Facile approach to the synthesis of substituted thieno[2,3-d]pyrimidin-4- ones

Article abstract of DOI:10.1515/hc-2012-0095

Condensation of Gewald's thiophenes substituted with a dimethylaminomethyleneamino group at position 2 with primary amines yields 5/6-aryl-thieno[2,3-d] pyrimidin-4-ones with variable substituents at the N3 position.

Full text of DOI:10.1515/hc-2012-0095

ꢁꢁꢁꢂ
DOI 10.1515/hc-2012-0095ꢀ ꢀ Heterocycl. Commun. 2012; 18(5-6): 253–256
Anna Hovhannisyan*, Lilit Aristakesyan and Gagik Melikyan
Facile approach to the synthesis of substituted
thieno[2,3-d]pyrimidin-4-ones
Abstract: Condensation of Gewald’s thiophenes substi- the corresponding new dimethylaminomethyleneamino
tutedwithadimethylaminomethyleneaminogroupatposi- derivatives 2a–e in high yields (up to 97%).
tion 2 with primary amines yields 5/6-aryl-thieno[2,3-d]
pyrimidin-4-ones with variable substituents at the N3
position.
A subsequent treatment of the intermediate products
2 with primary amines in xylenes under reflux conditions
furnished substituted thieno[2,3-d]pyrimidin-4-ones 3a–r
with yields up to 87%. The highest yields were obtained
with the 1:3 molar ratio of the intermediate product 2 to
the primary amine. Elimination of gaseous dimethyl-
amine was used to monitor the progress of the reaction.
The first step of this synthesis apparently involves addi-
tion of the amine to the methyleneamino functionality of
2. The observed high yields of the final products 3 show
that a possible reaction of the amine with the ester func-
tion of 2 is not a problem.
The products 3a–r contain a substituted alkyl group
at the ring position N3. This group is derived from the
aliphatic amine. The synthesis of an aromatic analog 3s
by the reaction of 2b with p-anisidine required the use of
acetic acid as a solvent. Product 3s was obtained in low
yield, and attempted reactions with other anilines were
not successful.
Keywords: amines; cyclocondensation; enamines;
Gewald’s reaction; thieno[2,3-d]pyrimidin-4-ones.
* Corresponding author: Anna Hovhannisyan, Yerevan State
University, Alex Manoogian 1, 0025 Yerevan, Armenia,
e-mail: annahovh@gmail.com
Lilit Aristakesyan: Yerevan State University, Alex Manoogian 1, 0025
Yerevan, Armenia
Gagik Melikyan: Yerevan State University, Alex Manoogian 1, 0025
Yerevan, Armenia
Introduction
Thienopyrimidines have been shown to possess a variety
of pharmacological activities including analgesic, anti-
inflammatory, antipyretic, antimicrobial, anticonvul-
sant, fungicidal, and antiplatelet properties (Ibrahim
et al., 1996; Varvounis and Giannopoulos, 1996). Several
derivatives are also central nervous system agents (Sharma
et al., 2010) and inhibitors of Cyclin D1-CDK4 (Horiuchi
et al., 2009). Several 6-(4-chlorophenyl)-3-substituted
thieno[3,2-d]pyrimidin-4(3H)-ones with aromatic and het-
erocyclic substituents are melanin-concerning hormone
receptoragonists(Tavaresetal.,2006).Earlierwedescribed
Conclusions
Readily available enamines 2 are useful intermediate
products in the synthesis of substituted thieno[2,3-d]
pyrimidin-4-ones 3 that contain a primary group at the N3
position.
a
convenient method for synthesis of thieno[2,3-d]
Experimental section
pyrimidin-4-ones substituted with aliphatic groups
(Hovhannisyan et al., 2004) at the ring atom N3. Now
we enhance this chemistry by the synthesis of 5- and
6-aromatically substituted derivatives 3a–s (Scheme 1).
General
Melting points were determined on an SMP-10 melting point appara-
1
tus and are uncorrected. H NMR spectra were obtained on a Varian
Mercury 300 VX spectrometer at 300 MHz with tetramethylsilane as
internal reference in DMSO-d6 solution at 303 K. Thin layer chroma-
tography analysis was performed on Silufol-250 UV plates eluting
with acetone/benzene (1:3); detection was with UV light at 254 nm and
iodine vapors. The 2-aminothiophene 1a was synthesized by 3-com-
Results and discussion
Readily available Gewald’s 2-aminothiophenes 1a–e were
allowed to react with N,N′-dimethylformamide dimethyl-
acetal (DMF/DMA) in boiling anhydrous xylenes to give ponent Gewald’s reaction of phenylacetaldehyde, ethyl cyanoacetate,
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254ꢀ
ꢀA. Hovhannisyan et al.: Thieno[2,3-d]pyrimidin-4-ones
O
O
R2
O
N
R2
R1
R2
R1
OEt
OEt
NH2
R3
DMF/DMA
Xylene
Me NH2R3
N
R1
N
N
Δ
S
S
S
Me
Δ
, 7 h
1a-e
2a-e
3a-s
1a, 2a: R1 = Ph, R2 = H
1b, 2b: R1 = H, R2 = Ph
3h: R1 = H, R2 = Ph, R3 = CH2CH2C6H5
3i: R1 = H, R2 = Ph, R3 = 4-CH2CH2C6H4F
R1 = H, R2 = 4-C6H4CH3
R1 = H, R2 = 4-C6H4Cl
R1 = H, R2 = Ph, R3 = 3-(2-methylpiperidino)propyl
R1 = H, R2 = 4-C6H4CH3, R3 = 4-CH2C6H4OCH3
R1 = H, R2 = 4-C6H4CH3, R3 = 3-Pyridylmethyl
1c 2c
3j
:
,
,
:
:
:
1d 2d
3k
:
3l
:
R1 = H, R2 = Naphthalen-2-yl
1e 2e
,
3a: R1 = Ph, R2 = H, R3 = 2-Furylmethyl
3m: R1 = H, R2 = 4-C6H4CH3, R3 = (tetrahydrofuran-2-yl)methyl
3b: R1 = Ph, R2 = H, R3 = 4-CH2CH2C6H4OCH3 3n: R1 = H, R2 = 4-C6H4CH3, R3 = 2-Thienylmethyl
:
:
R1 = Ph, R2 = H, R3 = CH2CH2OH
R1 = H, R2 = Ph, R3 = CH2C6H5
R1 = H, R2 = Ph, R3 = 4-CH2C6H4F
:
R
1 = H, R2 = 4-C6H4Cl, R3 = 4-CH2CH2C6H4OCH3
R1 = H, R2 = 4-C6H4Cl, R3 = 3-Pyridylmethyl
1 = H, R2 = Naphthalen-2-yl, R3 = 4-CH2CH2C6H4F
1 = H, R2 = Ph, R3 = 4-C6H4OCH3
3c
3o
3p
3d
:
3e
3r
:
:
R
R
3f:
R
1 = H, R2 = Ph, R3 = 2-Furylmethyl
3s:
3g: R1 = H, R2 = Ph, R3 = 2-Thienylmethyl
Scheme 1ꢀThe synthesis of substituted thieno[2,3-d]pyrimidin-4-ones.
and sulfur. The 2-component reaction with arylidenecyanoacetates C, 57.05; H, 5.09; Cl, 10.53; N, 8.32; S, 9.52. Found: C, 56.70; H, 5.02; Cl,
was used in the preparation of compounds 1b–e, as described previ- 10.40; N, 8.24; S, 9.41.
ously (Gewald, 1966).
Ethyl 2-(dimethylaminomethyleneamino)-4-(naphthalen-2-yl)
thiophene-3-carboxylate (2e)ꢀYield 95%; mp 104°C; 1H NMR:
δ 1.02 (t, J = 7.1 Hz, 3H), 3.05 (s, 3H), 3.13 (s, 3H), 4.03 (q, J = 7.1 Hz,
2H), 6.62 (s, 1H), 7.38–7.46 (m, 3H), 7.73–7.84 (m, 5H). Anal. Calcd for
General procedure for synthesis of
ethyl
C20H20N2O2S: C, 68.16; H, 5.72; N, 7.95; S, 9.10. Found: C, 67.80; H, 5.65;
N, 7.83; S, 8.98.
2-(Dimethylaminomethyleneamino)thiophene-3-carboxylates
2a–eꢀA mixture of a thiophene 1a–e (10 mmol) and DMF/DMA
(1.56 mL, 12 mmol) in anhydrous xylenes (20 mL) was heated under
General procedure for the synthesis
reflux for 7 h. Afer cooling to room temperature 5 mL of light petro-
of substituted thieno[2,3-d]
leum was added, and the precipitated crystals of 2a–e were filtered,
washed with diethyl ether, and dried.
pyrimidin-4(3H)-ones 3a–r
A mixture of 2a–e (5 mmol) and primary amine (15 mmol) in an an-
hydrous xylenes (20 mL) was heated under reflux for 30 h. Afer cool-
ing to room temperature the solution was treated with 8 mL of light
petroleum. The precipitated crystals of 3a–r were filtered, washed
with diethyl ether, and dried under reduced pressure.
Ethyl 2-(dimethylaminomethyleneamino)-5-phenyl-thiophene-
1
3-carboxylate (2a)ꢀYield 94%; mp 80°C; H NMR: δ 1.05 (t, J = 7.1
Hz, 3H), 3.04 (s, 3H), 3.11 (s, 3H), 4.01 (q, J = 7.1 Hz, 2H), 6.44 (s, 1H),
7.15–7.38 (m, 5H), 7.76 (s, 1H). Anal. Calcd for C16H18N2O2S: C, 63.55;
H, 6.00; N, 9.26; S, 10.60. Found: C, 63.12; H, 6.03; N, 9.14; S, 10.48.
Ethyl 2-(dimethylaminomethyleneamino)-4-phenylthiophene-
1
3-(2-Furylmethyl)-6-phenylthieno[2,3-d]pyrimidin-4(3H)-one
(3a)ꢀYield 53%; mp 200°C; IR: 1657, 1688 cm-1; 1H NMR: δ 5.23 (s, 2H),
6.35 (dd, J = 3.1 Hz, 1.9 Hz, 1H), 6.45 (dd, J = 3.1 Hz, 0.8 Hz, 1H), 7.28–
7.35 (m, 1H), 7.35–7.43 (m, 2H), 7.44 (dd, J = 1.9 Hz, 0.8 Hz, 1H), 7.63–7.68
(m, 3H), 8.35 (s,1H). Anal. Calcd for C17H12N2O2S: C, 66.22; H, 3.92; N,
9.08; S, 10.40. Found: C, 65.84; H, 3.84; N, 8.95; S, 10.36.
3-carboxylate (2b)ꢀYield 95%; mp 95°C; H NMR: δ 1.05 (t, J = 7.1
Hz, 3H), 3.04 (s, 3H), 3.11 (s, 3H), 4.03 (q, J = 7.1 Hz, 2H), 6.48 (s, 1H),
7.17–7.37 (m, 5H), 7.73 (s, 1H). Anal. Calcd for C16H18N2O2S: C, 63.55;
H, 6.00; N, 9.26; S, 10.60. Found: C, 63.16; H, 5.92; N, 9.15; S, 10.48.
Ethyl 2-(dimethylaminomethyleneamino)-4-p-tolylthiophene-
1
3-carboxylate (2c)ꢀYield 92%; mp 75°C; H NMR: δ 1.09 (t, J = 7.1
3-[2-(4-Methoxyphenyl)ethyl]-6-phenylthieno[2,3-d]pyrimidin-
Hz, 3H), 2.36 (s, 3H), 3.02 (s, 3H), 3.11 (s, 3H), 4.04 (q, J = 7.1 Hz, 2H),
6.45 (s, 1H), 7.03–7.20 (m, 4H), 7.71 (s, 1H). Anal. Calcd for C17H20N2O2S:
C, 64.53; H, 6.37; N, 8.85; S, 10.13. Found: C, 64.30; H, 6.28; N, 8.76;
S, 9.95.
1
4(3H)-one (3b)ꢀYield 59%; mp 174°C; IR: 1650, 1696 cm-1; H NMR:
δ 2.97 (t, J = 7.3 Hz, 2H), 3.76 (s, 3H), 4.14–4.21 (t, J = 7.3 Hz, 2H), 6.76–
6.83 (m, 2H), 7.10–7.15 (m, 2H), 7.28–7.45 (m, 3H), 7.65–7.70 (m, 2H), 7.70
(s, 1H), 8.02 (s, 1H). Anal. Calcd for C21H18N2O2S: C, 69.59; H, 5.01; N,
7.73; S, 8.85. Found: C, 69.34; H, 4.93; N, 7.66; S, 8.76.
Ethyl 4-(4-chlorophenyl)-2-(dimethylaminomethyleneamino)
thiophene-3-carboxylate (2d)ꢀYield 92%; mp 98°C; 1H NMR: δ 1.10
(t, J = 7.1 Hz, 3H), 3.03 (s, 3H), 3.11 (s, 3H), 4.04 (q, J = 7.1 Hz, 2H), 6.51 3-(2-Hydroxyethyl)-6-phenylthieno[2,3-d]pyrimidin-4(3H)-one
(s, 1H), 7.20–7.32 (m, 4H), 7.72 (s, 1H). Anal. Calcd for C16H17ClN2O2S: (3c)ꢀYield 39%; mp 156°C; IR: 1655, 1693, 3302, 3363 cm-1; H NMR:
1
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A. Hovhannisyan et al.: Thieno[2,3-d]pyrimidin-4-onesꢀ
ꢀ255
3-(3-Pyridylmethyl)-5-p-tolylthieno[2,3-d]pyrimidin-4(3H)-one
δ 3.70 (q, J = 5.2 Hz, 2H), 4.07 (t, J = 5.2 Hz, 2H), 4.72 (t, J = 5.2 Hz, 1H),
7.31 (m, 1H), 7.41 (m, 2H), 7.66 (m, 2H), 7.66 (s, 1H); 8.16 (s, 1H). Anal.
Calcd for C14H12N2O2S: C, 61.75; H, 4.44; N, 10.29; S, 11.77. Found: C,
61.53; H, 4.37; N, 10.20; S, 11.64.
1
(3l)ꢀYield 55%, mp 145°C; IR: 1657, 1689 cm-1; H NMR: δ 2.38 (s,
3H), 5.23 (s, 2H), 7.11 (m, 2H), 7.14 (s, 1H), 7.22 (ddd, J = 7.6 Hz, 4.8 Hz,
1.2 Hz, 1H), 7.34 (m, 2H), 7.37 (dt, J = 7.8 Hz, 1.1 Hz, 1H), 7.69 (ddd,
J = 7.8 Hz, 1.8 Hz, 1H), 8.43 (s, 1H), 8.48 (ddd, J = 4.8 Hz, 1.8 Hz, 1.1
Hz, 1H). Anal. Calcd for C19H15N3OS: C, 68.45; H, 4.53; N, 12.60; S, 9.62.
Found: C, 68.31; H, 4.56; N, 12.51; S, 9.51.
3-Benzyl-5-phenyl-thieno[2,3-d]pyrimidin-4(3H)-one (3d)ꢀYield
1
50%; mp 168°C; IR: 1661, 1697 cm-1; H NMR: δ 5.19 (s, 2H), 7.19–7.42
(m, 9H), 7.49 (dd, J = 7.7 Hz, 1.7 Hz, 2H), 8.51 (s, 1H). Anal. Calcd for
C19H14N2OS: C, 71.67; H, 4.43; N, 8.80; S, 10.07. Found: C, 71.27; H, 4.38;
N, 8.62; S, 10.00.
[3-(Tetrahydrofuran-2-yl)methyl]-5-p-tolylthieno[2,3-d]pyrimi-
din-4(3H)-one (3m)ꢀYield 76%; mp 117°C; IR: 1648, 1691 cm-1;
1H NMR: δ 1.54–1.67 (m, 1H), 1.80–2.10 (m, 3H), 2.40 (s, 3H), 3.65–3.76
(m, 1H), 3.76–3.90 (m, 2H), 4.05–4.15 (m, 1H), 4.23 (dd, J = 13.4 Hz,
3.1 Hz, 1H), 7.10–7.16 (m, 3H), 7.34–7.40 (m, 2H), 8.18 (s, 1H). Anal.
Calcd for C18H18N2O2S: C, 66.23; H, 5.56; N, 8.58; S, 9.82. Found: C,
65.83; H, 5.49; N, 8.48; S, 9.71.
3-(4-Fluorobenzyl)-5-phenylthieno[2,3-d]pyrimidin-4(3H)-one
(3e)ꢀYield 72%; mp 171°C; IR: 1647, 1698 cm-1; 1H NMR: δ 5.16 (s, 2H),
6.97–7.07 (m, 2H), 7.23 (s, 1H), 7.29–7.39 (m, 3H), 7.43–7.52 (m, 4H), 8.56
(s, 1H). Anal. Calcd for C19H13FN2OS: C, 67.84; H, 3.90; F, 5.65; N, 8.33;
S, 9.53. Found: C, 67.46; H, 3.91; F, 5.59; N, 8.22; S, 9.42.
3-(2-Thienylmethyl)-5-p-tolylthieno[2,3-d]pyrimidin-4(3H)-one
(3n)ꢀYield 72%; mp 178°C; IR: 1645, 1690 cm-1; 1H NMR: δ 2.41 (s, 3H),
5.35 (s, 2H), 6.92 (dd, J = 5.1 Hz, 3.5 Hz, 1H), 7.13–7.18 (m, 3H), 7.20 (dd,
J = 3.5 Hz, 1.1 Hz, 1H), 7.26 (dd, J = 5.1 Hz, 1.1 Hz, 1H), 7.36–7.41 (m,
2H), 8.50 (s, 1H). Anal. Calcd for C18H14N2OS2: C, 63.88; H, 4.17; N, 8.28;
S, 18.95. Found: C, 63.42; H, 4.02; N, 8.21; S, 18.79.
3-(2-Furylmethyl)-5-phenylthieno[2,3-d]pyrimidin-4(3H)-one
(3f)ꢀYield 67%; mp 181°C; IR: 1652, 1690 cm-1; 1H NMR: δ 5.19 (s, 2H,
CH2), 6.33 (dd, J = 3.2 Hz, 1.9 Hz, 1H), 6.42 (dd, J = 3.2 Hz, 0.8 Hz, 1H),
7.22 (s, 1H), 7.30–7.38 (m, 3H), 7.43 (dd, J = 1.9 Hz, 0.8 Hz, 1H), 7.45–7.51
(m, 2H), 8.40 (s, 1H). Calcd for C17H12N2O2S: C, 66.22; H, 3.92; N, 9.08; S,
10.40. Found: C, 65.75; H, 3.85; N, 9.03; S, 10.28.
5-(4-Chlorophenyl)-3-(4-methoxyphenethyl)thieno[2,3-d]
pyrimidin-4(3H)-one (3o)ꢀYield 61%; mp 114°C; IR: 1657, 1691
5-Phenyl-3-(2-thienylmethyl)thieno[2,3-d]pyrimidin-4(3H)-one
(3g)ꢀYield 65%; mp 179°C; IR: 1659, 1697 cm-1; 1H NMR: δ 5.36 (s, 2H),
6.92 (dd, J = 5.1 Hz, 3.5 Hz, 1H), 7.20 (dd, J = 3.5 Hz, 1.1 Hz, 1H), 7.24 (s,
1H), 7.27 (dd, J = 5.1 Hz, 1.1 Hz, 1H), 7.30–7.40 (m, 3H), 7.48–7.54 (m,
2H), 8.53 (s, 1H). Anal. Calcd for C17H12N2OS2: C, 62.94; H, 3.73; N, 8.63;
S, 19.77. Found: C, 62.63; H, 3.74; N, 8.55; S, 19.64.
1
cm-1; H NMR: δ 3.75 (s, 3H), 5.10 (s, 2H), 6.77–6.84 (m, 2H), 7.24 (s,
1H), 7.31–7.38 (m, 4H), 7.46–7.51 (m, 2H), 8.49 (s, 1H). Anal. Calcd for
C21H17ClN2O2S: C, 63.55; H, 4.32; Cl, 8.93; N, 7.06; S, 8.08. Found: C,
63.13; H, 4.34; Cl, 8.88; N, 6.98; S, 8.02.
5-(4-Chlorophenyl)-3-[(3-pyridyl)methyl]thieno[2,3-d]pyrimi-
1
din-4(3H)-one (3p)ꢀYield 47%; mp 145°C; IR: 1655, 1688 cm-1; H
3-Phenethyl-5-phenylthieno[2,3-d]pyrimidin-4(3H)-one
NMR: δ 5.24 (s, 2H), 7.22 (ddd, J = 7.6 Hz, 4.9 Hz, 1.0 Hz, 1H), 7.26
(s, 1H), 7.31 (m, 2H), 7.38 (dt, J = 7.8 Hz, 1.0 Hz, 1H), 7.46 (m, 2H), 7.70
(ddd, J = 7.8 Hz, 7.6 Hz, 1.8 Hz, 1H), 8.46 (s, 1H), 8.48 (ddd, J = 4.9 Hz,
1.8 Hz, 1.0 Hz, 1H). Anal. Calcd for C18H12ClN3OS: C, 61.10; H, 3.42; Cl,
10.02; N, 11.88; S, 9.06. Found: C, 61.15; H, 3.39; Cl, 9.91; N, 11.76; S,
8.99.
1
(3h)ꢀYield 45%; mp 128°C; IR: 1662, 1688 cm-1; H NMR: δ 2.94–3.08
(m, 2H), 4.12–4.28 (m, 2H), 7.15–7.32 (m, 6H), 7.31–7.41 (m, 3H), 7.48–
7.54 (m, 2H), 8.12 (s, 1H). Anal. Calcd for C20H16N2OS: C, 72.26; H, 4.85;
N, 8.43; S, 9.65. Found: C, 72.02; H, 4.80; N, 8.36; S, 9.68.
3-[2-(4-Fluorophenyl)ethyl]-5-phenylthieno[2,3-d]pyrimidin-
1
4(3H)-one (3i)ꢀYield 53%; mp 143°C; IR: 1660, 1695 cm-1; H NMR:
3-(4-Fluorophenethyl)-5-(naphthalen-2-yl)thieno[2,3-d]pyrimi-
δ 2.96–3.03 (m, 2H), 4.17 (dd, J = 8.3 Hz, 6.8 Hz, 2H), 6.94–7.05 (m, 2H),
7.21 (s, 1H), 7.22–7.28 (m, 2H), 7.30–7.40 (m, 3H), 7.48–7.53 (m, 2H), 8.15
(s, 1H). Anal. Calcd for C20H15FN2OS: C, 68.55; H, 4.31; F, 5.42; N, 7.99;
S, 9.15. Found: C, 68.17; H, 4.25; F, 5.36; N, 8.03; S, 9.05.
1
din-4(3H)-one (3r)ꢀYield 61%; mp 110°C; IR: 1648, 1687 cm-1; H
NMR: δ 3.00 (m, 2H), 4.19 (m, 2H), 6.99 (m, 2H), 7.25 (m, 2H), 7.35 (s,
1H), 7.44–7.51 (m, 2H), 7.65 (dd, J = 8.5 Hz, 1.8 Hz, 1H), 7.84 (d, J = 8.5
Hz, 1H), 7.83–7.91 (m, 2H), 7.99 (d, J = 1.8 Hz, 1H), 8.18 (s, 1H). Anal.
Calcd for C24H17FN2OS: C, 71.98; H, 4.28; F, 4.74; N, 6.99; S, 8.01. Found:
C, 71.49; H, 4.25; F, 4.68; N, 6.91; S, 7.93.
3-[3-(2-Methylpiperidino)propyl]-5-phenylthieno[2,3-d]pyrimi-
din-4(3H)-one (3j)ꢀYield 57%; mp 73°C; IR: 1647, 1696 cm-1; 1H NMR:
δ 1.00 (d, J = 6.3 Hz, 3H), 1.28 (m, 2H), 1.44–1.65 (m, 4H), 1.75–1.95
(m, 2H), 2.03 (ddd, J = 11.4 Hz, 9.2 Hz, 3.5 Hz, 1H), 2.20 (m, 1H), 2.28
(m, 1H), 2.69–2.77 (m, 2H), 3.93(m, 1H), 4.03 (m, 1H), 7.20 (s, 1H), 7.29–
7.38 (m, 3H), 7.46–7.51 (m, 2H), 8.29 (s, 1H). Anal. Calcd for C21H25N3OS:
C, 68.63; H, 6.86; N, 11.43; S, 8.72. Found: C, 68.31; H, 6.81; N, 11.37;
S, 8.61.
Synthesis of 3-(4-methoxyphenyl)-5-phenylthieno[2,3-d]pyrimi-
din-4(3H)-one (3s)ꢀA mixture of 2b (1g, 3.3 mmol) and p-anisidine
(0.41 g, 3.3 mmol) in glacial acetic acid (10 mL) was heated under
reflux for 30 h, then cooled and treated with 8 mL of light petro-
leum. The precipitated crystals of 3s were filtered, washed with di-
ethyl ether, and dried under reduced pressure: Yield 0.36 g (32%);
1
mp 162°C; IR: 1642, 1691 cm-1; H NMR: δ 3.86 (s, 3H), 7.02 (d, J = 8.9
3-(4-Methoxybenzyl)-5-p-tolylthieno[2,3-d]pyrimidin-4(3H)-
Hz, 2H), 7.37–7.24 (m, 6H), 7.50 (dd, J = 7.5 Hz, 1.7 Hz, 2H), 8.16 (s, 1H).
Anal. Calcd for C19H14N2O2S: C, 68.25; H, 4.22; N, 8.38; S, 9.59. Found:
C, 67.87; H, 4.15; N, 8.31; S, 9.52.
1
one (3k)ꢀYield 72%; mp 140°C; IR: 1651, 1693 cm-1; H NMR: δ
2.40 (s, 3H), 3.75 (s, 3H), 5.09 (s, 2H), 6.77–6.84 (m, 2H), 7.11–7.18
(m, 3H), 7.29–7.40 (m, 4H), 8.46 (s, 1H). Anal. Calcd for C21H18N2O2S:
C, 69.59; H, 5.01; N, 7.73; S, 8.85. Found: C, 69.45; H, 5.04; N, 7.61;
S, 8.80.
Received June 11, 2012; accepted August 28, 2012; previously
published online November 16, 2012
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256ꢀ
ꢀA. Hovhannisyan et al.: Thieno[2,3-d]pyrimidin-4-ones
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