untitled European Journal of Chemistry 2 (4) (2011) 509‐513 European Journal of Chemistry ISSN 2153‐2249 (Print) / ISSN 2153‐2257 (Online)  2011 EURJCHEM DOI:10.5155/eurjchem.2.4.509‐513.463 European Journal of Chemistry Journal homepage: www.eurjchem.com Synthesis of some new of thieno[2,3‐b]pyridines, pyrazolo[1,5‐a]pyrimidine, [1,2,4]triazolo[1,5‐a]pyrimidine, pyrazolo[5,1‐c]triazine and pyrimido[1,2‐a]benzimidazole derivatives containing pyridine moiety Mahmoud Abdallah Mohameda, Eman Kamal Ahmad Abdelallb, Yasser Hassan Zakic and Abdou Osman Abdelhamidd,* a Department of Textile, Faculty of Industrial Education, Beni‐Suef University, Beni‐Suef‐62514, Egypt b Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni‐Suef University, Beni‐Suef‐62514, Egypt c Department of Chemistry, Faculty of Science, Beni‐Suef University, Beni‐Suef‐62514, Egypt d Department of Chemistry, Faculty of Science, Cairo University, Giza‐12613, Egypt *Corresponding author at: Department of Chemistry, Faculty of Science, Cairo University, Giza‐12613, Egypt. Tel.: +202.35676573; fax: +202.35727556. E‐mail address: abdelhamid45@gmail.com (A.O. Abdelhamid). ARTICLE INFORMATION ABSTRACT Received: 18 May 2011 Received in revised form: 07 June 2011 Accepted: 16 June 2011 Online: 31 December 2011 KEYWORDS Pyrazolo[1,5‐a]pyrimidine, [1,2,4]triazolo[1,5‐a]pyrimidine and pyrimido[1,2‐a] benzimida‐ zole derivatives were synthesized by reaction of sodium salt of 3‐hydroxy‐(1‐pyridin‐2‐ yl)prop‐2‐en‐1‐one or sodium salt of 3‐hydroxy‐1‐(pyridin‐3‐yl)prop‐2‐en‐1‐one with different heterocyclic amines in piperidenium acetate. Also, 3‐amino‐6‐(2‐pyridyl)thieno[2,3‐ b]pyridine derivatives were synthesized via reaction of pyridine‐2‐thione with various halogenated compounds. The structures of the newly synthesized compounds were confirmed by elemental analysis, spectral data, X‐ray and alternative synthetic routes whenever possible. Pyridines Thieno[2,3‐b]pyridine Pyrazolo[1,5‐a]pyrimidine Triazolo[1,5‐a]pyrimidine Pyrimido[1,2‐a]benzimidazole Piperidenium acetate 1. Introduction Pyridine derivatives are widely applied in medicine and agriculture, for example, used as anticancer [1], anti‐hyper‐ tension [2] and antifungal [3], pesticides [4], herbicides [4], plant growth reagents [4] etc. Several thieno[2,3‐b]pyridine derivatives are known to possess antibacterial [5], antihyper‐ tensive [6] and gonadotropinreleasing hormone antagonizing [7,8] activity. Pyridothienopyrimidine derivatives have found applications as analgesics, antipyretics [9] and anti‐ inflammatories [10]. Moreover, some pyridothienotriazines are known to exhibit antianaphylactic [11] and antiallergic activity [12]. In view of these facts and as a continuation of our previous work [13,14‐19], we report herein the synthesis of new compounds bearing both pyridine, thienopyrimidine, pyrazolo[1,5‐a]pyrimidine, [1,2,4]triazolo[1,5‐a]pyrimidine and pyrimido[1,2‐a]benzimidazole with the objective of obtaining new biologically active compounds. 2. Experimental 2.1. Instrumentation All melting points were determined on an electrothermal apparatus and are uncorrected. IR spectra were recorded (KBr discs) on a Shimadzu FT‐IR 8201 PC spectrophotometer. 1H and 13C NMR spectra were recorded in CDCl3 and (CD3)2SO solutions on a Varian Gemini 300 MHz spectrometer and chemical shifts are expressed as δ ppm using TMS as an internal reference. Mass spectra were recorded on a GC‐MS QP 1000 EX Shimadzu. Elemental analyses were carried out at the Microanalytical Center of Cairo University. X‐ray single crystals analysis was obtained from the National Research Centre‐ Dokki, Cairo, Egypt. 2.2. Synthesis of sodium salt of 3‐hydroxy‐1‐(pyridin‐2‐ yl)prop‐2‐en‐1‐one (2) and sodium salt of 3‐hydroxy‐1‐ (pyridin‐3‐yl)prop‐2‐en‐1‐one (15) In a three‐necked flask (250 mL) sodium methoxide (0.054 g, 10 mmol) and ether (20 mL) were poured over through separating funnel the appropriate of 2‐acetylpyridine (1) or 3‐acetylpyridine (1.2 g, 10 mmol) with ethyl formate (0.74 g, 10 mmol) with efficient stirring. The solid product was collected and used directly in the reactions. 2.3. Synthesis of 2‐(2‐(3‐cyano‐6‐(pyridin‐2‐yl)pyridin‐2‐ yl)disulfanyl)‐6‐(pyridin‐2‐yl)pyridine‐3‐carbonitrile (3), 1,2‐dihydro‐2‐oxo‐6‐(pyridin‐3‐yl)pyridine‐3‐carbonitrile (16), 2‐mercapto‐6‐(pyridin‐3‐yl)pyridine‐3‐carbonitrile (17), pyrazolo[1,5‐a]pyrimidines (9, 12, 23, 24), [1,2,4]triazolo[1,5‐a]pyrimidines (13, 25), and hydropyrimidino[1,2‐a]benzimidazoles (14, 26) Method A: A solution of the appropriate of 2 or 6, (10 mmol), the appropriate cyanoacetamide, cynothioacetamide, 3‐amino‐4‐phenylepyrazole, 3‐amino‐4‐cyanopyrazole, 3‐amino‐1,2,4‐triazole, 2‐aminobenzimidazole (10 mmol) and 510 Mohamed et al. / European Journal of Chemistry 2 (4) (2011) 509‐513 piperidine acetate (1 mL) in water (3 mL) was refluxed for 10 minutes. Acetic acid (1.5 mL) was added to the hot solution. The solid product was filtered off and recrystallized from the proper solvent to give products 3, 9, 12‐14, 16, 17 and 23‐26 (Scheme 1‐4). Method B: An equimolar amount of 3‐dimethylamino‐1‐ pyridin‐2‐ylpropenone (11) (5 mmol), the appropriate 3‐amino‐4‐phenylpyrazole, 3‐amino‐4‐cyanopyrazole, 3‐amino‐1,2,4‐triazole, 2‐aminobenzimidazole, and ammonium acetate (5 mmol) in acetic acid (10 mL) was heated under reflux for 4 hrs. The resulting solid was collected and recrystal‐ lized from the proper solvent gave products 9, 13 and 14. Method C: An equimolar amount of N,N‐dimethyl‐N'‐(4‐ phenyl‐1H‐pyrazol‐5‐yl)formamidine (10) and appropriate 2‐acetylpyridine or 3‐acetylpyridine (5 mmol) in ethanol (10 mL) was heated under reflux for 3 hrs. The resulting solid was collected and recrystallized from the proper solvent gave products 9 and 23, respectively. 2‐(2‐(3‐cyano‐6‐(pyridin‐2‐yl)pyridin‐2‐yl)disulfanyl)‐6‐ (pyridin‐2‐yl)pyridine‐3‐carbonitrile (3): Pale yellow crystals from ethanol. Yield: 73%. M.p.: > 300 °C. FT‐IR (KBr, cm‐1): 3054 (CH, aromatic), 2219 (CN). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.44 (t, 2H), 7.48 (t, 2H), 8.05 (d, 2H), 8.45 (d, 4H), 8.66 (d, 2H). MS (m/z, %): 425 (0.6, M+1), 424 (1.7%, M), 215 (6.0%), 214 (16.5%), 213 (100%, 0.5), 212 (25.7%), 169 (49.2%), 79 (10%), 78 (33.5%). Anal. calcd. for C22H12N6S2 (424.51): C, 62.25; H, 2.85; N, 19.80; S, 15.11. Found: C, 62.32; H, 2.72; N, 19.70; S, 15.21%. 3‐Phenyl‐5‐(pyridin‐2‐yl)pyrazolo[1,5‐a]pyrimidine (9): Yellow crystals from EtOH. Yield: 70%. M.p.: 220‐222 °C. FT‐IR (KBr, cm‐1): 3043 (CH, aromatic), 1633 (C=N). 1H NMR (300 MHz, CDCl3, δ, ppm): 6.91 (d, 2H), 7.27 (d, 1H), 7.55‐7.75 (m, 5H), 8.15 (d, 1H), 8.72 (d, 1H), 8.92 (d, 2H). MS (m/z, %): 273 (1.8, M+1), 223 (10), 222 (15), 195 (10), 146 (15), 117 (26), 78 (100). Anal. calcd. for C17H12N4 (272.3): C, 74.98; H, 4.44; N, 20.58. Found: C, 75.18; H, 4.23; N, 20.62%. 5‐(Pyridin‐2‐yl)pyrazolo[1,5‐a]pyrimidine‐3‐carbonitrile (12): Yellow crystals from EtOH. Yield: 76%. M.p.: 215‐217 °C. FT‐IR (KBr, cm‐1): 3043 (CH, aromatic), 2219 (CN), 1623 (C=N). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.18 (t, 1H), 7.77 (d, 1H), 7.92 (t, 1H), 8.41 (d, 1H), 8.72 (d, 1H), 9.23 (s, 1H), 9.84 (d, 1H). Anal. calcd. for C12H7N5 (221.22): C, 65.15; H, 3.19; N, 31.66. Found: C, 65.25; H, 3.27; N, 31.78%. 5‐(Pyridin‐2‐yl)‐[1,2,4]triazolo[1,5‐a]pyrimidine (13): Light brown crystals from EtOH. Yield: 76%. M.p.: 225‐227 °C. FT‐IR (KBr, cm‐1): 3043 (CH, aromatic), 1618 (C=N). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.29 (t, 1H), 7.41 (d, 1H), 7.95 (t, 1H), 8.41 (s, 1H), 8.70 (d, 1H), 8.87 (d, 1H), 9.54 (d, 1H). Anal. calcd. for C10H7N5 (197.2): C, 60.91; H, 3.58; N, 35.51. Found: C, 61.11; H, 3.82; N, 35.71%. 2‐(2‐Pyridyl)‐4a‐hydropyrimidino[1,2‐a]benzimidazole (14): Yellow crystals from EtOH. Yield: 76%. M.p.: 230‐233 °C. FT‐IR (KBr, cm‐1): 3043 (CH, aromatic), 1624 (C=N). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.27 (t, 1H), 7.40‐7.58 (m, 2H), 7.91‐8.00 (d, 2H), 8.41 (d, 1H), 8.66 (d, 2H), 8.87 (d, 1H), 9.12 (d, 1H). Anal. calcd. for C15H10N4 (246.27): C, 73.16; H, 4.09; N, 22.75. Found: C, 73.26; H, 3.79; N, 22.58%. 1,2‐Dihydro‐2‐oxo‐6‐(pyridin‐3‐yl)pyridine‐3‐carbonitrile (16): Pale yellow crystals from DMF. Yield: 70%. M.p.: > 300 °C. FT‐IR (KBr, cm‐1): 3350 (NH), 3043 (CH, aromatic), 2210 (CN), 1680 (CO), 1622 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 6.88 (t, 1H), 7.53 (t, 1H), 8.25 (d, 1H), 8.69 (d, 1H), 8.70 (d, 1H), 8.99 (d, 1H), 9.05 (s, br., 1H, NH). Anal. calcd. for C11H7N3O (197.19): C, 67.00; H, 3.58; N, 21.31. Found: 67.14; H, 3.65; N, 21.11%. 2‐Mercapto‐6‐(pyridin‐3‐yl)pyridine‐3‐carbonitrile (17): Pale yellow crystals from ethanol. Yield: 73%. M.p.: 230‐232 °C. FT‐IR (KBr, cm‐1): 3013 (CH, aromatic), 2217 (CN). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.14 (t, 1H), 7.56 (t, 1H), 8.17 (d, 1H), 8.73 (d, 1H), 8.92 (d, 2H), 14.25 (s, br., 1H, SH). MS (m/z, %): 425 (0.6, M+1), 424 (1.7, M), 215 (6.0), 214 (16.5), 213 (100, 0.5), 212 (25.7), 169 (49.2), 79 (10%), 78 (33.5). Anal. calcd. for C11H7N3S (213.26): C, 61.95; H, 3.31; N, 19.70; S, 15.03. Found: C, 62.12; H, 3.22; N, 19.80; S, 15.11%. 3‐Phenyl‐5‐(pyridin‐3‐yl)pyrazolo[1,5‐a]pyrimidine (23): Yellow crystals from EtOH. Yield: 65%. M.p.: 120‐122 °C. FT‐IR (KBr, cm‐1): 3043 (CH, aromatic). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.09 (t, 2H), 7.47 (t, 1H), 7.77 (d, 2H), 7.90 (t, 1H), 8.15 (d, 1H), 8.41 (t, 2H), 8.73 (t, 2H), 9.12 (d, 1H). MS (m/z, %): 274 (2.19), 273 (18.5), 272 (100.0). Anal. calcd. for C17H12N4 (272.3): C, 74.98; H, 4.44; N, 20.58. Found: C, 74.78; H, 4.32; N, 20.42%. 5‐(Pyridin‐3‐yl)pyrazolo[1,5‐a]pyrimidine‐3‐carbonitrile (24): Colorless crystals from EtOH. Yield: 76%. M.p.: 240‐242 °C. FT‐IR (KBr, cm‐1): 3043, (CH, aromatic), 2219 (CN), 1628 (C=N). 1H NMR (300 MHz, CDCl3, δ, ppm): 6.98 (d, 1H), 7.27 (t, 1H), 7.48‐7.56 (m, 1H), 8.41 (d, 1H), 8.72 (d, 1H), 9.23 (s, 1H), 9.84 (d, 1H). MS (m/z, %): 221 (90, M+1), 194 (10), 168 (8.2), 142 (14), 88 (22.4), 87 (13.3), 66 (15.3), 53 (24.5), 52 (62), 51 (98). Anal. calcd. for C12H7N5 (221.22): C, 65.15; H, 3.19; N, 31.66. Found: C, 65.04; H, 3.35; N, 31.82%. 5‐(Pyridin‐3‐yl)‐[1,2,4]triazolo[1,5‐a]pyrimidine (25): Colorless crystals from EtOH. Yield: 76%. M.p.: 230‐233 °C. FT‐ IR (KBr, cm‐1): 3043 (CH, aromatic), 1622 (C=N). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.27 (t, 1H), 7.40 (d, 1H), 7.55 (s, 1H), 8.41 (s, 1H), 8.66‐8.75 (m, 1H), 9.12 (d, 1H), 9.27 (s, 1H). Anal. calcd. for C10H7N5 (197.2): C, 60.91; H, 3.58; N, 35.51. Found: C, 61.01; H, 3.62; N, 35.61%. 2‐(3‐Pyridyl)‐4a‐hydropyrimidino[1,2‐a]benzimidazole (26): Yellow crystals from EtOH. Yield: 76%. M.p.: 310‐312 °C. FT‐IR (KBr, cm‐1): 3043 (CH, aromatic), 1626 (C=N). 1H NMR (300 MHz, CDCl3, δ, ppm): 7.27 (t, 1H), 7.42‐7.58 (m, 2H), 7.91‐8.00 (d, 2H), 8.41 (d, 1H), 8.66 (d, 2H), 8.87 (d, 1H), 9.14 (d, 1H). Anal. calcd. for C15H10N4 (246.27): C, 73.16; H, 4.09; N, 22.75. Found: C, 73.05; H, 4.19; N, 22.89%. N CH3 O + HCO2C2H5 CH3ONa N O ONa 1 2 NCCH2C(S)NH2 3 N N S CO2C2H5 NH2 4 N N N S S N N N ClCH2COOC2H5 Scheme 1 2.4. Synthesis of ethyl 3‐amino‐6‐(2‐pyridyl)thieno[2,3‐ b]pyridine‐2‐carboxylate (4), ethyl 3‐amino‐6‐(3‐ pyridyl)thieno[2,3‐b]pyridine‐2‐carboxylate (18), 3‐amino‐ 6‐(3‐pyridyl)thieno[2,3‐b]pyridine‐2‐ylphenylketone (19), 3‐ amino‐6‐(3‐pyridyl)thieno[2,3‐b]pyridine‐2‐carbonitrile (20) and 2‐methylthio‐6‐(3‐pyridyl)pyridine‐3‐carbonitrile (21) A mixture of the appropriate 3 and 7 (2.13 g, 10 mmole) and potassium hydroxide (0.56 g, 10 mmole) in N,N‐ dimethylformamide (20 mL) was stirred for 2 hrs at room temperature. Each of ethyl chloroacetate, ω‐bromoaceto‐ phenonem, chloroacetonitrile and iodomethane (10 mmole each) was added and stirring was continued for 2 hrs. The resulting solid was collected and recrystallized from the proper solvent to give 4, 9‐12, respectively. Ethyl 3‐amino‐6‐(pyridin‐2‐yl)thieno[2,3‐b]pyridine‐ 2‐carboxylate (4): Pale yellow crystals from Dioxane. Yield: 85%. M.p.: 277‐280 °C. FT‐IR (KBr, cm‐1): 3280, 3204 (NH2), 3077 (CH, Aromatic), 1715 (CO), 1617 (C=N). Mohamed et al. / European Journal of Chemistry 2 (4) (2011) 509‐513 511 N O ONa + N H N NH2 Ph N O ONa N N N Ph N N O ONa N N N NH HN N Ph Ph NN CH3 O + HN N H2N Ph N O N CH3 CH3 2 5 6 8 7 9 5 101 11 N H N N Ph N CH3 H3C Scheme 2 Scheme 3 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 1.27 (t, 3H, CH2CH3), 4.23 (q, 2H, CH2CH3), 6.82 (s, br, 2H, NH2), 7.30 (t, 1H), 7.96 (d, 1H), 8.02 (t, 1H), 8.19 (d, 1H), 8.66 (d, 1H), 8.87 (d, 1H). Anal. calcd. for C15H13N3O2S (299.35): C, 60.18; H, 4.38; N, 14.04; S, 10.71. Found: C, 60.00; H, 4.45; N, 14.17; S, 10.94%. Ethyl 3‐amino‐6‐(pyridin‐3‐yl)thieno[2,3‐b]pyridine‐2‐ carboxylate (18): Colorless crystals from Dioxane. Yield: 85%. M.p.: 270‐272 °C. FT‐IR (KBr, cm‐1): 3320, 3180 (NH2), 3043 (CH, aromatic), 1715 (CO), 1622 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 1.27 (t, 3H, CH2CH3), 4.23 (q, 2H, CH2CH3), 6.82 (s, br, 2H, NH2), 7.30 (t, 1H), 7.96 (d, 1H), 8.02 (t, 1H), 8.19 (d, 1H), 8.66 (d, 1H), 8.87 (d, 1H). Anal. calcd. for C15H13N3O2S (299.35): C, 60.18; H, 4.38; N, 14.04; S, 10.71. Found: C, 60.00; H, 4.45; N, 14.17; S, 10.94%. (3‐Amino‐6‐(pyridin‐3‐yl)thieno[2,3‐b]pyridin‐2‐yl)(phenyl) methanone (19): Colorless crystals from EtOH. Yield: 78%. M.p.: 210‐212 °C. FT‐IR (KBr, cm‐1): 3360, 3180 (NH2), 3043 (CH, aromatic), 1700 (CO), 1622 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 7.01 (s, br, 2H, NH2), 7.27‐7.55 (m, 6H), 7.80 (d, 1H), 8.30 (t, 1H), 8.12 (d, 1H), 8.45 (d, 1H), 9.13 (d, 1H). Anal. calcd. for C19H13N3OS (331.40), C, 68.86; H, 3.95; N, 12.68; S, 9.68. Found C, 68.65; H, 4.13; N, 12.74; S, 9.53%. 3‐Amino‐6‐(pyridin‐3‐yl)thieno[2,3‐b]pyridine‐2‐carbonitrile (20): Colorless crystals from dioxane. Yield: 71%. M.p.: 280‐ 282 °C. FT‐IR (KBr, cm‐1): 3320, 3180 (NH2), 3043 (CH, aromatic), 2148 (CN), 1623 (C=N). 1H NMR (300 MHz, DMSO‐ d6, δ, ppm): 6.92 (s, br, 2H, NH2), 7.31 (t, 1H), 7.78 (d, 1H), 8.21 (d, 1H), 8.82 (d, 1H), 8.96 (d, 1H), 9.23 (d, 1H). Anal. calcd. for C13H8N4S (252.30), C, 61.89; H, 3.20; N, 22.21; S, 12.71. Found: C, 62.00; H, 3.33; N, 22.12; S, 12.93%. 2‐(Methylthio)‐6‐(pyridin‐3‐yl)pyridine‐3‐carbonitrile (21): Colorless crystals from dioxane. Yield: 71%. M.p.: 280‐282 °C. FT‐IR (KBr, cm‐1): 3053 (CH, aromatic), 2210 (CN), 1627 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 2.45 (s, 3H, SCH3), 7.43 (t, 1H), 7.53 (t, 1H), 7.91 (d, 1H), 8.38 (d, 1H), 8.74 (d, 1H), 9.31 (d, 1H). Anal. calcd. for C12H9N3S (227.28): C, 63.41; H, 3.99; N, 18.49; S, 14.11. Found: C, 63.31; H, 4.12; N, 18.35; S, 14.00%. 512 Mohamed et al. / European Journal of Chemistry 2 (4) (2011) 509‐513 N N SCH3 CN N N S CN NH2 N N S COC6H5 NH2 21 1920 18 N N N HN NH2 i ii iii i = ClCH2COOC2H5; ii = C6H5COCH2Br; iii = ClCH2CN; iv = CH3I; v = NH2NH2.H2O v 22 N CH3 O + HCO2C2H5 CH3ONa N O ONa 15 NCCH2C(S)NH2 N N SH CN 17 N HN O CN NCCH2C(O)NH2 16 N N S CO2C2H5 NH2 iv Scheme 4 2.5. 6‐(Pyridin‐3‐yl)‐1H‐pyrazolo[3,4‐b]pyridin‐3‐amine (22) A mixture of compound 12 (2.27 g, 10 mmole) and hydrazine hydrate (4 ml, 99 %) in absolute ethanol (20 mL) for 2 hrs was heated under reflux. The reaction mixture was cooled, and the resulting solid was collected and washed with ethanol/water and recrystallized from water to give 13. Colorless crystals from water. Yield: 77%. M.p.: 105‐106 °C. FT‐ IR (KBr, cm‐1): 3043 (CH, Aromatic), 3350, 2316, 2189 (NH, NH2), 1627 (C=N). 1H NMR (300 MHz, DMSO‐d6, δ, ppm): 6.52 (s, br., 3H, NH and NH2), 7.26 (t, 1H), 7.35 (d, 1H), 8.45 (d, 1H), 8.64 (d, 1H), 8.87 (d, 1H), 9.63 (d, 1H). Anal. calcd. for C11H9N5 (211.22): C, 62.55; H, 4.29; N, 33.16. Found: C, 62.35; H, 4.12; N, 33.32%. 3. Results and discussion 2‐Acetylpyridine reacted with ethyl formate in dry ether containing sodium methoxide to give sodium salt of 3‐hydroxy‐ 1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one (2). Structure 2 was confirmed by chemical transformation. Thus, treatment of cynothioacetamide with 2 in piperidenium acetate gave 2‐(2‐ (3‐cyano‐6‐(pyridin‐2‐yl)pyridin‐2‐yl)disulfanyl)‐6‐(pyridin‐2‐ yl)pyridine‐3‐carbonitrile (3) based on elemental analysis and spectral data. 1H NMR spectrum showed signals at δ = 7.44 (t), 7.48 (m), 8.05 (d), 8.45 (d), 8.66 (d) as ratio 1: 1: 1 2: 1. IR spectrum revealed band at 3054 (CH, aromatic), 2219 (CN) group and its mass spectrum showed peak at m/z = 425 (0.6, M+1), 424 (1.7%, M), 215 (6.0%), 214 (16.5%), 213 (100%, 0.5), 212 (25.7%), 169 (49.2%), 79 (10%), 78 (33.5%) and X‐ray single crystal showed in Figure 1. Compound 3 reacted with ethyl chloroacetate in N,N‐ dimethylformamide in presence of potassium hydroxides to give ethyl 3‐amino‐6‐(2‐pyridyl)thieno[2,3‐b]pyridine‐2‐ carboxylate (4) (Scheme 1). Structure 4 was confirmed by elemental analysis and spectral data. Also, treatment of 2 with 3‐amino‐4‐phenylpyrazole in piperidenium acetate yielded 3‐phenyl‐7‐(pyridin‐2‐ yl)pyrazolo[1,5‐a]pyrimidine (9) (Scheme 2). Structure of 9 was established on the basis of their elemental analysis, spectral data and alternative synthetic routes. 1H NMR spectrum of 9 revealed signals at δ = 6.88 (d, 2H, J = 8 Hz, ArH's), 7.38 (d, 1H, J = 8 Hz, ArH), 7.56‐7.65 (m, 4H, ArH's), 7.88 (m, 1H, ArH), 8.21 (s, 1H, pyrazole H‐5), 8.62 (d, 1H, J = 8 Hz, ArH's), 8.75 (d, 1H, J = 8 Hz, ArH's), 8.93 (s, 1H, pyrimidine H‐4). Thus, treatment of 3‐(dimethylamino)‐1‐(pyridin‐2‐ yl)prop‐2‐en‐1‐one (11) with 3‐amino‐4‐phenylpyrazole in boiling ethanol gave product identical in all respects (M.p., mixed m.p., and spectra) with 9. More evidence on the formation of 9 was carried out by boiling of N,N‐dimethyl‐N'‐ (4‐phenyl‐1H‐pyrazol‐5‐yl)formamidine (10) with 2‐acetyl‐ pyridine gave product identical in all aspects (M.p., mixed m.p. and spectra) with 9. Figure 1. Molecular structure of 2‐(2‐(3‐cyano‐6‐(pyridin‐2‐yl)pyridin‐2‐ yl)disulfanyl)‐6‐(pyridin‐2‐yl)pyridine‐3‐carbonitrile (3) showing the atom numbering scheme. Thermal ellipsoids are drawn at the 50% probability level. Mohamed et al. / European Journal of Chemistry 2 (4) (2011) 509‐513 513 Scheme 5 Analogously, compound 2 reacted with the appropriate 3‐ amino‐4‐cyanopyrazole, 3‐aminotriazole or 2‐aminobenzimi‐ dazole gave 5‐(pyridin‐2‐yl)pyrazolo[1,5‐a]pyrimidine‐ 3‐carbonitrile (12), 5‐(pyridin‐2‐yl)‐[1,2,4]triazolo[1,5‐ a] pyrimidine (13) and 2‐(2‐pyridyl)‐4a‐hydropyrimidino[1,2‐ a] benzimidazole (14), respectively (Scheme 3). Meanwhile, sodium salt of 3‐hydroxy‐1‐(pyridin‐3‐yl)prop‐ 2‐en‐1‐one (15), which prepared from 3‐acetylpyridine and ethyl formate in sodium methoxide solution, reacted with each of cyanoacetamide and cynothioacetamide to give and 1,2‐ dihydro‐2‐oxo‐6‐(pyridin‐3‐yl)pyridine‐3‐carbonitrile (16) and 2‐mercapto‐6‐(pyridin‐3‐yl)pyridine‐3‐carbonitrile (17), respectively (Scheme 4). Compounds 16 and 17 were confirmed by elemental analysis, spectral data and chemical transformation. Thus, 1H NMR spectrum of 17 showed δ = 5.92 (s, 1H, SH), 7.01‐7.08 (d, 1H), 7.86‐7.90 (m, 1H), 8.00‐8.04 (m, 1H), 8.29‐8.33 (d, 1H), 8.72‐8.76 (d, 1H), 9.26‐9.26 (d, 1H) ppm. Its IR spectrum revealed bands at 2217 (CN group). On the other hand, treatment of 17 with each of ethyl chloroaceate, ω‐bromo acetophenone, chloroacetonitrile or iodomethane afforded ethyl 3‐amino‐6‐(pyridin‐3‐yl)thieno [2,3‐b]pyridine‐2‐carboxylate (18), (3‐amino‐6‐(pyridin‐3‐ yl)thieno[2,3‐b]pyridin‐2‐yl)(phenyl)methanone (19), 3‐amino‐6‐(pyridin‐3‐yl)thieno[2,3‐b]pyridine‐2‐carbonitrile (20) and 2‐(methylthio)‐6‐(pyridin‐3‐yl)pyridine‐3‐carbo‐ nitrile (21), respectively. Compound 21 could be proved via the evolution of methanethiol when treated with hydrazine hydrate, forming the sulfur free 6‐(pyridin‐3‐yl)‐1H‐ pyrazolo[3,4‐b]pyridin‐3‐amine (22). Finally, treatment of 15 with appropriate 3‐amino‐4‐ phenylpyrazole, 3‐amino‐4‐cyanopyrazole, 3‐amino‐1,3,4‐ triazole or 2‐aminobenzimidazole in piperidenium acetate yielded 3‐phenyl‐5‐(pyridin‐3‐yl)pyrazolo[1,5‐a]pyrimidine (23), 5‐(pyridin‐3‐yl)pyrazolo[1,5‐a]pyrimidine‐3‐carbonitrile (24), 5‐(pyridin‐3‐yl)‐[1,2,4]triazolo[1,5‐a]pyrimidine (25), and 2‐(3‐pyridyl)‐4a‐hydropyrimidino[1,2‐a]benzimidazole (26), respectively (Scheme 5). 4. Conclusion The present study demonstrates the synthesis of 3‐amino‐ 6‐(2‐pyridyl)thieno[2,3‐b]pyridine derivatives were synt‐ hesized via reaction of pyridine‐2‐thione. Also, pyrazolo[1,5‐a] pyrimidine, [1,2,4]triazolo[1,5‐a]pyrimidine and pyrimido [1,2‐ a]benzimidazole were synthesized by reaction of sodium salt of 3‐hydroxy‐(1‐pyridin‐2‐yl)prop‐2‐en‐1‐one or sodium salt of 3‐hydroxy‐1‐(pyridin‐3‐yl)prop‐2‐en‐1‐one with different heterocyclic amines in piperidenium acetate. 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