Abstract
New pyrazolothienopyrimidines were synthesized. The key intermediate 4-aminothieno[2,3-c]pyrazole-5-carbonitrile 1 was converted to the chloroacetyl amino derivative 2 followed by nucleophilic substitution and Dimorth rearrangement upon treatment with nitrogen nucleophiles to give the pyrimidinones 3a-c. Treatment of 3a with formaldehyde and with triethyl orthoformate afforded the respective tetracyclic derivatives 4 and 5. Condensation of the amino group in the o-aminocarbonitrile 1 with triethyl orthoformate followed by cycloaddition reaction with hydrazine led to the formation of pyrazolothienopyrimidine 8. Compound 8 was used as a synthetic precursor to heterocyclic compounds comprised of pyrazole, triazole, triazine, and triazepine derivatives.
Introduction
Pyrazoles and their derivatives are an important class of heterocyclic compounds that exhibit a broad spectrum of biological activities [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22]. Many thienopyrazoles [23, 24, 25, 26, 27] and thienopyrimidines [38, 39] also exhibit exceptional bioactivity [23, 24, 25, 26, 27]. In continuation of our work on synthesis of new bioactive compounds containing thienopyrazole moiety [40, 41, 42, 43, 44], several thienopyrazolopyrimidine derivatives not known previously were synthesized.
Results and Discussion
The synthetic work was initiated by chloroacetylation reaction of 4-amino-3-methyl-1-phenyl-1H-thieno[2,3-c] pyrazole-5-carbonitrile (1), which afforded the chloroacetamido derivative 2 (Scheme 1). Reaction of 2 with various primary aromatic amines furnished the unexpected pyrimidinones 3a-c in good yields. This reaction apparently proceeds by nucleophilic substitution of the chloride ion with the primary amino group followed by Dimorth rearrangement in the presence of excess of the amine [45]. IR spectrum of 3a reveals disappearance of absorption band for the CN group present in compound 2 and appearance of absorption bands at 3440 and 3188 cm-1 that are characteristic for NH groups and absorption band at 1660 cm-1 for the amidic CONH group of pyrimidine. 1H NMR spectrum shows singlets at δ 6.10 and 12.68 attributed to exchangeable NHPh and NH pyrimidine groups.
Scheme 1
Treatment of the 5-(phenylaminomethyl)pyrimidinone 3a with formaldehyde in dioxane (Scheme 2) and the reaction with triethyl orthoformate afforded the respective tetracyclic pyrimidinones 4 and 5. Moreover, chlorination of the pyrimidinone 3a with phosphorus oxychloride furnished the chloropyrimidine 6. Both elemental and spectral analyses of compound 4- 6 fully support the assigned structures.
Scheme 2
Condensation of o-aminocarbonitrile 1 with triethyl orthoformate in the presence of a catalytic amount of acetic anhydride produced compound 7 (Scheme 3). Stirring of 7 with an equivalent amount of hydrazine hydrate yielded iminopyrimidine derivative 8. This transformation is characterized by disappearance of absorption band at 2199 cm-1 for CN group in compound 7 and appearance of absorption bands at 3439, 3286 and 3131 cm-1 due to NH and NH2 groups in product 8. 1H NMR spectra show disappearance of triplet and quartet signals for the ethyl group in compound 7 and appearance of singlet signals at δ 5.80 and 8.19 characteristic of NH2 and NH groups, respectively. Condensation of the amino-imino compound 8 with triethyl orthoformate produced the corresponding triazolopyrimidine 9 in an excellent yield, and dihydropyrazolopyrimidine 10 was obtained in low yield upon treatment of 8 with benzaldehyde.
Scheme 3
An additional series of novel tetracyclic pyrimidines 11-14 were synthesized by condensation of the aminoimino derivative 8 with different 1,3-dicarbonyl compounds (Scheme 3 and 4). Thus, condensation of compound 8 with diethyl malonate afforded the ethyl triazolopyrimidinyl acetate 11, while condensation with acetyl acetone produced triazolopyrimidine 12 instead of the expected diazepine product. Assignments of compounds 9-12 were elucidated by analysis of TLC, FT-IR, 1H NMR and 13C NMR data. IR spectrum of 11 lacks absorption bands of NH2 and NH groups and shows a sharp absorption band at 1740 cm-1 due to the ester. 1H NMR spectrum exhibits triplet and quartet signals at δ 1.25 and 4.20 with a J value of 7 Hz attributed to the ethyl ester group. 13C NMR shows signals at δ 14.5 and 61.4 for the ethyl group, in addition to the signal at 168.9 ppm for the ester carbonyl carbon as shown in Scheme 3.
Apparently, the mechanism of condensation of compound 8 with acetylacetone proceeds via cyclization of the imine with a retro-aldol type elimination of acetone. In a similar manner, condensation of 8 with ethyl acetoacetate and ethyl benzoylacetate afforded the corresponding triazepinones 13 and 14 (Scheme 4). Surprisingly, the treatment of 8 with phenacyl bromide in refluxing ethanol in the presence of triethylamine yielded the 3,8-diphenyltriazine 15 rather than its 2,8-diphenyl isomer. Formation of 15 can be explained by condensation between NH2 of the amino-imino 8 and carbonyl group of phenacyl bromide. The structure of compound 15 was confirmed on the basis of IR and 1H NMR spectra.
Scheme 4
Fusion of compound 8 with diethyl oxalate in the presence of acetic acid produced the corresponding triazinedione 17 in good yield. Triazolethione 18 was obtained upon heating of 8 with carbon disulfide in pyridine at 100oC. Both elemental and spectral analyses of the newly synthesized compounds 13-18 are in a full agreement with the postulated structures (Scheme 4).
Conclusions
Convenient and efficient methods for synthesis of novel pyrazolothienopyrimidines 3, 6 and 8 were described. These products were used as versatile starting materials for synthesis of new heterocyclic ring systems with imidazole, triazole, triazine and triazepine rings fused to a pyrazolothienopyrimidine moiety.
Experimental
All melting points are uncorrected. Elemental analyses were carried out at the Micro Analytical Center of Chemistry Department, Assiut University. The analysis for chlorine in compounds 2 and 6 was carried out by titration of chloride ion with mercuric nitrate solutions using a diphenylcarbazide indicator as reported [46, 47]. The FT-IR spectra were recorded using potassium bromide disks on a FT-IR 8201 PC Shimadzu instrument. 1H NMR (300 MHz) and 13C NMR (75MHz) spectra were obtained on a Bruker spectrometer in CDCl3 and DMSO-d6 using Me4Si as internal standard. All reactions were monitored by thin layer chromatography (TLC) on silica gel coated aluminum sheets. Compound 1 was synthesized according to the literature procedure [40, 41], mp 198-200oC.
2-Chloro-N-(5-cyano-3-methyl-1-phenyl-1H-thieno[2,3-c] pyrazol-4-yl)acetamide (2)
To a solution of o-amino-carbonitrile 1 (1.60 g, 6.29 mmol) in dioxane (25 mL), chloroacetyl chloride (0.80 mL, 10.0 mmol) was added, and the mixture was heated at 60-70oC for 2 h. After cooling and addition of diluted sodium carbonate solution, the resultant precipitate was filtered, dried and crystallized from ethanol: pale yellow crystals; yield 1.50 g (72%); mp > 360 oC; IR: ν 3360, 2185, 1655 cm-1; 1H NMR (DMSO-d6): δ 2.61 (s, 3H, CH3), 4.64 (s, 2H), 7.58-7.76 (m, 5H) and 8.96 (s, 1H). Anal. Calcd for C15H11ClN4OS (330.79): C, 54.46; H, 3.35; Cl, 10.72; N, 16.94; S, 9.69. Found: C, 54.56; H, 3.41; Cl, 10.77; N, 16.86; S, 9.63.
3-Methyl-1-phenyl-5((alkylarylamino)methyl)-1H-pyrazolo[4’,3’:4,5]thieno[3,2-d] pyrimidin-7(6H)-ones 3a-c
A mixture of chloroacetamide 2 (0.50 g, 1.5 mmol) and the corresponding amine (2 mmol) was gently heated without solvent for 10 min and then treated with ethanol (10 mL). The mixture was heated under reflux for 3 h. The resultant precipitate was filtered off, dried and crystallized from the proper solvent.
4.2.1. 3-Methyl-1-phenyl-5((phenylamino)methyl)-1H-pyrazolo[4’,3’:4,5]thieno[3,2-d]pyrimidin-7(6H)-one (3a)
Obtained by the reaction with aniline; crystallized from dioxane as yellow needles; yield 0.47 g (80%); mp 250-252oC; IR: ν 3440, 3188 (NH), 1660 (CO) cm-1; 1H NMR (DMSO-d6): δ 2.60 (s, 3H), 4.34 (s, 2H), 6.10 (s, 1H), 6.58-7.77 (m, 10H) and 12.68 (s, 1H); 13C NMR (DMSO-d6): δ 13.2, 53.5, 107.3, 113.2, 117.3, 117.6, 118.0, 125.6, 126.7, 129.4, 130.5, 138.9, 143.0, 144.8, 148.3, 158.6, 160.0. Anal. Calcd for C21H17N5OS (387.46): C, 65.10; H, 4.42; N, 18.08; S, 8.27. Found: C, 65.22; H, 4.53; N, 17.96; S, 8.42.
3-Methyl-1-phenyl-5-[(p-tolylamino)methyl]-1H-pyrazolo[4’,3’:4,5]thieno[3,2-d] pyrimidin-7(6H)-one (3b)
Obtained by the reaction with p-toluidine; crystallized from dioxane as brown crystals; yield 0.30 g (50%); mp 220-222oC; IR: ν 3423, 3370, 1664 cm-1; 1H NMR (DMSO-d6): δ 2.18 (s, 3H), 2.22 (s, 3H), 3.50 (s, 2H), 6.32 (s, 1H), 6.58-7.72 (m, 9H), 12.74 (s, 1H). Anal. Calcd for C22H19N5OS (401.13): C, 65.82; H, 4.77; N, 17.44; S, 7.99. Found: C, 65.73; H, 4.83; N, 17.43; S, 7.88.
5-{[(4-Methoxyphenyl)amino]methyl}-3-methyl-1-phenyl-1H-pyrazolo[4’,3’:4,5] thieno[3,2-d]pyrimidin-7(6H)-one (3c)
Obtained by the reaction with p- anisidine; crystallized from ethanol as brown crystals; yield 0.40 g (64%); mp 230-232oC; IR: ν 3425, 3210, 1676 cm-1; 1H NMR (DMSO-d6): δ 2.60 (s, 3H), 3.61 (s, 3H, CH3), 4.27 (s, 2H), 5.70 (s, 1H), 6.63-7.75 (m, 9H) and 12.69 (s, 1H). Anal. Calcd for C22H19N5O2S (417.49): C, 63.29; H, 4.59; N, 16.78; S, 7.68. Found: C, 63.33; H, 4.43; N, 16.73; S, 7.58.
3-Methyl-1,6-diphenyl-6,7-dihydro-1H-imidazo[1,5-a] pyrazolo[4’,3’;4,5]thieno[3,2-d]pyrimidin-9(5H)-one (4)
Formaldehyde was added to a stirred solution of pyrimidinone 3a (3.00 g, 7.74 mmol) in dioxane (30 mL). Stirring of the mixture was continued for 2 h. The resultant solid product was filtered off, dried and crystallized from dioxane to afford white crystals; yield 2.23 g, (72%); mp >300oC; IR: ν 1675 cm-1; 1H NMR: (CDCl3): δ 2.54 (s, 3H), 5.35 (s, 2H), 7.00 (s, 2H) and 7.33-7.70 (m, 10H); 13C NMR (CDCl3): δ 13.6, 66.5, 78.1, 105.3, 111.4, 117.2, 121.1, 124.6, 126.1, 128.4, 129.6, 135.3, 141.4, 145.5, 148.3, 152.6, 158.7, 168.5. Anal. Calcd for C22H17N5OS (399.47): C, 66.15; H, 4.29; N, 17.53; S, 8.03. Found: C, 66.18; H, 4.24; N, 17.42; S, 8.13.
7-Ethoxy-3-methyl-1,6-diphenyl-6,7-dihydro-1H-imidazo[1,5-a]pyrazolo[4’,3’;4,5] thieno[3,2-d]pyrimidine-9(5H)-one (5)
A mixture of pyrimidinone 3a (3.00 g, 7.74 mmol), triethyl orthoformate (1.30 mL, 7.82 mmol) and a catalytic amount of acetic acid (0.25 mL) was heated under reflux for 1 h. The resultant solid product was filtered off, dried and crystallized from ethanol as brown crystals; yield 2.23 g (65%); mp 298-300oC; IR: ν 1670 cm-1; 1H NMR (CDCl3): δ 1.48 (t, J = 7 Hz, 3H), 2.54 (s, 3H), 4.50 (q, J = 7 Hz, 2H), 5.00 (s, 2H), 6.71 (s, 1H), 7.33-8.10 (m, 10H); 13C NMR (CDCl3): δ 13.0, 57.4, 60.6, 109.5, 109.7, 113.6, 117.4, 118.0, 123.9, 126.7, 129.7, 130.4, 141.8, 157.4, 158.1, 158.6, 159.1, 159.6, 169.5. Anal. Calcd for C24H21N5O2S (443.53): C, 64.99; H, 4.77; N, 15.79; S, 7.23. Found: C, 64.88; H, 4.74; N, 15.72; S, 7.13.
N-[(7-Chloro-3-methyl-1-phenyl-1H-pyrazolo[4’,3’;4,5] thieno[3,2-d]pyrimidine-5-yl) methyl]aniline (6)
A solution of pyrimidinone 3a (3.00 g, 7.74 mmol) in phosphorus oxychloride (30 mL) was heated under reflux for 2 h, then cooled and poured into an ice-water. The precipitate was filtered off, dried and crystallized from ethanol to give pale yellow crystals; yield 2.20 g (70%); mp 288-290oC; IR: ν 3380 (NH) cm-1; 1H NMR (CDCl3): δ 2.81 (s, 3H), 4.73 (s, 2H), 6.90-7.80 (m, 10H) and 8.58 (s, 1H). Anal. Calcd for C21H16ClN5S (405.90): C, 62.14; H, 3.97; Cl, 8.73; N, 17.25; S, 7.90. Found: C, 62.18; H, 3.84; Cl, 8.70; N, 17.32; S, 7.83.
Ethyl N-(5-cyano-3-methyl-1-phenyl-1H-thieno[2,3-c] pyrazol-4-yl)formimidate (7)
A mixture of o-amino-carbonitrile 1 (3.00 g, 11.8 mmol), and triethyl orthoformate (6.00 mL, 36.1 mmol) in acetic acid (30 mL) was heated under reflux for 2 h. The resultant solid product was collected, dried and crystallized from ethanol as brown crystals; yield 2.89 g (79%); mp 80-82oC; IR: ν 2199 (CN) cm-1; 1H NMR (CDCl3): δ 1.50 (t, J = 7 Hz, 3H), 2.54 (s, 3H), 4.46 (q, J = 7 Hz, 2H), 7.33-7.70 (m, 5H) and 8.10 (s, 1H). Anal. Calcd for C16H14N4OS (310.38): C, 61.92; H, 4.55; N, 18.05; S, 10.33. Found: C, 61.88; H, 4.64; N, 18.12; S, 10.28.
6-Amino-7-imino-3-methyl-1-phenyl-1,7-dihydro-6H-pyrazolo[4’,3’:4,5]thieno[3,2-d] pyrimidine (8)
To a stirred solution of the formimidate 7 (2.96 g, 9.54 mmol) in warm dioxane (30 mL), hydrazine hydrate (0.80 mL, 16 mmol) was added dropwise during 5 min. Stirring of the mixture was continued for an additional 1h. The solid precipitate was filtered off, dried and crystallized from ethanol as white crystals; yield 2.40 g (85%); mp 220-222oC; IR: ν 3439, 3286, 3131 cm-1; 1H NMR (DMSO-d6): δ 2.57 (s, 3H), 5.80 (s, 2H), 7.00 (s, 1H), 7.33-7.76 (m, 5H) and 8.19 (s, 1H). Anal. Calcd for C14H12N6S (296.35): C, 56.74; H, 4.08; N, 28.36; S, 10.82. Found: C, 56.70; H, 4.22; N, 28.42; S, 10.76.
7-Methyl-9-phenyl-9H-pyrazolo[4’,3’:4,5]thieno[2,3-e] [1,2,4]triazolo[1,5-c]pyrimidine (9)
A mixture of the aminoiminopyrimidine 8 (0.70 g, 2.4 mmol) and triethyl orthoformate (5.00 mL, 30.1 mmol) and a catalytic amount of acetic acid (0.30 mL) was heated under reflux for 3 h at 120oC. The separated solid product was filtered off, dried and crystallized from dioxane as white crystals; yield 0.67 g (92%); mp 266-268oC; IR: ν 1595 cm-1; 1H NMR (DMSO-d6): δ 2.74 (s, 3H), 7.40-7.85 (m, 5H), 8.75 (s, 1H) and 9.91 (s, 1H). Anal. Calcd for C15H10N6S (306.35): C, 58.81; H, 3.29; N, 27.43; S, 10.47. Found: C, 58.70; H, 3.32; N, 27.52; S, 10.55.
7-Methyl-2,9-diphenyl-2,9-dihydro-9H-pyrazolo[4’,3’:4,5] thieno[2,3-e][1,2,4]triazolo [1,5-c]pyrimidine (10)
A solution of pyrimidine 8 (0.70 g, 2.4 mmol), benzaldehyde (2.10 mL, 20.6 mmol) and a catalytic amount of piperidine (0.25 mL) was heated at 180oC for 10 min, then cooled, treated with absolute ethanol (20 mL) and heated under reflux for an additional 2h. The solid precipitate was filtered off and crystallized from acetic acid as white crystals; yield 0.29 g (38%); mp 300-302oC; IR: ν 3302 cm-1; 1H NMR (DMSO-d6): δ 2.67 (s, 3H), 4.13 (s, 1H), 5.24 (s, 1H), 7.38-7.86 (m, 10H) and 8.63 (s, 1H); 13C NMR (DMSO-d6): δ 13.3, 85.9, 108.8, 119.7, 124.1, 125.7, 127.1, 128.9, 130.7, 131.4, 134.2, 138.1, 140.3, 141.3, 143.4, 146.9, 160.3. Anal. Calcd for C21H16N6S (384.12): C, 65.61; H, 4.19; N, 21.86; S, 8.34. Found: C, 65.76; H, 4.25; N, 21.92; S, 8.33.
Ethyl (7-methyl-9-phenyl-9H-pyrazolo[4’,3’:4,5] thieno[2,3-e] [1,2,4]triazolo[1,5-c] pyrimidine)-2-ylacetate (11)
A mixture of pyrimidine 8 (0.70 g, 2.4 mmol) and diethyl malonate (5.00 mL, 32.8 mmol) was heated for 10 min, then treated with ethanol (20 mL) and heated under reflux for an additional 2h. The solid product that formed on cooling was collected, dried and crystallized from ethanol as pale brown crystals; yield 0.45 g (49%); mp 100-102oC; IR: ν 1740 cm-1; 1H NMR (DMSO-d6): δ 1.25 (t, J = 7 Hz, 3H), 2.69 (s, 3H), 4.10 (s, 2H), 4.20 (q, J = 7 Hz, 2H), 7.40-7.78 (m, 5H) and 9.80 (s, 1H); 13C NMR (DMSO-d6): δ 13.2, 14.5, 35.1, 61.4, 116.8, 117.0, 124.9, 126.7, 130.4, 138.5, 140.9, 141.5, 144.0, 148.7, 165.8, 168.9; Anal. Calcd for C19H16N6O2S (392.44): C, 58.15; H, 4.11; N, 21.42; S, 8.17. Found: C, 58.20; H, 4.07; N, 21.36; S, 8.27.
2,7-Dimethyl-9-phenyl-9H-pyrazolo[4’,3’:4,5]thieno[2,3-e][1,2,4]triazolo[1,5-c] pyrimidine (12)
A mixture of pyrimidine 8 (0.70 g, 2.4 mmol) and acetylacetone (3.00 mL, 29.4 mmol) was gently heated for 15 min, then treated with ethanol (20 mL) and heated under reflux for an additional 3h. The solid product formed after cooling was filtered off and crystallized from dioxane as brown crystals; yield 0.38 g (50%); mp 180-182oC; IR: ν 1598 cm-1; 1H NMR (DMSO-d6): δ 2.57 (s, 3H), 2.99 (s, 3H), 7.40-7.85 (m, 5H) and 9.92 (s, 1H); MS (EI, 70 eV): m/z 320 (M+, 100%). Anal. Calcd for C16H12N6S (320.37): C, 59.98; H, 3.78; N, 26.23; S, 10.01. Found: C, 59.95; H, 3.74; N, 26.11; S, 10.11.
4,9-Dimethyl-11-phenyl-11H-pyrazolo[4’’,3’’;4’,5’] thieno [3’,2’;4,5]pyrimido[1,6-b] [1,2,4]triazepin-2(3H)-one (13)
A mixture of pyrimidine 8 (0.70 g, 2.4 mmol) and ethyl acetoacetate (2.00 mL, 15.7 mmol) was gently heated for 15 min, then treated with ethanol (20 mL) and heated under reflux for an additional 2h. The solid product which separated out during reflux was collected, dried and crystallized from ethanol as brown crystals; yield 0.63 g (86 %); mp 200-202oC; IR: ν 1715 cm-1; 1H NMR (DMSO-d6): δ 2.28 (s, 3H), 2.70 (s, 3H), 4.16 (s, 2H), 7.39-7.85 (m, 5H), 9.80 (s, 1H). Anal. Calcd for C18H14N6OS (362.41): C, 59.66; H, 3.89; N, 23.19; S, 8.85. Found: C, 59.55; H, 3.75; N, 23.22; S, 8.77.
9-Methyl-2,11-diphenyl-11H-pyrazolo[4”,3”;4’,5’]thieno [3’,2’;4,5]pyrimido[1,6-b][1,2,4]triazepin-4(5H)-one (14)
A solution of pyrimidine 8 (0.74 g, 2.5 mmol), ethyl benzoylacetate (2.00 mL, 11.5 mmol) and a catalytic amount of piperidine (0.25 mL) was gently heated for 15 min, then treated with ethanol (20 mL) and heated under reflux for an additional 2h. The solid product that formed during reflux was filtered off and crystallized from ethanol as brown crystals; yield 0.36 g (42%); mp 188-190oC; IR: ν 3462 (NH), 1685 cm-1; 1H NMR (DMSO-d6): δ 2.71 (s, 3H), 4.80 (s, 1H), 7.41 (s, 1H), 7.56-8.13 (m, 10H) and 9.82 (s, 1H); 13C NMR (DMSO-d6): δ 13.3, 98.3, 103.7, 110.2, 117.9, 126.8, 129.1, 129.3, 130.5, 134.1, 136.4, 137.2, 141.0, 145.0, 152.5, 160.1, 162.3, 167.5, 170.7; MS (EI, 70eV) m/z 424 (M+, 100%). Anal. Calcd for C23H16N6OS (424.48): C, 65.08; H, 3.80; N, 19.80; S, 7.55. Found: C, 65.20; H, 4.00; N, 19.62; S, 7.37.
8-Methyl-3,10-diphenyl-2,10-dihydropyrazolo[4’’,3’’:4’,5’] thieno[3’,2’:4,5]pyrimido [1,6-b][1,2,4] triazine (15)
A mixture of compound 8 (0.74 g, 2.5 mmol), phenacyl bromide (0.50 g, 2.5 mmol) and triethylamine (0.30 mL) in ethanol (20 mL) was heated under reflux for 3h. The solid product that formed on cooling was filtered off, dried and crystallized from ethanol as white crystals; yield 0.59 g (74 %); mp 280-282oC; IR: ν 1597 cm-1; 1H NMR (CDCl3): δ 2.60 (s, 2H), 2.79 (s, 3H), 7.53-8.21 (m, 10H) and 8.64 (s, 1H). Anal. Calcd for C22H16N6S (396.47): C, 66.65; H, 4.07; N, 21.20; S, 8.09. Found: C, 66.58; H, 4.17; N, 21.22; S, 8.18.
8-Methyl-10-phenylpyrazolo[4’’,3’’;4’,5’]thieno [3’,2’:4,5]pyrimido[1,6-b][1,2,4] triazine-2,3(4H,10H)-dione (17)
A mixture of compound 8 (0.74 g, 2.5 mmol) and diethyl oxalate (0.40 mL, 2.9 mmol) in acetic acid (20 mL) was heated under reflux for 6 h. The solid product that formed on cooling was filtered off, dried and crystallized from ethanol as pale yellow crystals; yield 0.68 g (73%); mp 175-177oC; IR: ν 3375 (NH), 1700, 1661 cm-1; 1H NMR (DMSO-d6): δ 2.61 (s, 3H), 7.35-7.76 (m, 5H), 8.31 (s, 1H) and 12.83 (s, 1H); 13C NMR (DMSO-d6): δ 13.3, 107.5, 117.9, 121.2, 125.6, 126.7, 130.5, 138.9, 142.8, 144.7, 148.7, 157.9, 160.1, 170.2. Anal. Calcd for C16H10N6O2S (350.36): C, 54.85; H, 2.88; N, 23.99; S, 9.15. Found: C, 54.98; H, 2.95; N, 24.20; S, 9.05.
7-Methyl-9-phenyl-9H-pyrazolo[4’,3’:4,5]thieno [2,3-e][1,2,4]triazolo[1,5-c] pyrimidine-2(3H)-thione (18)
A solution of compound 8 (0.74 g, 2.5 mmol) and carbon disulfide (2.00 mL, 33.1 mmol) in pyridine (10 mL) was heated under reflux for 8h. The solid product that separated out during reflux was filtered off, dried and crystallized from ethanol as yellow crystals; yield 0.28 g, (35%); mp 286-288oC; IR: ν 3447, 1239 cm-1; 1H NMR (DMSO-d6): δ 2.73 (s, 3H), 7.44-7.84 (m, 5H), 8.44 (s, 1H) and 9.88 (s, 1H). Anal. Calcd for C15H10N6S2 (338.41): C, 53.24; H, 2.98; N, 24.83; S, 18.95. Found: C, 53.27; H, 2.94; N, 24.75; S, 18.83.
Acknowledgements
The authors are grateful to Professor Kamal I. Aly, Chairman of Chemistry Department, for providing the chemistry facilities.
References
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