Synthesis of some new pyrimidine selanyl derivatives

Article abstract of DOI:10.1080/10426507.2018.1424165

The targeted synthesis of 2-(methylsulfanyl)-6-(furan-2-yl)-4(3H)-selenoxo -pyrimidine-5-carbonitrile failed due to the formation 1-methyl-2-methylsulfanyl-6-oxo -4-(furan-2-yl)-1,6-dihydropyrimidine-5-carbonitrile. A new series of 5,6,7,8-tetrahydro-1-benzo thieno[2,3-d]pyrimidine-4-yl substituted selanyl derivatives were prepared by the reaction of sodium diselenide with 4-chloro-5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine followed by the reaction with chloroacetic acid derivatives such as ethyl chloroacetate, chloroacetamide or chloroacetonitrile. Hydrazinolysis of ethyl (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine- 4-ylselanyl)acetate with hydrazine hydrate gave the corresponding hydrazino derivative. The latter reacted with ethyl acetoacetate, acetylacetone, diethyl malonate, ethoxymethylenemalononitrile or ethyl 2-cyano-3-ethoxyacetate to afford 5-methyl-2-[2-(5,6,7,8-tetrahydro-1-benzothieno [2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazol-3-one, 1-(3,5-dimethylpyrazol-1-yl)-2- (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)ethanone, 1-[2-(5,6,7,8-tetrahydro -1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazolidine-3,5-dione and 5-Amino-1-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)acetyl]-1H-pyrazol -4-yl substituted carbonitrile or ethyl carboxylate, respectively. The structure of the novel compounds was confirmed by spectroscopic tools (IR, ¹H NMR ¹³C NMR and mass spectra) and elemental analysis.

Full text of DOI:10.1080/10426507.2018.1424165

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Synthesis of some new
pyrazolobenzothienopyrimidineselanyl derivatives
Refaah A. Alshahrani, Adel A. Gobouri, Naif A. Alshanbari, Saleh A. Ahmed &
Shams H. Abdel-Hafez
To cite this article: Refaah A. Alshahrani, Adel A. Gobouri, Naif A. Alshanbari, Saleh A. Ahmed
& Shams H. Abdel-Hafez (2018): Synthesis of some new pyrazolobenzothienopyrimidineselanyl
derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:
10.1080/10426507.2018.1424165
To link to this article: https://doi.org/10.1080/10426507.2018.1424165
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Date: 08 January 2018, At: 03:52

ACCEPTED MANUSCRIPT
Synthesis of some new pyrazolobenzothienopyrimidineselanyl derivatives
Refaah A. Alshahrani,a Adel A. Gobouri,a Naif A. Alshanbari,a Saleh A. Ahmed,b and
Shams H. Abdel-Hafez.a,c [1]
a Department of Chemistry, Faculty of Science, Taif University, Taif KSA;
b Department of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah KSA;
c Department of Chemistry, Faculty of Science, Assiut University, Assiut Egypt.
Abstract – The targeted synthesis of 2-(methylsulfanyl)-6-(furan-2-yl)-4(3H)-selenoxo -
pyrimidine-5-carbonitrile failed due to the formation 1-methyl-2-methylsulfanyl-6-oxo -4-(furan-
2-yl)-1,6-dihydropyrimidine-5-carbonitrile.
A
new series of 5,6,7,8-tetrahydro-1-benzo
thieno[2,3-d]pyrimidine-4-yl substituted selanyl derivatives were prepared by the reaction of
sodium diselenide with 4-chloro-5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine followed by
the reaction with chloroacetic acid derivatives such as ethyl chloroacetate, chloroacetamide or
chloroacetonitrile. Hydrazinolysis of ethyl (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine-
4-ylselanyl)acetate with hydrazine hydrate gave the corresponding hydrazino derivative. The
latter
reacted
with
ethyl
acetoacetate,
acetylacetone,
diethyl
malonate,
ethoxymethylenemalononitrile or ethyl 2-cyano-3-ethoxyacetate to afford 5-methyl-2-[2-
(5,6,7,8-tetrahydro-1-benzothieno [2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazol-3-
one,
1-(3,5-dimethylpyrazol-1-yl)-2-
(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-
-1-benzothieno[2,3-d]pyrimidine-4-
ylselanyl)ethanone,
1-[2-(5,6,7,8-tetrahydro
1 Contact: Shams H. Abdel-Hafez: shams@aun.edu.eg; shams_abdelhafez@yahoo.com
Chemistry Department, Faculty of Science, Taif University, Taif 21974, Saudi Arabia;
Department of Chemistry, Faculty of Science, Assiut University, Assiut, Egypt
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ylselanyl)acetyl]-2,4-dihydropyrazolidine-3,5-dione and 5-Amino-1-[2-(5,6,7,8-tetrahydro-1-
benzothieno[2,3-d]pyrimidin-4-ylselanyl)acetyl]-1H-pyrazol -4-yl substituted carbonitrile or
ethyl carboxylate, respectively. The structure of the novel compounds was confirmed by
spectroscopic tools (IR, 1H NMR 13C NMR and mass spectra) and elemental analysis.
Keywords: Benzothienopyrimidine diselenide; benzothienopyrimidine selanyl derivatives;
pyrazolbenzothienopyrimidine selanyl derivatives
INTRODUCTION
Pyrimidine derivatives play a vital role in many biological activities, e. g. in several vitamins and
purines such as uracil, thymine, and cytosine.1 According to the literature, pyrimidine derivatives
exhibit various pharmacological activities as antibacterial,2 antifungal,3 antiviral,4,5 anticancer,6,7
analgesic and anti-inflammatory drugs.8 In addition, thienopyrimidine derivatives show many
biological activities, such as anticancer,9 antiviral,10 antitumor,11 anti-inflammatory,12
antimicrobial,13 and antimalarial,14. Despite the high toxicity of many selenium compounds, they
show anti-viral, anti-microbial, anti-tumor15,16 and anti-cancer17,18 activity.19-27 Organoselenium
compounds have been tested as agents against bacteria, viruses, fungi, parasites, as antihistamines,
as well as anti-cancer drugs.28-35 Therefore, we decided to expand our investigations to introduce
selenium into pyrimidine derivatives, hoping to obtain a new series of heterocyclic systems with
the anticipated biological and pharmaceutical effects.
2
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RESULTS and DISCUSSION
To attain our target, the introduction of selenium into the pyrimidine ring, we started from
chlorobenzothienopyrimidine 6 which was prepared according to known methods.36, 37 The
reaction of cyclohexanone (1), elemental sulfur (2) and ethyl cyanoacetate (3) gave ethyl 2-
aminobenzothiophene-3-carboxylate 4. Refluxing of 4 with formamide led to the
benzothienopyrimidinone derivative 5, the reaction of which with a mixture of POCl3/ PCl5 gave
1
13
4-chloro-1-benzothieno[2,3-d]pyrimidine 6. The structure of 6 was confirmed by its H and C
NMR spectra and elemental analysis. The synthesis of the target compound 4,4'-bis(5,6,7,8-
tetrahydro-1-benzothieno[2,3-d]pyrimidine) diselenide (7) was achieved by the reaction of 6 with
sodium diselenide in ethanol/DMF (Scheme 1). The structure of 7 was established by elemental
analysis, 1H NMR, 13C NMR, IR and mass spectra. The IR spectrum showed absorptions at 1585
(C=N) cm–1. The 1H NMR data showed the characteristics signals at δ = 1.76-3.39
(tetrahydrobenzene) and 9.08 (CH-pyrimidine). In addition, the elemental analysis, revealed the
disappearance of the chloro substituent.
Reactions of 7 with different chloroacetyl derivates such as ethyl chloroacetate, chloroacetamide
or chloroacetonitrile afforded the corresponding selanyl derivatives 8-10. The IR spectra showed
the characteristic peaks at 1700 (C=O) for 8, 1670 (C=O) for 9 and 2217 (CN) cm–1 for 10. The
1H NMR spectra showed a triplet for the methyl group and quartet peaks for the methylene group
of 8, and the characteristic peaks at 6.56 (NH2-group), 2.71 (CH2-group) for 9 and 2.51 (CH2-
group) for 10 (Scheme 2).
Hydrazinolysis of ethyl (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetate
3
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(8) with hydrazine hydrate gave (5,6,7,8-Tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-
ylselanyl) acetohydrazide (11). Spectroscopic tools and elemental analysis confirmed the
structure of the hydrazide 11. The broad utility of heterocyclic hydrazine as precursors for the
synthesis of several condensed systems containing pyrazole derivatives (12-15a,b) has received
increasing attention. It was of interest to examine the chemistry and reactivity of the hydrazide
11 as a key intermediate. Condensation of 11 with ethyl acetoacetate and acetyl acetone in the
presence of sodium ethoxide under ring closure gave the cyclization products 5-methyl-2-[2-
(5,6,7,8-tetrahydro-1-benzothieno [2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydro-pyrazol-3-
one 12 and 1-(3,5-dimethyl-pyrazol -1-yl)-2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-
4-ylselanyl)ethanone
13.
Reactions
of
11
with
diethyl
malonate
and
ethoxymethylenemalononitrile or ethyl 2-cyano-3-ethoxyacetate gave the corresponding 1-[2-
(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl]-4,5-
dihydropyrazolidine-3,5-dione (14) and 5-amino-1-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]
pyrimidin-4-ylselanyl)acetyl]-1H-pyrazol-4-substituted (15a,b) respectively. (Scheme 3).
The structure of these compounds (12-15a,b) was confirmed by elemental analyses, IR, 1H NMR
and 13C NMR spectra. The data of all new compounds data are given in the Experimental.
CONCLUSION
Pyrazolobenzothienopyrimidine selanyl derivatives were synthesized. They represent a new
series of selenium containing heterocycles. The novel compounds are 5-methyl-2-[2-(5,6,7,8 -
tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazol-3-one, 1-(3,5-
dimethylpyrazol-1-yl)-2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)ethanone,
4
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1-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazol
idine-3,5-dione
and
4-substituted
5-amino-1-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-
d]pyrimidin -4-ylselanyl)acetyl]-1H-pyrazolcarbonitrile or -carboxylic acid ethyl ester.
EXPERIMENTAL
Melting points (uncorrected) were determined by using the Kofler melting point apparatus. IR
spectra (KBr, cm1) were recorded on a Pye–Unicam SP3-100 instrument at King Abdel-Aziz
1
University. H NMR spectra (400 MHz) were obtained on a Varian EM 390 USA instrument at
King Abdel-Aziz University. 13C NMR spectra (100 MHz) were recorded on a JNM-LA
spectrometer at King Abdel-Aziz University, Saudi Arabia. DMSO-d6 or CDCl3 were used as
solvents for both 1H and 13C-NMR spectroscopy. The spectra were internally referenced to TMS.
Peaks are reported in ppm downfield of TMS. Multiplicities are reported as singlet (s), doublet
(d), triplet (t) quartet (q). Mass spectra were recorded on a JEOL-JMS-AX 500 at Cairo national
research center, Cairo, Egypt. Elemental analyses were obtained on an Elementar Vario EL 1150
oC analyzer (Heraeus, Germany, Cairo University). Elemental analyses have been used to
determine the purity (> 95%) of the described compounds. Thin layer chromatography (TLC)
using silica gel plates checked the purity of the compounds. Column chromatography was carried
out on 0.04-0.063 mm (Merck) silica gel, TLC was carried out on aluminum backed silica plates
by Merck and plates were revealed using a UV 254 light.
Compounds 4 and 5 were prepared as previously described.38
4-Chloro-5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine (6).
A mixture of 5 (2. 06 g. 0.01 mol) was refluxed with PCl5 (2.51 g, 0. 012 mol) and POCl3 (5 mL)
5
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for 3h. After cooling, the mixture was carefully poured into over ice and ammonia solution in
small portions. The solid product was filtered off and recrystallized from benzene to give 6 as
1
pale brown crystals. Yield 75 %. Mp. 115-117 °C. IR:1600 (C=N). H NMR (CDCl3), δ: 1.94-
3.11 (m, 8H, tetrahydrobenzene), 8.73 (s, 1H, CH-pyrimidine). 13C NMR (CDCl3), δ: 168.8,
153.2, 151.4, 139.6, 128.8, 127.2, 121.5, 26.0, 23.5, 22.5. MS m/z (%): 224 [M+, 25%]. Anal.
Calcd. for C10H9ClN2S (224.71): C, 53.45; H, 4.04; Cl, 15.78; N, 12.47; S, 14.27 %. Found C,
53.55; H, 4.00; Cl, 15.45; N, 12.22; S, 14.11.
4,4'-Bis(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine)diselenide (7)
A mixture of 6 (2.24 g, 0.01 mol), selenium metal powder (0.79 g, 0.01 mol) and NaBH4 (0.74 g,
0.02 mol) in EtOH (30 mL) was stirred until colorless in an ice bath. After that, DMF (20 mL)
was added. The mixture became deep red brown and an additional amount of elemental selenium
(0.79 g, 0.01 mol) was added with ethanol (5 mL). The reaction mixture was refluxed for 3 h,
then cooled and poured into ice/HCl (200 g). The solid was filtered, dried and recrystallized from
1
ethanol. Yield 75%. Mp. 232-234 °C. IR: 1585 (C=N). H NMR (CDCl3), δ: 1.76-3.39 (m, 8H,
tetrahydrobenzene), 9.08 (s, 1H, CH-pyrimidine). 13C NMR (CDCl3), δ: 174.5, 166.9, 153.1,
148.5, 138.2, 133.7, 128.4, 24.5, 21.1, 17.1. MS, m/z (%): 535 [M+1, 5%]. Anal. Calcd. for
C20H18N4S2Se2 (536.43): C, 44.78; H, 3.38; N, 10.44; S, 11.95 %. Found C, 44.54; H, 3.35; N,
10.27; S, 11.88.
5,6,7,8-Tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl) derivatives 8,9 and 10
General procedures:
A small portion of NaBH4 was added to 7 (0.01 mol) in EtOH (20 mL). The reaction mixture
was stirred at room temperature until it was colorless. Then, ethyl chloroacetate, chloroacetamide
6
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or chloroacetonitrile (0.01 mol) was added. The reaction mixture was refluxed for 2 h and after
that poured onto crushed ice (200 g). Then, the solution was acidified with acetic acid. The
precipitated solid was filtered off and dried.
Ethyl (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetate (8);
1
Yield 65%. Mp. 220-222 °C. IR: 1700 (C=O), 1585 (C=N). H NMR (CDCl3), δ: 1.05-1.29 (t,
3H, CH2-CH3), 1.76-3.39 (m, 8H, tetrahydrobenzene), 3.1 (s, 2H, CH2), 4.13 (q, 2H, CH2-CH3),
9.08 (s, 1H, CH-pyrimidine). 13C NMR (CDCl3), δ: 174.5, 171.1, 166.9, 153.1, 148.5, 138.2,
133.7, 128.4, 65.4, 27.5, 24.5, 21.1, 17.1, 14.5. MS, m/z (%): 355 [M+, 10%]. Anal. Calcd. for
C14H16N2O2SSe (355.31): C, 47.32; H, 4.54; N, 7.88; S, 9.02 %. Found C, 47.14; H, 4.25; N,
7.77; S, 8.87.
(5,6,7,8-Tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetamide (9);
1
Yield 70%. Mp. 230-232 °C. IR: 1670 (C=O), 1585 (C=N). H NMR (CDCl3), δ: 6.56 (s, 2H,
NH2), 1.75-3.35 (m, 8H, tetrahydrobenzene), 2.71 (s, 2H, CH2), 9.08 (s, 1H, CH-pyrimidine). 13C
NMR (CDCl3), δ: 174.5, 171.1, 166.9, 153.1, 148.5, 138.2, 133.7, 128.4, 30.5, 24.5, 21.1, 17.1.
MS, m/z (%): 326 [M+, 5%]. Anal. Calcd. for C12H13N3OSSe (326.28): C, 44.17; H, 4.02; N,
12.88; S, 9.83 %. Found C, 44.10; H, 3.99; N, 12.57; S, 9.47.
(5,6,7,8-Tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)carbonitrile (10);
1
Yield 75%. Mp. 224-226 °C. IR: 2217 (CN), 1600 (C=N). H NMR (CDCl3), δ: 1.75-3.35 (m,
13
8H, tetrahydrobenzene), 2.51 (s, 2H, CH2), 9.50 (s, 1H, CH-pyrimidine). C NMR (CDCl3), δ:
166.9, 153.1, 148.5, 138.2, 133.7, 128.4, 115.5, 12.5, 24.5, 21.1, 17.1. MS, m/z (%): 308 [M+,
15%]. Anal. Calcd. for C12H11N3SSe (308.26): C, 46.76; H, 3.60; N, 13.63; S, 10.40 %. Found C,
46.70; H, 3.29; N, 13.50; S, 10.27.
7
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(5,6,7,8-Tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetohydrazide (11).
Compound 15 (3.55 g, 0.01 mol) was stirred in dioxan (10 mL) at room temperature. After that,
hydrazine hydrate (80%) (15 mL) was added. The reaction mixture was refluxed for 12 h. The
reaction mixture was poured onto crushed ice (100 g), the solid was filtered off, dried and
recrystallized from EtOH. Yield 75%. Mp. 242-244 °C. IR: 1660 (C=O), 3400, 3300, 3150
NHNH2), 1600 (C=N). 1H NMR (CDCl3), δ: 6.50 (s, 2H, NH2), 1.75-3.35 (m, 8H,
tetrahydrobenzene), 2.71 (s, 2H, CH2), 12.02 (s, 1H, NH), 9.20 (s, 1H, CH-pyrimidine). 13C
NMR (CDCl3), δ: 174.5, 170.5, 171.1, 166.9, 153.1, 148.5, 138.2, 133.7, 128.4, 29.5, 24.5, 21.1.
MS, m/z (%): 342 [M++1, 7%]. Anal. Calcd. for C12H14N4OSSe (341.29): C, 42.23; H, 4.13; N,
16.42; S, 9.40 %. Found C, 42.10; H, 3.95; N, 16.27; S, 9.27.
5-Methyl-2-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl)-2,4-
dihydro-pyrazol-3-one (12)
Compound 11 (3.41 g, 0.01 mol) was dissolved in ethanol (10 mL). Ethyl acetoacetate (1 mL)
and a few drops of NaOEt in EtOH were added. The reaction mixture was refluxed for 5 h. After
cooling, the reaction mixture was poured onto crushed ice (100 g), the solid was filtered off,
dried and recrystallized from ethanol; Yield 50%. Mp. 248-250 °C. IR: 1660 (C=O), 1670 (C=O),
1
1600 (C=N). H NMR (CDCl3), δ: 1.75-3.35 (m, 8H, tetrahydrobenzene), 2.45, 2.71 (s, 4H,
2CH2), 2.49 (s, 3H, CH3). 9.50 (s, 1H, CH-pyrimidine). 13C NMR (CDCl3), δ: 174.5, 171.1,
166.9, 152.6, 153.1, 148.5, 141.1, 138.2, 133.7, 110.9, 128.4, 30.5, 24.5, 21.1, 13.5, 14.0. MS,
m/z (%): 407 [M+, 5%]. Anal. Calcd. for C16H16N4O2SSe (407.35): C, 47.18; H, 3.96; N, 13.75; S,
7.87 %. Found C, 47.00; H, 3.59; N, 13.50; S, 7.49.
1-(3,5-Dimethyl-pyrazol-1-yl)-2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)
8
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ethanone (13).
Compound 11 (3.41 g, 0.01 mol) was dissolved in ethanol (10 mL). Acetylacetone (1 mL) and
NaOEt was added drop wise. The reaction mixture was refluxed for 5 h. The mixture was poured
onto crushed ice (100 g). The solid was filtered off, dried and recrystallized from ethanol; Yield
1
45%. Mp. 250-252 °C. IR: 1670 (C=O), 1610 (C=N). H NMR (CDCl3), δ: 7.38 (s, 1H, CH-
pyrazol), 1.75-3.35 (m, 8H, tetrahydrobenzene), 2.71 (s, 2H, CH2), 2.54-2.48 (m, 6H, 2CH3).
9.50 (s, 1H, CH-pyrimidine). 13C NMR (CDCl3), δ: 174.5, 171.1, 166.9, 153.1, 152.6, 148.5,
141.1, 138.2, 133.7, 110.9, 128.4, 32.5, 30.5, 24.5, 21.1, 13.5, 14.0. MS, m/z (%): 405 [M+, 10%].
Anal. Calcd. for C17H18N4OSSe (405.38): C, 50.37; H, 4.48; N, 13.82; S, 7.91 %. Found C,
50.17; H, 4.39; N, 13.58; S, 7.69.
1-[2-(5,6,7,8-Tetrahydro-1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl]-4,5-dihydro-
pyrazol idine-3,5-dione (14)
Compound 11 (3.41 g, 0.01 mol) and diethyl malonate (1.52 mL) in AcOH (50 mL) were
refluxed for 5 h. After cooling, the reaction mixture was poured onto crushed ice (100 g). The
solid was filtered off, dried and recrystallized from EtOH; Yield 55%. Mp. 240-242 °C. IR: 3150
1
(NH), 1660 (C=O), 1665 (C=O), 1670 (C=O), 1600 (C=N). H NMR (CDCl3), δ: 1.75-3.35 (m,
8H, tetrahydrobenzene), 2.40, 3.70 (s, 4H, 2CH2), 8.10 (s, 1H, NH), 9.50 (s, 1H, CH-pyrimidine).
13C NMR (CDCl3), δ: 172.5, 171.1, 168.1, 166.9, 152.6, 153.1, 148.5, 141.1, 138.2, 133.7, 128.4,
110.9, 46.5, 27.8. MS, m/z (%): 409 [M+, 8%]. Anal. Calcd. for C15H14N4O3SSe (409.32): C,
44.01; H, 3.45; N, 13.69; S, 7.83 %. Found C, 43.95; H, 3.39; N, 13.55; S, 7.69.
4-Substituted
5-amino-1-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-
ylselanyl)acetyl] -1H-pyrazolcarbonitrile or carboxylic acid ethyl ester (15a,b).
9
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General procedures
Compound 11 (3.41 g, 0.01 mol) in AcOH (50 mL) and ethoxymethylenemalononitrile or ethyl
2-cyano-3-ethoxyacetate (0.01 mol) were refluxed for 3 h. The reaction mixture was poured onto
crushed ice (100 g ), the solid was filtered off, dried and recrystallized from EtOH.
1
15a; Yield 42%. Mp. 260-262 °C. IR: 3350, 3150 (NH2), 2217(CN) 1670 (C=O). H NMR
(CDCl3), δ: 7.38 (s, 1H, CH-pyrazol), 6.50 (s, 2H, NH2) 1.75-3.35 (m, 8H, tetrahydrobenzene),
2.70 (s, 2H, CH2), 9.50 (s, 1H, CH-pyrimidine). 13C NMR (CDCl3), δ: 174.5, 171.1, 166.9, 153.1,
152.6, 148.5, 141.1, 138.2, 133.7, 110.9, 128.4, 30.5, 24.5, 32.5, 21.1, 13.5. MS, m/z (%): 417
[M+, 10 %]. Anal. Calcd. for C16H14N6OSSe (417.35): C, 46.05; H, 3.83; N, 20.14; S, 7.68 %.
Found C, 45.88; H, 3.79; N, 20.00; S, 7.60.
1
15b; Yield 45%. Mp. 200-202 °C. IR: 3350, 3150 (NH2), 1700 (C=O), 1670 (C=O). H NMR
(CDCl3), δ: 7.88 (s, 1H, CH-pyrazol), 1.75-3.45 (m, 8H, tetrahydrobenzene), 2.70 (s, 2H, CH2),
4.30 (q, 2H, CH2), 6.50 (s, 2H, NH2), 1.79 (t, 3H, CH3). 9.50 (s, 1H, CH-pyrimidine). 13C NMR
(CDCl3), δ: 174.5, 171.1, 166.9, 153.1, 152.6, 148.5, 141.1, 138.2, 133.7, 110.9, 106.1, 128.4,
61.5, 32.5, 30.5, 24.5, 23.1, 14.0. MS m/z (%): 464 [M+, 8%]. Anal. Calcd. for C18H19N5O3SSe
(464.40): C, 46.55; H, 4.12; N, 15.08; S, 6.90 %. Found C, 46.37; H, 4.00; N, 15.00; S, 6.79.
Acknowledgements
The authors thank the Taif University for support and encouragement to perform this work.
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Scheme 1. Synthesis of 4,4'-bis(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine) diselenide 7
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Scheme 2. Synthesis of benzothienopyrimidine selanyl derivatives
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Scheme 3. Synthesis of pyrazolbenzothienopyrimidine selanyl derivatives
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