Synthesis of New Pyrazolo[1,5-a]pyrimidine, Triazolo[4,3-a]pyrimidine Derivatives, and Thieno[2,3-b]pyridine Derivatives from Sodium 3-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate

Abdelhamid, Abdou O.; Gomha, Sobhi M.

doi:https://doi.org/10.1155/2013/327095

Journal of Chemistry

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Research Article | Open Access

Volume 2013 | Article ID 327095 | https://doi.org/10.1155/2013/327095

Synthesis of New Pyrazolo[1,5-a]pyrimidine, Triazolo[4,3-a]pyrimidine Derivatives, and Thieno[2,3-b]pyridine Derivatives from Sodium 3-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate

Abdou O. Abdelhamid¹and Sobhi M. Gomha¹

Academic Editor: Bhimapaka C. Raju

Received30 May 2013

Revised01 Oct 2013

Accepted02 Oct 2013

Published10 Nov 2013

Abstract

Condensation of sodium 3-oxo-3-(1-phenyl-1H-pyrazol-4-yl)prop-1-en-1-olate (2) with several heterocyclic amines, cyanoacetamide, cyanothioacetamide, and 2-cyanoacetohydrazide gives pyrazolo[1,5-a]pyrimidines (5a–d), pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (9), benzo[4,5]imidazo[1,2-a]pyrimidine (10), [1,2,4]triazolo[1,5-a]pyrimidine (11), and pyridine derivatives (12–14). Also, thieno[2,3-b]pyridines (15–18) were synthesized via pyridinethione (13) with α-halo ketones and α-halo ester. Structures of the newly synthesized compounds were elucidated by elemental analysis, spectral data, alternative synthetic routes, and chemical transformation whenever possible.

1. Introduction

Several pyrazole derivatives received great attention due to their biological and pharmacological activities not only as potential inhibitors of HIV-1 [1], pesticides [2], fungicides [3], antihypertensive agents [4], and anticancer activity [5], but also as important and useful starting materials for the synthesis of other fused heterocyclic systems. Furthermore, compounds containing the pyrimidine nucleus are of significant biological importance and are used as antibacterial [6–9], antifungal [10, 11], antitumour [12, 13], antiviral [13–17], anti-inflammatory [18, 19], and antihypertensive [20–22] agents. In this work, we synthesized some new pyrazolo[1,5-a]pyrimidine, triazolo[4,3-a]pyrimidine, and thieno[2,3-b]pyridine derivatives.

2. Experimental

Melting points were measured on Electrothermal IA 9000 series digital melting point apparatus and are uncorrected. The IR spectra were recorded in potassium bromide discs on a Pye Unicam SP 3300 and Shimadzu FT IR 8101 PC infrared spectrophotometer. ¹H NMR and ¹³C NMR spectra were recorded in DMSO- using a Varian Gemini 300 NMR spectrometer (300 MHz for ¹H NMR and 75 MHz for ¹³C NMR). Mass spectra were recorded on a Shimadzu GCMS-QP1000 EX mass spectrometer at 70 eV. Elemental analysis was carried out at the Microanalytical Centre of Cairo University, Giza, Egypt. All reactions were followed by TLC (Silica gel, Merck). 1-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)ethanone [23] was prepared as reported in the literature.

2.1. Synthesis of Sodium 3-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate (2)

A mixture of (0.01 mol) 1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethanone 1 (2.0 g, 10 mmol) and ethyl formate (0.74 g, 10 mmol) was dropped over a solution of sodium methoxide (0.54 g, 10 mmol) in 20 mL dry ether with stirring. The formed solid product was collected and used directly in the following reactions.

2.2. Synthesis of 5a–d and 9–14

Method A (General Procedure). A mixture of sodium 3-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate (2) (2.5 g, 10 mmol) and the appropriate 3-amino-5-methylpyrazole 3a, 3-amino-5-phenylpyrazole 3b, 3-amino-4-cyanopyrazole 3c, 3-amino-4-methyl-5-phenylpyrazole 3d, 4,6-dimethyl-2H-pyrazolo[3,4-b]pyridin-3-amine, 2-aminobenzimidazole, 4H-1,2,4-triazol-3-amine, cyanoacetamide, cyanothioacetamide, and 2-cyanoacetohydrazide (10 mmol) and few drops of acetic acid was grinded for 10–20 min (monitored by TLC). The solid products collected by filtration and recrystallized from the suitable solvent gave the respective products 5a–d and 9–14 in an excellent yield.

Method B (General Procedure). A solution of sodium 3-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate (2) (2.5 g, 10 mmol), the appropriate 3-amino-5-methylpyrazole 3a, 3-amino-5-phenylpyrazole 3b, 3-amino-4-cyanopyrazole 3c, 3-amino-4-methyl-5-phenylpyrazole 3d, 4,6-dimethyl-2H-pyrazolo[3,4-b]pyridin-3-amine, 2-aminobenzimidazole, 4H-1,2,4-triazol-3-amine, cyanoacetamide, cyanothioacetamide, 2-cyanoacetohydrazide (10 mmol), and piperidine acetate (1 mL) in water (3 mL) was refluxed for 10 min. After completion of the reaction, the hot reaction mixture was neutralized with acetic acid (1.5 mL) and then cooled and the solid products collected by filtration and recrystallized from the suitable solvent gave products 5a–d and 9–14 in a good yield, which were identical in all aspects (m.p., mixed m.p., and spectra) with those obtained from Method A.

2.2.1. 2-Methyl-7-(5-methyl-1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine (5a)

Yield 91%; yellow crystals; mp 202–204°C (from acetic acid) (Lit. mp 202–204°C [24]).

2.2.2. 7-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-phenylpyrazolo[1,5-a]pyrimidine (5b)

Yield 90%; yellow crystals; m.p. 218-219°C (from acetic acid) (Lit. M.p. 216–218°C [24]).

2.2.3. 7-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (5c)

Yield 92%; yellow crystals; m.p. 230–232°C (from acetic acid); IR (KBr): v 1594 (C=N), 2231 (CN) cm⁻¹; ¹H NMR (DMSO-): δ 2.56 (s, 3H, CH₃), 6.38 (d, 1H, Hz, pyrimidine H-5), 6.86 (s, 1H, pyrazole H-3), 7.28–7.66 (m, 5H, ArH’s), 8.24 (s, 1H, pyrazole H-3), 8.71 (d, 1H, Hz, pyrimidine H-4); ¹³C NMR (DMSO-): δ 9.42 (CH₃), 83.11, 105.21, 111.88, 112.76, 121.87, 125.74, 128.72, 130.11, 139.88, 140.15, 128.55, 152.37, 155.18; MS m/z (%): 301(M⁺ + 1, 14), 300(M⁺, 41), 211(32), 84(76), 63(100). Anal. Calcd for C₁₇H₁₂N₆ (300.32): C, 67.99; H, 4.03; N, 27.98; Found C, 67.69; H, 4.08; N, 27.68%.

2.2.4. 3-Methyl-7-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-phenylpyrazolo[1,5-a]pyrimidine (5d)

Yield 90%; yellow crystals; m.p. 226°C (from acetic acid) (Lit. m.p. 226–228°C [25]).

2.2.5. 8,10-Dimethyl-4-(5-methyl-1-phenyl-1H-pyrazol-4-yl) pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (9)

Yield 93%; yellow crystals; m.p. 290–292°C (from acetic acid); IR (KBr): v 1588 (C=N) cm⁻¹; ¹H NMR (DMSO-): δ 2.49 (s, 3H, CH₃), 2.51 (s, 3H, CH₃), 2.74 (s, 3H, CH₃), 6.08 (d, 1H, Hz, pyrimidine H-5), 6.85 (s, 1H, pyridine H), 7.50–7.59 (m, 5H, ArH’s), 8.01 (s, 1H, pyrazole H-3), 8.24 (d, 1H, Hz, pyrimidine H-4); ¹³C NMR (DMSO-): δ 8.44 (CH₃), 19.21 (CH₃), 21.47 (CH₃), 104.19, 110.12, 112.85, 117.11, 120.78, 122.13, 126.88, 129.45, 133.12, 135.48, 139.89, 140.46, 148.74, 150.12, 151.78, 165.15; MS m/z (%): 355(M⁺ + 1, 41), 354(M⁺, 63), 262(45), 214(31), 119(28), 77(100). Anal. Calcd for C₂₁H₁₈N₆ (354.41): C, 71.17; H, 5.12; N, 23.71; Found C, 71.31; H, 5.06; N, 23.56%.

2.2.6. 4-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)benzo[4,5] imidazo[1,2-a]pyrimidine (10)

Yield 94%; yellow crystals; m.p. 203°C (from acetic acid) (Lit. m.p. 196-197°C [24]).

2.2.7. 7-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-triazolo[1,5-a]pyrimidine (11)

Yield 94%; yellow crystals; m.p. 180°C (from acetic acid) (Lit. m.p. 179-180°C [25]).

2.2.8. 6-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (12)

Yield 91%; yellow crystals; m.p. 266–268°C (from ethanol); IR (KBr): v 1614 (C=N), 2213(CN), 3393(NH) cm⁻¹; ¹H NMR (DMSO-): δ 2.48 (s, 3H, CH₃), 6.97 (d, 1H, Hz, pyridine H-5), 7.53–7.73 (m, 6H, ArH’s and pyrazole H-3), 8.18 (d, 1H, Hz, pyridine H-4), 10.21 (s, br., 1H, NH); MS m/z (%): 276(M⁺, 100), 231(34), 164(36), 118(54), 77(78). Anal. Calcd for C₁₆H₁₂N₄O (276.29): C, 69.55; H, 4.38; N, 20.28; Found C, 69.45; H, 4.23; N, 20.21%.

2.2.9. 6-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile (13)

Yield 93%; yellow crystals; m.p. 236–238°C (from ethanol); IR (KBr): v 1621 (C=N), 2218 (CN), 3420 (NH) cm⁻¹; ¹H NMR (DMSO-): δ 2.44 (s, 3H, CH₃), 6.93 (d, 1H, Hz, pyridine H-5), 7.52–7.62 (m, 6H, ArH’s and pyrazole H-3), 8.12 (d, 1H, Hz, pyridine H-4), 14.01 (s, 1H, NH); MS m/z (%): 293(M⁺ + 1, 38), 292(M⁺, 100), 264(16), 181(16), 118(26), 77(82). Anal. Calcd for C₁₆H₁₂N₄S (292.36): C, 65.73; H, 4.14; N, 19.16; Found C, 65.67; H, 4.10; N, 19.02%.

2.2.10. 1-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (14)

Yield 92%; yellow crystals; m.p. 238–140°C (from ethanol); IR (KBr): v 1603 (C=N), 2214 (CN), 3148, 3427 (NH₂) cm⁻¹; ¹H NMR (DMSO-): δ 2.52 (s, 3H, CH₃), 7.37 (d, 1H, Hz, pyridine H-5), 6.88 (s, br., 2H, NH₂), 7.50–7.56 (m, 5H, ArH’s), 7.83 (s, 1H, pyrazole H-3), 8.09 (d, 1H, Hz, pyridine H-4); ¹³C NMR (DMSO-):δ 10.89 (CH₃), 105.22, 110.46, 113.21, 118.24, 120.58, 126.87, 128.57, 128.89, 136.78, 139.25, 143.22, 146.57, 150.27; MS m/z (%): 292(M⁺ + 1, 38), 291(M⁺, 100), 118(11), 77(61). Anal. Calcd for C₁₆H₁₃N₅O (291.31): C, 65.97; H, 4.50; N, 24.04; Found C, 65.78; H, 4.54; N, 23.94%.

2.3. 3-Amino-2-substituted-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]-pyridine Derivatives (15–18)

Method A. A mixture of 13 (0.29 g, 1 mmol) and the appropriate ethyl chloroacetate, chloroacetone, ω-bromoacetophenone or chloroacetonitrile (1 mmol), and 3–5 drops of acetic acid was grinded for 15 min. The resulting solid was collected and recrystallized from ethanol to give the respective compounds, 15–18, in excellent yields.

Method B. A mixture of 13 (0.29 g, 1 mmol) and potassium hydroxide (0. 0.056 g, 1 mmol) in N,N-dimethylformamide (10 mL) was stirred for 2 h at room temperature. The appropriate ethyl chloroacetate, chloroacetone, ω-bromoacetophenone, or chloroacetonitrile (1 mmol each) was added and stirring was continued for 2 h. The resulting solid was collected and recrystallized from ethanol to give 15–18, respectively.

2.3.1. Ethyl 3-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridine-2-carboxylate (15)

Yield 88%; yellow crystals; m.p. 145-146°C; IR (KBr): v 1720 (C=O), 3320, 3418 (NH₂) cm⁻¹; ¹H NMR (DMSO-): δ 1.32 (t, Hz, 3H, CH₃CH₂), 2.49 (s, 3H, CH₃), 4.16 (q, Hz, 2H, CH₂CH₃), 7.82 (d, 1H, Hz, pyridine H-5), 7.45–7.82 (m, 7H, ArH’s and NH₂), 7.82 (s, 1H, pyrazole H-3), 8.48 (d, 1H, Hz, pyridine H-4); ¹³C NMR (DMSO-): δ11.32, 14.58, 60.12, 105.42, 117.45, 122.57, 126.51, 126.89, 127.74, 128.48, 132.25, 136.75, 140.25, 143.11, 144.87, 148.28, 155.28, 165.78; MS m/z (%): 381(M⁺ + 1, 43), 380(M⁺, 21), 176(57), 148(57), 102(57), 71(86), 53(100). Anal. Calcd for C₂₀H₁₈N₄O₂S (378.45): C, 63.47; H, 4.79; N, 14.80; Found C, 63.49; H, 4.68; N, 14.65%.

2.3.2. 1-(3-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl) thieno[2,3-b]pyridin-2-yl)ethanone (16)

Yield 86%; yellow crystals; m.p. 137-138°C; IR (KBr): v 1713 (CO), 3310, 3414 (NH₂) cm⁻¹; ¹H NMR (DMSO-): δ2.12 (s, 3H, CH₃), 2.38 (s, 3H, CH₃), 7.38–7.62 (m, 8H, ArH’s, NH₂ and pyridine H-5), 7.72 (s, 1H, pyrazole H-3), 8.59 (d, 1H, Hz, pyridine H-4); ¹³C NMR (DMSO-): δ 11.38 (CH₃), 31.25 (CH₃), 117.28, 122.58, 126.24, 126.78, 127.34, 128.48, 132.57, 136.57, 140.38, 142.28, 144.37, 147.81, 156.37, 191.28; MS m/z (%): 349(M⁺ + 1, 21), 348(M⁺, 41), 292(32), 149(38), 105(32), 77(100), 64(77). Anal. Calcd for C₁₉H₁₆N₄OS (348.42): C, 65.50; H, 4.63; N, 16.08; Found C, 65.43; H, 4.67; N, 15.87%.

2.3.3. (3-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridin-2-yl)(phenyl)methanone (17)

Yield 88%; yellow crystals; m.p. 127-128°C; IR (KBr): v 1660 (CO), 3404 (NH₂) cm⁻¹; ¹H NMR (DMSO-): δ 2.48 (s, 3H, CH₃), 7.18–7.58 (m, 14H, ArH’s, NH₂, pyrazole H-3 and pyridine H-5)), 8.54 (d, 1H, Hz, pyridine H-4); MS m/z (%): 411(M⁺ + 1, 3), 410(M⁺, 10), 293(13), 253(18), 105(100), 77(81). Anal. Calcd for C₂₄H₁₈N₄OS (410.49): C, 70.22; H, 4.42; N, 13.65; Found C, 70.18; H, 4.32; N, 13.39%.

2.3.4. 3-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridine-2-carbonitrile (18)

Yield 84%; yellow crystals; m.p. 196–198°C; IR (KBr): v 1637 (C=N), 3200 (CN), 3343, 3410 (NH₂) cm⁻¹; ¹H NMR (DMSO-): δ 2.29 (s, 3H, CH₃), 7.48–7.60 (m, 7H, ArH’s, NH₂ and pyrimidine H-5), 7.79 (s, 1H, pyrazole H-3), 8.88 (d, 1H, Hz, pyridine H-4); MS m/z (%): 331(M⁺, 10), 302(17), 179(11), 133(16), 84(100), 77(81). Anal. Calcd for C₁₈H₁₃N₅S (331.39): C, 65.24; H, 3.95; N, 21.13; Found C, 65.12; H, 3.91; N, 20.83%.

2.4. 6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2H-pyrazolo[3,4-b]pyridin-3-amine (19)

To a solution of the thione 13 (0.29 g, 0.01 mol) in ethanol (10 mL) hydrazine hydrate was added (1 mL) and the mixture was heated under reflux for 12 h. The solution was poured over ice-water mixture and then neutralized by HCl. The solid product was filtered off, dried, and recrystallized from ethanol to afford compound 15. Yield 72%; yellow crystals; m.p. 204–206°C; IR (KBr): v 1592 (C=N), 3190, 3322 (NH₂ and NH) cm⁻¹; ¹H NMR (DMSO-): δ 2.89 (s, 3H, CH₃), 5.94 (s, br., 3H, NH₂ and NH), 6.92 (d, 1H, .1 Hz, pyridine H-4), 7.48–7.56 (m, 5H, ArH’s), 8.14 (s, 1H, pyrazole H-3), 8.48 (d, 1H, .1 Hz, pyridine H-4); MS m/z (%): 291(M⁺ + 1, 18), 290(M⁺, 31), 274(52), 224(30), 171(28), 118(42), 77(100). Anal. Calcd for C₁₆H₁₄N₆ (290.32): C, 66.19; H, 4.86; N, 28.95; Found C, 66.08; H, 4.91; N, 28.76%.

2.5. 2,4-Dimethyl-8-(5-methyl-1-phenyl-1H-pyrazol-4-yl)pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (20)

To a solution of 19 (1.45 g, 5 mmol) and acetylacetone (0.5 g, 5 mmol), in acetic acid (20 mL) was refluxed for 10 min. The solid product was collected by filtration and recrystallized from acetic acid to afford compound 20. Yield 72%; yellow crystals; m.p. 206°C; IR (KBr): v 1592 (C=N) cm⁻¹; ¹H NMR (DMSO-): δ 2.19 (s, 3H, CH₃), 2.38 (s, 3H, CH₃), 2.45 (s, 3H, CH₃), 6.40 (s, 1H, pyrimidine H-5), 6.50 (d, 1H, Hz, pyridine H-5), 7.39–7.50 (m, 5H, ArH’s), 8.00 (s, 1H, pyrazole H-3), 8.40 (d, 1H, Hz, pyridine H-4); ¹³C NMR (DMSO-): δ 10.15 (CH₃), 15.68 (CH₃), 19.36 (CH₃), 104.60, 108.10, 118.00, 119.90, 122.65, 123.38, 126.00, 129.82, 134.65, 140.21, 142.95, 143.42, 146.00, 146.84, 161.10, 164.44; MS m/z (%): 355(M⁺ + 1, 1), 354(M⁺, 3), 211(12), 185(31), 157(36), 105(23), 80(100). Anal. Calcd for C₂₁H₁₈N₆ (354.41): C, 71.17; H, 5.12; N, 23.71; Found C, 71.10; H, 5.19; N, 23.56%.

3. Results and Discussion

The starting sodium 3-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate (2) was prepared via reaction of 1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethanone [23] (1) with ethyl formate in the presence of sodium methoxide. Thus, condensation of 2 with 5-amino-3-methylpyrazole (3a) in acetic acid containing piperidine acetate or grinding afforded one isolable product formulated as 2-methyl-7-(5-methyl-1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine (5a) in good yield (Scheme 1). ¹H NMR for the product revealed the signals at (s, 3H, CH₃), 2.69 (s, 3H, CH₃), 6.36 (d, 1H, Hz, pyrimidine H-5), 6.78 (s, 1H, pyrazole H-4), 7.37–7.50 (m, 5H, ArH’s), 8.45 (s, 1H, pyrazole H-3), and 8.74 (d, 1H, Hz, pyrimidine H-4). The reaction seemed to be via the initial nucleophilic attack by the exocyclic amino group at the formyl group, which formed in situ from 1 with water, followed by cyclization and elimination of one molecule of water leading to the formation of the product 5a (Scheme 1). The suggestion of the formation of the alternative isomeric product 7a is based on the initial attack of endocyclic amino group at the formyl group for the formation of 7a. As the spectroscopic data above does not allow one to distinguish between possible products 5a and 7a. The latter suggestion is excluded due to the higher nucleophilicity of the exocyclic primary amino group than the endocyclic amino group. Thus, the mechanism proposed in Scheme 1 seems to be acceptable. In order to establish unambiguously the structure of the product, the crystal structure of a similar previous work has been reported [26–29]. Also, product was obtained by an alternative synthesis route by reaction of 3-(dimethylamino)-1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-one (8) [25] with 3a. Analogously, condensation of 3b–d with 2 gave corresponding 7-substituted pyrazolo[1,5-a]pyrimidines 5b–d, respectively.

Treatment of 2 with the appropriate 4,6-dimethyl-2H-pyrazolo[3,4-b]pyridin-3-amine, 2-aminobenzimidazole, 4H-1,2,4-triazol-3-amine, cyanoacetamide and 2-cyanothioacetamide, and 2-cyanoacetohydrazide gave 8,10-dimethyl-4-(5-methyl-1-phenyl-1H-pyrazol-4-yl)pyrido [2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (9), 4-(5-methyl-1-phenyl-1H-pyrazol-4-yl)benzo[4,5]imidazo[1,2-a]pyrimidine (10), 5-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyrimidine (11), 6(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (12), 6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile (13), and 1-amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (14), respectively (Scheme 2). Structures 9–14 were confirmed by elemental analysis, spectral data, and chemical transformation whenever possible.

Thus, compound 13 reacted with each of ethyl chloroacetate, chloroacetone, ω-bromoacetophenone, chloroacetonitrile and hydrazine hydrate, afforded ethyl 3-amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridine-2-carboxylate (15), 1-(3-amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridin-2-yl)ethanone (16), (3-amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridin-2-yl)(phenyl)methanone (17), 3-amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridine-2-carbonitrile (18), and 6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (19), respectively (Scheme 3).

Structures 15–18 were elucidated by elemental analysis and spectral data. Also, compound 19 reacted with acetylacetone in acetic acid and gave 2,4-dimethyl-8-(5-methyl-1-phenyl-1H-pyrazol-4-yl)pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (20). Structure of 20 was elucidated via elemental analysis and spectral data.

4. Conclusion

In summary, we have developed a simple, efficient procedure for the synthesis of pyrazolo[1,5-a]pyrimidine, pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine, [1, 2, 4]triazolo-[1,5-a]pyrimidine, pyridine, and thieno[2,3-b]pyridines derivatives.

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Copyright © 2013 Abdou O. Abdelhamid and Sobhi M. Gomha. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Journal of Chemistry

Synthesis of New Pyrazolo[1,5-a]pyrimidine, Triazolo[4,3-a]pyrimidine Derivatives, and Thieno[2,3-b]pyridine Derivatives from Sodium 3-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate

Abstract

1. Introduction

2. Experimental

2.1. Synthesis of Sodium 3-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-3-oxoprop-1-en-1-olate (2)

2.2. Synthesis of 5a–d and 9–14

2.2.1. 2-Methyl-7-(5-methyl-1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine (5a)

2.2.2. 7-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-phenylpyrazolo[1,5-a]pyrimidine (5b)

2.2.3. 7-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (5c)

2.2.4. 3-Methyl-7-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-phenylpyrazolo[1,5-a]pyrimidine (5d)

2.2.5. 8,10-Dimethyl-4-(5-methyl-1-phenyl-1H-pyrazol-4-yl) pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (9)

2.2.6. 4-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)benzo[4,5] imidazo[1,2-a]pyrimidine (10)

2.2.7. 7-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)- triazolo[1,5-a]pyrimidine (11)

2.2.8. 6-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (12)

2.2.9. 6-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile (13)

2.2.10. 1-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (14)

2.3. 3-Amino-2-substituted-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]-pyridine Derivatives (15–18)

2.3.1. Ethyl 3-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridine-2-carboxylate (15)

2.3.2. 1-(3-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl) thieno[2,3-b]pyridin-2-yl)ethanone (16)

2.3.3. (3-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridin-2-yl)(phenyl)methanone (17)

2.3.4. 3-Amino-6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)thieno[2,3-b]pyridine-2-carbonitrile (18)

2.4. 6-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2H-pyrazolo[3,4-b]pyridin-3-amine (19)

2.5. 2,4-Dimethyl-8-(5-methyl-1-phenyl-1H-pyrazol-4-yl)pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine (20)

3. Results and Discussion

4. Conclusion

References

Copyright

2.2.7. 7-(5-Methyl-1-phenyl-1H-pyrazol-4-yl)-triazolo[1,5-a]pyrimidine (11)