (3H, s and 3H, s, ОСН3);
4.21 (2Н, t, J = 6.7, Н-6); 6.87 (1Н, d, J = 8.3, Н-5 Ar); 6.98 (1Н, d, J = 2.0, Н-2 Ar);
7.08 (1Н, dd, J = 8.3, J = 2.0, Н-6 Ar); 7.60 (1Н, t, J = 2.8, CНAr)
11d
11e
2.38-2.41 (2H, m, 2-СH2СH2); 2.89 (2H, t, J = 6.9, 2-СН2); 3.02 (2H, t, J = 7.3, 3-СН2);
3.20 (2H, td, J = 7.1, J = 2.8, Н-7); 4.19 (2Н, t, J = 7.1, Н-6); 5.96 (2Н, s, ОСН2);
6.81 (1Н, d, J = 8.0, Н-5 Ar); 6.96 (1Н, d, J = 1.6, Н-2 Ar);
6.98 (1Н, dd, J = 8.0, J = 1.6, Н-6 Ar); 7.56 (1Н, t, J = 2.8, CНAr)
2.37-2.40 (2H, m, 2-СH2СH2); 2.90 (2H, t, J = 7.2, 2-СН2); 3.01 (2H, t, J = 7.3, 3-СН2);
3.27 (2H, td, J = 6.8, J = 2.7, Н-7); 4.18 (2H, t, J = 6.8, Н-6);
6.46 (1Н, dd, J = 3.4, J = 1.7, Н-4 Het); 6.52 (1Н, d, J = 3.4, Н-3 Het);
7.40 (1Н, t, J = 2.7, CНHet); 7.50 (1Н, d, J = 1.7, Н-5 Het)
1396

TABLE 3 (continued)
1
2
12a
12b
12c
1.76-1.84 (4H, m, 2-СH2(СH2)2); 2.72 (2H, t, J = 6.1, 2-СН2); 2.97 (2H, t, J = 6.1, 3-СН2);
3.24 (2Н, td, J = 6.6, J = 2.9, Н-7); 4.18 (2Н, t, J = 6.6, Н-6); 7.27-7.48 (5Н, m, H Ph);
7.64 (1Н, t, J = 2.9, CНPh)
1.76-1.83 (4H, m, 2-СH2(СH2)2); 2.70 (2H, t, J = 5.8, 2-СН2); 2.96 (6H, s, N(CН3)2);
2.98 (2H, t, J = 5.4, 3-СН2); 3.19 (2Н, td, J = 7.1, J = 2.6, Н-7); 4.15 (2Н, t, J = 7.1, Н-6);
6.66 (2Н, d, J = 9.0, Н-3,5 Ar); 7.38 (2Н, d, J = 9.0, Н-2,6 Ar); 7.56 (1Н, t, J = 2.6, CНAr)
1.78-1.82 (4H, m, 2-СH2(СH2)2); 2.71 (2H, t, J = 6.0, 2-СН2); 2.96 (2H, t, J = 6.0, 3-СН2);
3.22 (2H, td, J = 7.2, J = 2.7, Н-7); 3.86, 3.87 (3H, s and 3H, s, ОСН3);
4.18 (2Н, t, J = 7.2, Н-6); 6.87 (1Н, d, J = 8.4, Н-5 Ar); 7.0 (1Н, d, J = 1.9, Н-2 Ar);
7.08 (1Н, dd, J = 8.4, J = 1.9, Н-6 Ar); 7.58 (1Н, t, J = 2.7, CНAr)
12d
12e
13b
13c
1.77-1.82 (4H, m, 2-СH2(СH2)2); 2.71 (2H, t, J = 6.0, 2-СН2); 2.96 (2H, t, J = 6.0, 3-СН2);
3.19 (2H, td, J = 7.1, J = 2.8, Н-7); 4.17 (2Н, t, J = 7.1, Н-6); 5.96 (2Н, s, ОСН2);
6.81 (1Н, d, J = 8.0, Н-5 Ar); 6.95 (1Н, d, J = 1.4, Н-2 Ar);
6.98 (1Н, dd, J = 8.0, J = 1.4, Н-6 Ar); 7.55 (1Н, t, J = 2.8, CНAr)
1.77-1.82 (4H, m, 2-СH2(СH2)2); 2.70 (2H, t, J = 6.0, 2-СН2); 2.96 (2H, t, J = 6.0, 3-СН2);
3.26 (2H, td, J = 7.1, J = 2.8, Н-7); 4.16 (2H, t, J = 7.1, Н-6);
6.45 (1Н, dd, J = 3.4, J = 1.7, Н-4 Het); 6.51 (1Н, d, J = 3.4, Н-3 Het);
7.40 (1Н, t, J = 2.8, CНHet); 7.49 (1Н, d, J = 1.7, Н-5 Het)
1.62-1.66 (4H, m, 2-СH2(СH2)2); 1.81-1.83 (2H, m, 3-СH2СH2);
2.77 (2H, t, J = 5.8, 2-СН2); 2.97 (6H, s, N(CН3)2); 3.20 (2H, td, J = 6.6, J = 2.6, Н-7);
3.29 (2Н, t, J = 5.5, 3-СH2); 4.16 (2Н, t, J = 6.6, Н-6); 6.66 (2Н, d, J = 9.0, Н-3,5 Ar);
7.38 (2Н, d, J = 9.0, Н-2,6 Ar); 7.55 (1Н, t, J = 2.6, CНAr)
1.63-1.67 (4H, m, 2-СH2(СH2)2); 1.82-1.84 (2H, m, 3-СH2СH2);
2.78 (2H, t, J = 5.6, 2-СН2); 3.22 (2H, td, J = 6.7, J = 2.7, Н-7); 3.29 (2H, t, J = 5.4, 3-СН2);
3.86, 3.87 (3H, s and 3H, s, ОСН3); 4.19 (2Н, t, J = 6.7, Н-6); 6.87 (1Н, d, J = 8.4, Н-5 Ar);
6.98 (1Н, d, J = 2.0, Н-2 Ar); 7.10 (1Н, dd, J = 8.4, J = 2.0, Н-6 Ar);
7.58 (1Н, t, J = 2.7, CНAr)
13d
13e
1.62-1.68 (4H, m, 2-СH2(СH2)2); 1.81-1.84 (2H, m, 3-СH2СH2); 2.78 (2H, t, J = 5.5, 2-СН2);
3.19 (2H, td, J = 6.9, J = 2.7, Н-7); 3.29 (2H, t, J = 5.7, 3-СН2); 4.17 (2Н, t, J = 6.9, Н-6);
5.96 (2Н, s, ОСН2); 6.81 (1Н, d, J = 8.0, Н-5 Ar); 6.96 (1Н, d, J = 1.6, Н-2 Ar);
6.98 (1Н, dd, J = 8.0, J = 1.6, Н-6 Ar); 7.54 (1Н, t, J = 2.7, CНAr)
1.62-1.66 (4H, m, 2-СH2(СH2)2); 1.81-1.83 (2H, m, 3-СH2СH2);
2.78 (2H, t, J = 5.6, 2-СН2); 3.26 (2H, td, J = 7.0, J = 2.7, Н-7);
3.29 (2H, t, J = 5.6, 3-СН2); 4.17 (2H, t, J = 7.0, Н-6);
6.45 (1Н, dd, J = 3.4, J = 1.8, Н-4 Het); 6.51 (1Н, d, J = 3.4, Н-3 Het);
7.39 (1Н, t, J = 2.7, CНHet); 7.49 (1Н, d, J = 1.8, Н-5 Het)
_______
1
* The H NMR spectra of compounds 10b,c,e were recorded in trifluoroacetic
acid–CD3COOD, the remaining compounds in CDCl3.
The signals of the protons of the methylene groups annelated with the thiophene ring, are practically
unchanged in comparable compounds (5-8 and 10-13). Some differences were observed for the signals of the
substituents 2-CH3 and 3-CH3 of compounds 10b,c,e: they are shifted relative to the analogous signals of
compound 5 to stronger field (by 0.2-0.3ppm).
Thus the interaction of the studied derivatives of 7,8-dihydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-
4(6H)-one 5-8 with aromatic aldehydes and furfural occurs exclusively at the C(8)H2 unit, which is probably
related to the influence of the electron acceptor C=N group.
EXPERIMENTAL
1
IR spectra were recorded on an IR Fourier 2000 instrument in KBr tablets, and H NMR spectra were
recorded with a Unity 400+ instrument (400 MHz) in CDCl3 (compounds 5-8) and in a trifluoroacetic acid–
CD3COOD mixture with HMDS internal standard.
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Melting points were measured on Boetius (Germany) and MELTEMP (USA) blocks. The purity of the
products and the course of reactions were controlled by TLC on Sorbfil (Russia) and Whatman® UV-254 plates
with 2:1 benzene–hexane (compounds 5 and 6) and 5:1 benzene–methanol (compounds 7 and 8).
2-Amino-4,5-dimethyl- (1), 2-Amino-4,5-tri- (2), 2-Amino-4,5-tetra- (3) and 2-Amino-3-ethoxy-
carbonyl-4,5-pentamethylenethiophene (4) were synthesized by a known method [12].
2,3-Dimethyl- (5) and 2,3-Tri- (6), 2,3-Tetra- (7), and 2,3-Pentamethylene-7,8-dihydropyrrolo-
[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-one (8) (General Method). Phosphorus oxychloride (720 mmol, ρ = 1.80
g/cm3) was added dropwise during 0.5 h to a ice-cooled mixture of a substituted thiophene 1-4 (200 mmol) and
γ-butyrolactam (300 mmol). The reaction mixture was kept for 2 h in a water bath, then for 16 h at room
temperature, then poured into crushed ice and made basic to pH 9 with ammonia solution. The precipitate was
filtered off, washed several times with water, dried, and recrystallized from the corresponding solvent.
Compound 5. Yield 86%; mp 144-145°C (hexane) (mp 144-145°C [10]), Rf 0.70. 1H NMR spectrum, δ,
ppm (J, Hz): 2.18-2.24 (2H, m, H-7); 2.30 (3H, s, 2-CH3); 2.41 (3H, s, 3-CH3); 3.07 (2H, t, J = 8.1, H-8); 4.10
(2H, t, J = 7.1, H-6).
Compound 6. Yield 90%; mp 202-204°C (methanol) (mp 200°-201°C [4]), Rf 0.65. 1H NMR spectrum,
δ, ppm (J, Hz): 2.19-2.25 (2H, m, H-7); 2.35-2.41 (2H, m, 2-CH2CH2); 2.87 (2H, t, J = 7.1, 2-CH2); 3.0 (2H, t,
J = 7.1, 3-CH2); 3.10 (2H, t, J = 8.0, H-8); 4.11 (2H, t, J = 7.2, H-6).
1
Compound 7. Yield 82%; mp 215-217°C (ethanol) (mp 212-214°C [4]), Rf 0.43. H NMR spectrum, δ,
ppm (J, Hz): 1.75-1.81 (4H, m, 2-CH2(CH2)2); 2.19-2.24 (2H, m, H-7); 2.69 (2H, t, J = 5.8, 2-CH2); 2.94 (2H, t,
J = 6.2, 3-CH2); 3.07 (2H, t, J = 7.9, H-8); 4.09 (2H, t, J = 7.3, H-6).
Compound 8. Yield 96%; mp 156-158°C (heptane) (mp 156-158°C [4]), Rf 0.74. 1H NMR spectrum, δ,
ppm (J, Hz): 1.59-1.62 (4H, m, 2-CH2(CH2)2); 1.82 (2H, m, 3-CH2CH2); 2.18-2.24 (2H, m, H-7); 2.76 (2H, t,
J = 5.7, 2-CH2); 3.07 (2H, t, J = 7.9, H-8); 3.27 (2H, t, J = 5.7, 3-CH2); 4.10 (2H, t, J = 7.3, H-6).
2,3-Dimethyl- (10a-e) and 2,3-Trimethylene- (11a-e), 2,3-Tetramethylene- (12a-e) and 2,3-Penta-
methylene-substituted 8-Arylidenedihydropyrrolo[1,2-a]thieno[2,3-d]pyrimidin-4-ones (13a-e) (General
Method). A substituted dihydropyrrolopyrimidinone 5-8 (2.0 mmol) and an aldehyde 9a-e (2.0 mmol) were
added to a solution of NaOH (0.6 mmol) in ethanol (10 ml). The mixture was heated on a water bath for 7-8 h.
The solvent was evaporated off and the residue was recrystallized from benzene or a 2:1 benzene–hexane
mixture (in the case of product 11e).
REFERENCES
1.
2.
R. G. Melik-Ogandzhanyan, V. E. Khachatryan, and A. S. Gapoyan, Uspekhi Khimi, 54, 450 (1985).
M. Shodiev, B. A. Urakov, N. I. Mukarramov, and Kh. M. Shakhidoyatov, Khim. Geterotsikl. Soed.,
1574 (1993). [Chem. Heterocycl. Comp., 29, 1358 (1993)].
3.
M. V. Kapustin, I. A. Kharizomenova, V. I. Shvedov, T. P. Radkevich, and L. D. Shipilova, Pharm.
Chem. J., 26, 73 (1992).
4.
5.
K. Csukonyi, J. Lazar, G. Bernath, L. Hermecz, and Z. Meszaros, Monatsh. Chem., 117, 1295 (1986).
P. Blaskiewich, H. Vorbrueggen, and H. Koch, Ger. Offen. DE 2411273, Chem. Abstr., 83, 206324
(1975).
6.
S. Gerd, L. Wilfried, B. Alferd, E. Franz, W. Karsten, H. T. Juergen, B. Berthold, K. Frank, and
C. Sharon. Ger. Offen. DE 19636769. Chem Abstr., 128, 217381 (1998).
A. Lilienkampf, S. Heikkinen, I Mutikainen, and K. Wähälä, Synthesis, 2699 (2007).
S. Sasaki, N. Cho, Y. Nara, M. Harada, S. Endo, N. Suzuki, S. Furuya, and M. Fujino, J. Med. Chem.,
46, 113 (2003).
7.
8.
1398

9.
S. Moore, H. Jaeschke, G. Kleinau, S. Neumann, S. Costanzi, J.-K. Jiang, J. Childress, B. M. Raaka,
A. Colson, R. Paschke, G. Krause, C. J. Thomas, and M. C. Gershengorn, J. Med. Chem., 49, 3888
(2006).
10.
V. I. Shvedov, I. A. Kharizomenova, and A. N. Grinev, Khim. Geterotsikl. Soed., 765 (1975). [Chem.
Heterocycl. Comp., 11, 664 (1975)].
11.
12.
13.
14.
15.
16.
17.
Kh. M. Shakhidoyatov, Diss. Doct. Chem. Sci., Moscow, 1983, 232 pp.
K. Gewald, E. Schinke, and H. Böttcher, Chem. Ber., 99, 94 (1966).
N. P. Peet, S. Sunder, R. J. Barbuch, and A. P. Vinogradoff, J. Heterocycl. Chem.,23, 192 (1986).
M. V. Bhatt and P. T. Perumal, Tetrahedron Lett., 22, 2605 (1981).
F. M. Hauser, and S. R. Ellenberger, Synthesis, 723 (1987).
C. M. Marson, Tetrahedron, 48, 3659 (1972).
Á. Horváth, H. István, L. Vasvári-Debreczy, S. Kálmán, M. Pongor-Csákvári, and Z. Mészáros, J. Chem.
Soc., Perkin Trans. I, 369 (1983).
18.
19.
20.
21
Kh. M. Shakhidoyatov, M. Ya. Yamankulov, and Ch. Sh. Kadyrov, Khimiya Prirod. Soed., 552 (1977).
Kh. M. Shakhidoyatov and I. Kaisarov, Khimiya Prirod. Soed., 79 (1998).
A. Sh. Abdurazakov, B. Zh. Elmuradov, and Kh. M. Shakhidoyatov, Uzb. Khim. Zh., 6, 46 (2007).
B. Zh. Elmuradov, A. Sh. Abdurazakov, and Kh. M. Shakhidoyatov, Khimiya Prirod. Soed., 383 (2008).
A. Sh. Abdurazakov, B. Zh. Elmuradov. Zh. E. Turdibaev, and Kh. M. Shakhidoyatov, Khimiya Prirod.
Soed., 342 (2009).
22.
23.
24
Kh. A. Bozorov, B. Zh. Elmuradov, and Kh. M. Shakhidoyatov in: Papers of the Scientific-technological
Conference "Current Questions of the Education, Science, and Production in Pharmacy", Tashkent,
2008, p. 379.
B. Zh. Elmuradov, Kh. A. Bozorov, and Kh. M. Shakhidoyatov in: "Conference on Current Problems in
the Chemistry of Natural Products", Tashkent, 2009, p. 93.
25.
26.
Á. Horváth, H. István, M. Pongor-Csákvári, and Z. Mészáros, J. Heterocycl. Chem., 21, 219 (1984).
E. Oripov, Kh. M. Shakhidoyatov, Ch. Sh. Kadyrov, and N. D. Abdullaev, Khim. Geterotsikl. Soed., 684
(1979). [Chem. Heterocycl. Comp., 15, 556 (1979)].
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