An Efficient, Clean, and Catalyst-Free Synthesis of Fused Pyrimidines Using Sonochemistry

Mamaghani, M.; Tabatabaeian, K.; Araghi, R.; Fallah, A.; Hossein Nia, R.

doi:https://doi.org/10.1155/2014/406869

Organic Chemistry International

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Research Article | Open Access

Volume 2014 | Article ID 406869 | https://doi.org/10.1155/2014/406869

An Efficient, Clean, and Catalyst-Free Synthesis of Fused Pyrimidines Using Sonochemistry

M. Mamaghani,¹K. Tabatabaeian,¹R. Araghi,¹A. Fallah,²and R. Hossein Nia¹

Academic Editor: Jonathan White

Received26 Aug 2014

Accepted27 Oct 2014

Published16 Nov 2014

Abstract

In this report, synthesis of indenopyrido[2,3-d]pyrimidine and pyrimido[4,5-b]quinoline derivatives was investigated via one-pot three-component reaction between 6-amino-2-(alkylthio)-pyrimidin-4(3H)one, 1,3-indanedione, or 1,3-cyclohexadione and arylaldehyde under ultrasonic irradiation in ethylene glycol as solvent at 65°C. In these reactions fused pyrimidine derivatives were synthesized with high to excellent yields (82–97%) and short reaction times (10–33 min).

1. Introduction

Pyrimidine structural moiety constitutes a major class of heterocyclic compounds which have various pharmaceutical applications. For example, they are found to possess antineoplastic [1–3], antiviral [4–6], antibiotic [7], and anti-inflammatory properties [8]. Pyrimidines also exhibit a range of pharmacological activities such as antibacterial [9–11], antifungal [12, 13], anticancer [14, 15], and cardioprotective effects [16]. Bicyclic and tricyclic fused pyrimidine derivatives have received much attention in connection with biologically significant systems such as pyrido[2,3-d]pyrimidines. Pyrido[2,3-d]pyrimidine structural motif is present in pirenperone (tranquilizer) [17] and ramastine (antiallergic) [18], as well as in some antiulcerative and antiasthmatic agents [19]. In addition, quinolines have pharmacological properties which include wide applications in medicinal chemistry; for example, this scaffold structure is present in anti-inflammatory agents, antimalarial drugs, and antihypertensive, antiasthmatic, antibacterial, and tyrosine kinase inhibiting agents [20–25].

Moreover the importance of uracil and its annulated derivatives is well recognized by synthetic [26, 27] as well as biological [28, 29] chemists. The 6-amino-uracil derivatives represent very important classes of functionalized uracils; also 6-amino-uracils find wide applications as starting materials for the synthesis of a number of fused uracils of biological significance, for example, pyrano-, pyrido-, pyrazolo-, pyrimido-, and pyridazinopyrimidines [30, 31].

On the other hand, ultrasonic reactions have been increasingly used as clean, green, and environmentally benign routes for the preparation of organic compounds of synthetic and biological values [32–37]. A large number of organic reactions can be carried out in higher yield, shorter reaction time, and under milder conditions, by using ultrasonic irradiation [38–41].

These observations led us to attempt the synthesis of some new fused pyrimidine derivatives using 6-amino-alkyltiouracil as starting material under sonochemical conditions. The present work describes our approach for the synthesis of polyfunctional pyrimidines using green chemistry.

2. Experimental

2.1. Chemicals and Apparatus

Melting points were measured on an electrothermal 9100 apparatus. IR spectra were determined on a Shimadzo IR-470 spectrometer. ¹H NMR and ¹³C NMR spectra were recorded on a 400 MHz Bruker DRX-400 in DMSO-d₆ as solvent and TMS as an internal standard. Chemical shifts on ¹H and ¹³C NMR were expressed in ppm downfield from tetramethylsilane. Sonication was performed in Elmasonic S 40H ultrasonic cleaning unit. Elemental analyses were carried out on a Carlo-Erba EA1110CNNO-S analyser and agreed with the calculated values. All the chemicals were purchased from Merck and used without further purification. All solvents used were dried and distilled according to standard procedures.

2.2. General Procedure for the Synthesis of (4a–r)

A mixture of equimolar amounts of 6-amino-2-(alkylthio)pyrimidin-4(3H)-one 1 (1 mmol), 1,3-indanedione 2 (1 mmol), or 1,3-cyclohexadione 5 and aldehydes 3 (1 mmol) in ethylene glycol (5 mL) was placed in a Pyrex-glass open vessel and irradiated at 65°C by ultrasonic irradiations (40 kHz) (for conventional conditions, the reaction mixture was heated under reflux conditions). The progress of the reaction was monitored by TLC (EtOAc/petroleum ether 8 : 4). After completion of reaction, the mixture was concentrated and cooled. The solid obtained was filtered off and recrystallized from EtOH/H₂O (1/1) to furnish the desired pure product.

2.3. Spectral Data for the Products

2.3.1. 5-(4-Chlorophenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6(5H,11H)-dione (4a)

Red Powder; M.p.: >300°C; IR (KBr) , 3410, 3271, 3062, 2932, 1680, 1653, 1585, 1541, 1502, 1452, 1350, 1271, 1078, 899, 742, 707 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, CH₃), 4.82 (s, 1H, CH), 7.30–7.25 (m, 5H, Ar-H), 7.36 (t, 1H, J = 7.40 Hz, Ar-H), 7.45 (t, 1H, J = 7.40 Hz, Ar-H), 7.79 (d, 1H, J = 7.20 Hz, Ar-H), 11.13 (br s, 1H, NH), 12.60 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 34.2 (CH), 99.9, 107.9, 120.4, 120.9, 128.4, 130.1, 130.8, 131.2, 132.4, 133.6, 136.6, 137.5, 144.8, 153.5, 155.8, 161.5 (CONH), 191.1 (C=O) ppm. Anal. Cald. for C₂₁H₁₄ClN₃O₂S (407.87): C, 61.84; H, 3.46; N, 10.30%; Found: C, 61.95; H, 3.31; N, 10.43%.

2.3.2. 2-(Methylthio)-5-phenyl-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4b)

Red Powder; M.p.: >300°C; IR (KBr) , 3040, 2922, 2851, 1685, 1647, 1582, 1537, 1500, 1456, 1358, 1273, 742, 702 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, CH₃), 4.82 (s, 1H, CH), 7.15–7.11 (m, 1H, Ar-H), 7.26–7.21 (m, 4H, Ar-H), 7.34 (t, 2H, J = 7.40 Hz, Ar-H), 7.44 (t, 1H, J = 7.60 Hz, Ar-H), 7.78 (d, 1H, J = 7.20 Hz, Ar-H), 11.07 (br s, 1H, NH), 12.55 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 34.5 (CH), 100.0, 108.5, 120.3, 120.8, 126.6, 127.4, 128.2, 128.5, 130.6, 132.3, 133.7, 136.7, 146.0, 153.3, 155.7, 162.5 (CONH), 191.1 (C=O) ppm. Anal. Cald. for C₂₁H₁₅N₃O₂S: (373.43); C, 67.54; H, 4.05; N, 11.25%; Found: C, 67.39; H, 4.12; N, 11.12%.

2.3.3. 5-(4-Bromophenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4c)

Red Powder; M.p.: >300°C; IR (KBr): , 3300, 3100, 3080, 2920, 2820, 1690, 1640, 1618, 1558, 1498, 1440, 1348, 1270, 1070, 850, 800, 760 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, CH₃), 4.80 (s, 1H, CH), 7.21 (d, 2H, J = 7.60 Hz, Ar-H), 7.26 (d, 1H, J = 6.80 Hz, Ar-H), 7.35 (t, 1H, J = 7.20 Hz, Ar-H), 7.42 (m, 3H, Ar-H), 7.79 (d, 1H, J = 6.80 Hz, Ar-H), 11.12 (br s, 1H, NH), 12.58 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ; 13.3 (Me), 34.3 (CH), 99.9, 107.8, 119.7, 120.4, 120.9, 129.6, 130.5, 130.8, 131.3, 132.4, 133.6, 136.6, 145.2, 155.8, 162.1 (CONH), 191.1 (C=O) ppm. Anal. Cald. for C₂₁H₁₄BrN₃O₂S (452.32): C, 55.76; H, 3.12; N, 9.29%; Found: C, 55.63; H, 3.01; N, 9.38%.

2.3.4. 5-(4-Fluorophenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4d)

Red Powder; M.p.: >300°C; IR (KBr): , 3400, 3026, 2921, 2840, 1677, 1641, 1602, 1578, 1539, 1493, 1458, 1357, 1275, 1149, 843, 798, 748, 709 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, CH₃), 4.83 (s, 1H, CH), 7.07–7.01 (m, 4H, Ar-H), 7.26 (d, 2H, J = 6.40 Hz, Ar-H), 7.35 (t, 1H, J = 7.40 Hz, Ar-H), 7.45 (t, 1H, J = 7.20 Hz, Ar-H), 7.79 (d, 1H, J = 7.20 Hz, Ar-H), 11.10 (br s, 1H, NH), 12.56 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 34.0 (CH), 99.6, 108.1, 114.9 (d, Hz), 120.3, 120.7, 129.9 (d, Hz), 130.6, 132.1, 133.9, 136.8, 142.6, 153.3, 156.1, 158.9, 160.6 (d, Hz), 191.0 (C=O) ppm. Anal. Cald. for C₂₁H₁₄FN₃O₂S (391.42): C, 64.44; H, 3.61; N, 10.74%; Found: C, 64.38; H, 3.62; N, 10.85%.

2.3.5. 5-(2-Bromophenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4e)

Red Powder; M.p.: >300°C; IR (KBr): , 3300, 3110, 3080, 2920, 2820, 1690, 1645, 1618, 1558, 1498, 1440, 1347, 1270, 1070, 895, 845, 800, 760, 710 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, CH₃), 5.24 (s, 1H, CH), 7.06 (dt, 1H, J = 8.40 Hz, 2.2 Hz, Ar-H), 7.28–7.21 (m, 3H, Ar-H), 7.35 (t, 1H, J = 7.40 Hz, Ar-H), 7.48–7.43 (m, 2H, Ar-H), 7.80 (d, 1H, J = 7.20 Hz, Ar-H), 11.11 (br s, 1H, NH), 12.26 (br s, 1H, CO–NH), ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 35.7 (CH), 100.0, 107.8, 120.4, 120.7, 123.4, 128.1, 128.4, 130.7, 132.0, 132.2, 132.8, 133.6, 136.6, 136.7, 144.9, 153.7, 155.6, 162.1 (CONH), 190.7 (C=O) ppm. Anal. Cald. for C₂₁H₁₄BrN₃O₂S (452.32): C, 55.76; H, 3.12; N, 9.29%. Found: C, 55.83; H, 3.08; N, 9.45%.

2.3.6. 5-(2-Chlorophenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4f)

Red Powder; M.p.: >300°C; IR (KBr): , 3385, 3120, 3060, 2930, 2854, 1685, 1649, 1616, 1580, 1541, 1502, 1445, 1345, 1277, 1078, 893, 764 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, CH₃), 5.24 (s, 1H, CH), 7.15 (d, 1H, J = 7.20 Hz, Ar-H), 7.21 (t, 2H, J = 7.40 Hz, Ar-H), 7.29 (d, 2H, J = 7.20 Hz, Ar-H), 7.35 (t, 1H, J = 7.20 Hz, Ar-H), 7.44 (t, 1H, J = 7.20 Hz, Ar-H), 7.79 (d, 1H, J = 7.20 Hz, Ar-H), 11.10 (br s, 1H, NH), 12.49 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 33.3 (CH), 99.9, 107.6, 120.4, 120.7, 127.4, 128.1, 129.5, 130.7, 131.9, 132.2, 132.9, 133.6, 136.6, 143.1, 153.7, 155.9, 162.1 (CONH), 190.7 (C=O) ppm. Anal. Cald. for C₂₁H₁₄ClN₃O₂S (407.87): C, 61.84; H, 3.46; N, 10.30; Found: C, 61.72; H, 3.31; N, 10.18%.

2.3.7. 5-(2-Hydroxyphenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4g)

Orang Powder; M.p.: >300°C; IR (KBr): , 3270, 3050, 2920, 2820, 1700, 1645, 1620, 1600, 1560, 1500, 1440, 1347, 1280, 1180, 868, 800, 760, 700 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.59 (s, 3H, CH₃), 4.98 (s, 1H, CH), 6.72–6.69 (m, 2H, Ar-H), 7.03–7.0 (m, 2H, Ar-H), 7.25 (d, 1H, J = 6.80 Hz, Ar-H), 7.35 (t, 1H, J = 7.40 Hz, Ar-H), 7.45 (t, 1H, J = 7.40 Hz, Ar-H), 7.79 (d, 1H, J = 7.20 Hz, Ar-H), 9.58 (br s, 1H, NH), 11.12 (s, 1H, OH), 12.73 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 29.6 (CH), 100.0, 107.9, 117.5, 120.0, 120.2, 120.8, 127.9, 130.0, 130.6, 132.3, 133.8, 136.8, 136.9, 154.8, 155.0, 156.4, 156.5, 163.9 (CONH), 191.1 (C=O) ppm. Anal. Cald. for C₂₁H₁₅N₃O₃S (389.43): C, 64.77; H, 3.88; N, 10.79%; Found: C, 64.70; H, 3.98; N, 10.88%.

2.3.8. 5-(2,4-Dichlorophenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4h)

Red Powder; M.p.: >300°C; IR (KBr): , 3228, 3066, 2940, 2854, 1683, 1649, 1580, 1539, 1506, 1460, 1352, 1275, 1103, 1060, 858, 764, 704 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, CH₃), 5.22 (s, 1H, CH), 7.23 (d, 1H, J = 6.40 Hz, Ar-H), 7.37–7.27 (m, 3H, Ar-H), 7.47–7.44 (m, 2H, Ar-H), 7.80 (d, 1H, J = 7.20 Hz, Ar-H), 11.13 (br s, 1H, NH), 12.52 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 33.0 (CH), 99.4, 107.1, 120.5, 120.7, 127.6, 128.7, 130.8, 131.7, 132.2, 133.0, 133.5, 133.9, 142.3, 136.6, 153.8, 156.0, 162.0 (CONH), 190.7 (C=O) ppm. Anal. Cald. for C₂₁H₁₃Cl₂N₃O₂S: (442.32) C, 57.02; H, 2.96; N, 9.50%; Found: C, 56.88; H, 2.83; N, 9.35%.

2.3.9. 5-(2-Nitrophenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4i)

Red Powder; M.p.: >300°C; IR (KBr): , 3060, 2923, 1685, 1649, 1578, 1540, 1504, 1450, 1539, 1342, 1277, 770, 708 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, CH₃), 4.83 (s, 1H, CH), 7.05 (t, 2H, J = 8.80 Hz, Ar-H), 7.29–7.25 (m, 3H, Ar-H), 7.35 (t, 1H, J = 7.40 Hz, Ar-H), 7.45 (t, 1H, J = 7.40 Hz, Ar-H), 7.79 (d, 1H, J = 7.20 Hz, Ar-H), 11.10 (br s, 1H, NH), 12.57 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 33.9 (CH), 97.0, 108.2, 115.0, 115.2, 120.4, 120.9, 126.3, 129.9, 130.0, 130.8, 132.4, 133.6, 136.7, 142.1, 155.7, 160.0, 162.4 (CONH), 191.1 (C=O) ppm. Anal. Cald. for C₂₁H₁₄N₄O₄S (418.43) C, 60.28; H, 3.37; N, 13.39%; Found: C, 60.10; H, 3.48; N, 13.51%.

2.3.10. 5-(4-Methoxyphenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4j)

Red Powder; M.p.: >300°C; IR (KBr): , 3040, 2920, 2851, 1674, 1645, 1606, 1554, 1500, 1442, 1352, 1261, 1219, 1020, 898, 835, 766, 706 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.59 (s, 3H, CH₃), 3.68 (s, 3H, OCH₃), 4.76 (s, 1H, CH), 6.79 (d, 2H, J = 8.20 Hz, Ar-H), 7.14 (d, 2H, J = 8.20 Hz, Ar-H), 7.26 (d, 1H, J = 7.20 Hz, Ar-H), 7.35 (t, 1H, J = 7.20 Hz, Ar-H), 7.44 (t, 1H, J = 7.40 Hz, Ar-H), 7.78 (d, 1H, J = 6.80 Hz, Ar-H), 11.03 (br s, 1H, NH), 12.53 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 33.6 (CH), 55.4 (MeO), 95.0, 108.7, 112.8, 113.9, 120.2, 120.8, 129.1, 130.6, 132.3, 133.7, 136.8, 138.2, 155.4, 158.1, 161.5 (CONH), 191.2 (C=O) ppm. Anal. Cald. for C₂₂H₁₇N₃O₃S: (403.45) C, 65.49; H, 4.25; N, 10.42%; Found: C, 65.30; H, 4.35; N, 10.28%.

2.3.11. 2-(Methylthio)-5-(p-tolyl)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4k)

Red Powder; M.p.: >300°C; IR (KBr): , 3227, 3059, 2940, 2854, 1681, 1645, 1585, 1539, 1504, 1456, 1350, 1275, 897, 773 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.21 (s, 3H, CH₃), 2.59 (s, 3H, CH₃), 4.77 (s, 1H, CH), 7.03 (d, 2H, J = 7.20 Hz, Ar-H), 7.12 (d, 2H, J = 7.20 Hz, Ar-H), 7.25 (d, 1H, J = 6.40 Hz, Ar-H), 7.34 (t, 1H, J = 7.20 Hz, Ar-H), 7.44 (t, 1H, J = 7.20 Hz, Ar-H), 7.77 (d, 1H, J = 6.80 Hz, Ar-H), 11.04 (br s, 1H, NH), 12.54 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 21.0 (Me), 34.1 (CH), 100.2, 108.7, 120.2, 120.8, 128.0, 128.4, 129.0, 130.6, 132.3, 133.7, 135.6, 136.8, 143.1, 153.2, 155.5, 162.4 (CONH), 191.1 (C=O) ppm. Anal. Cald. for C₂₂H₁₇N₃O₂S: (387.45) C, 68.20; H, 4.42; N, 10.85%; Found: C, 68.38; H, 4.25; N, 10.78%.

2.3.12. 5-(3,4-Dimethoxyphenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione (4l)

Red Powder; M.p.: >300°C; IR (KBr): , 3223, 3130, 3063, 2933, 2839, 1691, 1653, 1554, 1504, 1450, 1340, 1226, 1024, 897, 798, 764, 710 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 2.60 (s, 3H, SCH₃), 3.67 (s, 3H, OCH₃), 3.71 (s, 3H, OCH₃), 4.79 (s, 1H, CH), 6.64 (d, 1H, J = 8.40 Hz, Ar-H), 6.74 (d, 1H, J = 8.40 Hz, Ar-H), 6.95 (s, 1H, Ar-H), 7.27 (d, 1H, J = 6.80 Hz, Ar-H), 7.34 (t, 1H, J = 7.20 Hz, Ar-H), 7.43 (t, 1H, J = 7.20 Hz, Ar-H), 7.77 (d, 1H, J = 7.20 Hz, Ar-H), 11.01 (br s, 1H, NH), 12.54 (br s, 1H, CO–NH) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 13.3 (Me), 33.9 (CH), 55.9 (MeO), 56.0 (MeO), 100, 108.5, 112.3, 112.6, 119.8, 120.2, 120.8, 130.6, 132.3, 133.7, 136.7, 138.6, 147.8, 148.6, 155.4, 162.5 (CONH), 191.2 (C=O) ppm. Anal. Cald. for C₂₃H₁₉N₃O₄S: (433.48) C, 63.73; H, 4.42; N, 9.69%; Found: C, 63.88; H, 4.33; N, 9.86%.

2.3.13. 5-(2,4-Dichlorophenyl)-2-(ethylthio)-5,11-dihydro-3H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-4,6-dione (4m)

Red Powder; M.p.: 282–284°C; IR (KBr): , 3136, 3059, 2966, 2926, 1649, 1607, 1550, 1502, 1450 1350, 1190, 1101, 1070, 858, 764, 700 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.36 (t, 3H, J = 7.1 Hz, CH₃), 3.22 (q, 2H, J = 7.1 Hz, CH₂), 5.22 (s, 1H, CH), 7.22 (d, 1H, J = 6.8 Hz, Ar-H), 7.46–7.26 (m, 5H, Ar-H), 7.80 (d, 1H, J = 7.2 Hz, Ar-H), 11.09 (s, 1H, NH), 12.48 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.0 (Me), 24.7 (CH₂), 33.0 (CH), 99.4, 107.1, 120.5, 127.5, 127.6, 128.7, 130.8, 131.7, 132.2, 133.0, 133.5, 133.9, 136.6, 142.3, 153.8, 156.0, 162.0 (CONH), 190.7 (C=O) ppm. Anal. Cald. for C₂₂H₁₅Cl₂N₃O₂S (456.34): C, 57.90; H, 3.31; N, 9.21%; Found: C, 57.74; H, 3.23; N, 9.05%.

2.3.14. 5-(4-Chlorophenyl)-2-(ethylthio)-5,11-dihydro-3H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-4,6-dione (4n)

Red Powder; M.p.: 268–270°C, IR (KBr): , 3140, 3063, 2876, 1649, 1545, 1504, 1452, 1350, 1188, 1146, 860, 764, 704 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.36 (t, 3H, J = 7.2 Hz, CH₃), 3.23 (q, 2H, J = 7.2 Hz, CH₂), 4.82 (s, 1H, CH), 7.26 (m, 5H, Ar-H), 7.35 (t, 1H, J = 7.2 Hz, Ar-H), 7.45 (t, 1H, J = 7.4 Hz, Ar-H), 7.79 (d, 1H, J = 7.2 Hz, Ar-H), 11.08 (s, 1H, NH), 12.56 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 24.6 (CH₂), 34.2 (CH), 99.9, 112.0, 107.9, 120.4, 120.9, 128.4, 130.1, 130.8, 131.2, 132.3, 133.5, 136.6, 144.8, 155.8, 191.1 (C=O) ppm. Anal. Cald. for C₂₂H₁₆ClN₃O₂S (421.90): C, 62.63; H, 3.82; N, 9.96%; Found: C, 62.38; H, 3.95; N, 9.76%.

2.3.15. 2-(Ethylthio)-5-(2-fluorophenyl)-5,11-dihydro-3H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-4,6-dione (4o)

Red Powder; M.p.: 257–259°C; IR (KBr): , 3132, 3057, 2932, 1684, 1647, 1583, 1539, 1491, 1350, 1263, 1182, 760, 706 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.37 (t, 3H, J = 7.2 Hz, CH₃), 3.23 (q, 2H, J = 7.2 Hz, CH₂), 5.04 (s, 1H, CH), 7.03 (m, 2H, Ar-H), 7.18 (m, 1H, Ar-H), 7.25 (t, 2H, Ar-H), 7.34 (t, 1H, J = 7.2 Hz, Ar-H), 7.44 (t, 1H, J = 7.2 Hz, Ar-H), 7.80 (d, 1H, J = 6.8 Hz, Ar-H), 11.06 (s, 1H, NH), 12.48 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 24.6 (CH₂), 29.0 (CH), 99.4, 107.4, 115.5 ( = 22.0 Hz), 120.4 ( = 10.0 Hz), 120.8, 124.6, 128.4, 128.5, 130.7, 131.1, 132.2, 132.8, 132.9, 133.6, 136.7, 153.6, 155.8 (CONH), 160.3 ( Hz), 191.0 (C=O) ppm. Anal. Cald. for C₂₂H₁₆FN₃O₂S (405.44): C, 65.17; H, 3.98; N, 10.36%; Found: C, 65.06; H, 3.81; N, 10.22%.

2.3.16. 5-(4-Bromophenyl)-2-(ethylthio)-5,11-dihydro-3H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-4,6-dione (4p)

Red Powder; M.p.: 255–257°C, IR (KBr): , 2858, 1645, 1578, 1539, 1499, 1450, 1352, 1182, 1016, 797, 708 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.36 (t, 3H, J = 7.2 Hz, CH₃), 3.23 (q, 2H, J = 7.2 Hz, CH₂), 4.81 (s, 1H, CH), 7.21 (d, 2H, J = 8.0 Hz, Ar-H), 7.26 (d, 1H, J = 7.2 Hz, Ar-H), 7.35 (t, 1H, J = 7.2 Hz, Ar-H), 7.44 (m, 3H, Ar-H), 7.79 (d, 1H, J = 7.2 Hz, Ar-H), 11.07 (s, 1H, NH), 12.55 (br s, 1H, NH–C=O) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 24.6 (CH₂), 34.4 (CH), 99.7, 107.8, 119.7, 120.4, 120.9, 130.5, 130.7, 131.3, 132.3, 133.6, 136.6, 145.2, 155.8, 161.8 (CONH), 191.0 (C=O) ppm. Anal. Cald. for C₂₂H₁₆BrN₃O₂S (466.35): C, 56.66; H, 3.46; N, 9.01%; Found: C, 56.53; H, 3.27; N, 9.16%.

2.3.17. 2-(Ethylthio)-5-(4-methylthiophenyl)-5,11-dihydro-3H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-4,6-dione (4q)

Red Powder; M.p.: 250–252°C; IR (KBr) , 3138, 3057, 2964, 2922, 1645, 1551, 1499, 1450, 1354, 1184, 835, 768, 712 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.36 (t, 3H, J = 7.2 Hz, CH₃), 2.41 (s, 3H, CH₃), 3.22 (q, 2H, J = 7.2 Hz, CH₂), 4.78 (s, 1H, CH), 7.13 (d, 2H, J = 8.0 Hz, Ar-H), 7.19 (d, 2H, J = 8.0 Hz, Ar-H), 7.26 (d, 1H, J = 7.2 Hz, Ar-H), 7.34 (t, 1H, J = 7.2 Hz, Ar-H), 7.44 (t, 1H, J = 7.4 Hz, Ar-H), 7.78 (d, 1H, J = 7.2 Hz, Ar-H), 11.03 (s, 1H, NH), 12.53 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 15.4 (Me), 24.7 (CH₂), 34.1 (CH), 100.0, 108.3, 120.3, 120.8, 126.4, 128.8, 130.6, 132.3, 133.7, 136.0, 136.7, 142.9, 153.8, 154.0, 155.5, 155.6, 191.1 (C=O) ppm. Anal. Cald. for C₂₃H₁₉N₃O₂S₂(433.55): C, 63.72; H, 4.42; N, 9.69%; Found: C, 63.57; H, 4.59; N, 9.56%.

2.3.18. 2-(Ethylthio)-5-phenyl-5,11-dihydro-3H-indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine-4,6-dione (4r)

Red Powder; M.p.: 273–276°C; IR (KBr): , 3026, 2922, 2849, 1716, 1645, 1541, 1495, 1452, 1352, 1184, 744, 710 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.36 (t, 3H, J = 7.2 Hz, CH₃), 3.23 (q, 2H, J = 7.2 Hz, CH₂), 4.82 (s, 1H, CH), 7.13 (m, 1H, Ar-H), 7.24 (m, 5H, Ar-H), 7.35 (t, 1H, J = 7.4 Hz, Ar-H), 7.44 (t, 1H, J = 7.4 Hz, Ar-H), 7.79 (d, 1H, J = 7.2 Hz, Ar-H), 11.02 (s, 1H, NH), 12.52 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 24.6 (CH₂), 34.5 (CH), 108.5, 120.3, 120.9, 126.6, 128.2, 128.5, 130.7, 132.3, 133.6, 136.6, 145.9, 155.6, 162.5 (CONH), 191.2 (C=O) ppm. Anal. Cald. for C₂₂H₁₇N₃O₂S (387.10): C, 68.26; H, 4.42; N, 10.85%; Found: C, 68.08; H, 4.55; N, 10.97%.

2.3.19. 2-(Ethylthio)-5-(4-fluorophenyl)-5,8,9,10-tetrahydro-3H,7H-pyrimido[4,5-b]quinoline-4,6-dione (6a)

White Powder; M.p.: 300–302°C; IR (KBr): , 3142, 3067, 3032, 2957, 2880, 1647, 1607, 1553, 1483, 1364, 1226, 1186, 837, 797 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.31 (t, 3H, J = 7.2 Hz, CH₃), 1.95–1.82 (m, 2H, CH₂–CH₂–CH₂), 2.29–2.18 (m, 2H, CH₂–CH₂–), 2.66–2.56 (m, 2H, CH₂–CH₂–C=O), 3.13 (q, 2H, J = 7.2 Hz, CH₂–CH₃), 4.95 (s, 1H, CH), 7.01 (t, 2H, J = 8.8 Hz, Ar-H), 7.22 (dd, 2H, J = 8.2, 5.8 Hz, Ar-H), 9.85 (s, 1H, NH), 12.33 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 21.3 (CH₂), 24.5 (CH₂), 26.9 (CH₂), 33.2 (CH₂–C=O), 37.2 (CH), 98.4, 110.9, 115.0 ( = 21.0 Hz), 129.6 ( = 8.0 Hz), 143.3 ( = 2.0 Hz), 152.4, 153.5, 153.6, 161.0 ( = 240.0 Hz), 162.2 (CONH), 195.0 (C=O) ppm. Anal. Cald. for C₁₉H₁₈FN₃O₂S (371.43): C, 61.44; H, 4.88; N, 11.31%; Found: C, 61.32; H, 4.70; N, 11.18%.

2.3.20. 2-(Ethylthio)-5-(naphthalen-2-yl)-5,8,9,10-tetrahydro-3H,7H-pyrimido[4,5-b]quinoline-4,6-dione (6b)

White Powder; M.p.: 310–312°C; IR (KBr): , 3138, 3063, 3028, 2953, 2874, 1647, 1607, 1554, 1479, 1450, 1366, 1186, 797, 752 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.31 (t, 3H, J = 7.2 Hz, CH₃), 1.94–1.85 (2H, m, CH₂–CH₂–CH₂), 2.31–2.18 (m, 2H, CH₂–CH₂–), 2.70–2.60 (m, 2H, CH₂–CH₂–C=O), 3.15 (q, 2H, J = 7.2 Hz, CH₂–CH₃), 5.12 (s, 1H, CH), 7.43 (3H, m, Ar-H), 7.62 (s, 1H, Ar-H), 7.84–7.74 (m, 3H, Ar-H), 9.88 (s, 1H, NH), 12.33 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 21.3 (CH₂), 24.5 (CH₂), 26.9 (CH₂), 27.0 (CH₂–C=O), 34.2 (CH), 98.3, 111.0, 125.7, 125.8, 126.2, 127.7, 127.2, 127.9, 128.2, 132.2, 133.2, 144.6, 153.5, 153.6, 194.9 (C=O) ppm. Anal. Cald. for C₂₃H₂₁N₃O₂S (403.50): C, 68.46; H, 5.25; N, 10.41%; Found: C, 68.60; H, 5.17; N, 10.55%.

2.3.21. 2-(Ethylthio)-5-(p-tolyl)-5,8,9,10-tetrahydro-3H,7H-pyrimido[4,5-b]quinoline-4,6-dione (6c)

White Powder; M.p.: 292–294°C; IR (KBr): , 3142, 3067, 2878, 1649, 1614, 1556, 1475, 1366, 1186, 794 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.31 (t, 3H, J = 7.2 Hz, CH₃–CH₂), 1.92–1.80 (m, 2H, CH₂–CH₂–CH₂), 2.3–2.1 (m, 5H, CH₂–CH₂– and CH₃-Ar), 2.65–2.57 (m, 2H, CH₂–CH₂–C=O), 3.14 (q, 2H, J = 7.2 Hz, CH₂–CH₃), 4.90 (s, 1H, CH), 6.99 (d, 2H, J = 7.6 Hz, Ar-H), 7.08 (d, 2H, J = 7.6 Hz, Ar-H), 9.79 (s, 1H, NH), 12.31 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 21.0 (Me), 21.3 (CH₂), 24.5 (CH₂), 26.8 (CH₂), 26.9 (CH₂–C=O), 33.3 (CH), 98.6, 111.2, 127.8, 128.9, 135.2, 144.2, 153.2, 153.3, 194.8 (C=O) ppm. Anal. Cald. for C₂₀H₂₁N₃O₂S (367.46): C, 65.37; H, 5.76; N, 11.41%; Found: C, 65.21; H, 5.52; N, 11.25%.

2.3.22. 2-(Ethylthio)-5-(4-methoxyphenyl)-5,8,9,10-tetrahydro-3H,7H-pyrimido[4,5-b]quinoline-4,6-dione (6d)

White Powder; M.p.: 288–290°C; IR (KBr): , 3140, 3067, 3030, 2949, 1649, 1608, 1553, 1479, 1366, 1184, 1230, 1034, 835 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.31 (t, 3H, J = 7.2 Hz, CH₃), 1.95–1.81 (m, 2H, CH₂–CH₂–CH₂), 2.23 (m, 2H, CH₂–CH₂–), 2.60–2.55 (m, 2H, CH₂–CH₂–C=O), 3.13 (q, 2H, J = 7.2 Hz, CH₂–CH₃), 3.67 (s, 3H, OCH₃), 4.89 (s, 1H, CH), 6.75 (d, 2H, J = 8.4 Hz, Ar-H), 7.10 (d, 2H, J = 8.4 Hz, Ar-H), 9.78 (s, 1H, NH), 12.30 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 21.3 (MeO), 24.5 (CH₂), 26.9 (CH₂), 32.8 (CH₂), 37.2 (CH₂–C=O), 55.4 (CH), 98.8, 111.3, 113.7, 128.8, 139.5, 153.1, 153.2, 157.9, 162.0 (CONH), 194.8 (C=O) ppm. Anal. Cald. for C₂₂H₂₁N₃O₂S (383.46): C, 62.64; H, 5.52; N, 10.96%; Found: C, 62.64; H, 5.58; N, 1085%.

2.3.23. 2-(Ethylthio)-5-(5-methylthiophen-2-yl)-5,8,9,10-tetrahydro-3H,7H-pyrimido[4,5-b]quinoline-4,6-dione (6e)

White Powder; M.p.: 280–282°C; IR (KBr): , 3138, 3067, 3030, 2951, 2872, 1649, 1607, 1553, 1479, 1448, 1364, 1182, 798 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.32 (t, 3H, J = 7.2 Hz, CH₃), 1.98–1.85 (m, 2H, CH₂–CH₂–CH₂–), 2.27 (m, 2H, CH₂–CH₂–), 2.30 (s, 3H, CH₃-Ar), 2.62–2.54 (m, 2H, CH₂–CH₂–C=O), 3.13 (q, 2H, J = 7.2 Hz, CH₂–CH₃), 5.15 (s, 1H, CH), 6.48 (s, 2H, Ar-H), 9.90 (s, 1H, NH), 12.41 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 15.4 (Me), 21.3 (CH₂), 24.6 (CH₂), 26.9 (CH₂), 28.6 (CH₂–C=O), 37.2 (CH), 98.0, 110.6, 123.0, 125.0, 137.0, 148.6, 152.5, 153.4, 162.0 (CONH), 194.7 (C=O) ppm. Anal. Cald. for C₁₈H₁₉N₃O₂S₂(373.09): C, 57.88; H, 5.13; N, 11.25%; Found: C, 57.95; H, 5.20; N, 11.10%.

2.3.24. 5-(4-Chlorophenyl)-2-(ethylthio)-5,8,9,10-tetrahydro-3H,7H-pyrimido[4,5-b]quinoline-4,6-dione (6f)

White Powder; M.p.: 262–265°C; IR (KBr) , 3182, 3045, 2941, 2822, 1647, 1553, 1500, 1454, 1342, 1188, 1063, 825 cm⁻¹. ¹H NMR (400 MHz, DMSO-d₆): δ = 1.31 (t, 3H, J = 7.2 Hz, CH₃), 1.95–1.82 (m, 2H, CH₂–CH₂–CH₂), 2.25–2.21 (m, 2H, CH₂–CH₂–), 2.65–2.55 (m, 2H, CH₂–CH₂–C=O), 3.13 (q, 2H, J = 7.2 Hz, CH₂–CH₃), 4.92 (s, 1H, CH), 7.21 (d, 2H, J = 8.4 Hz, Ar-H), 7.25 (d, 2H, J = 8.4 Hz, Ar-H), 9.86 (s, 1H, NH), 12.36 (br s, 1H, NH–C=O) ppm. ¹³C NMR (100 MHz, DMSO-d₆): δ = 15.1 (Me), 21.2 (CH₂), 24.6 (CH₂), 26.8 (CH₂), 33.6 (CH₂–C=O), 37.1 (CH), 98.1, 110.7, 110.7, 128.2, 129.8, 130.8, 131.6, 146.0, 153.6, 153.7, 194.9 (C=O) ppm. Anal. Cald. for C₁₉H₁₈ClN₃O₂S (387.89): C, 58.83; H, 4.68; N, 10.83%; Found: C, 58.70; H, 4.47; N, 10.68%.

3. Results and Discussion

As part of our continuing efforts on the development of new synthetic strategies for the preparation of heterocyclic compounds [42–48], herein we wish to report one-pot three-component synthesis of fused pyridopyrimidines under sonochemical conditions without the use of catalyst (Schemes 1 and 2).

In the initial experiment, to optimize the reaction conditions, different solvents were screened for the synthesis of 5-(4-chlorophenyl)-2-(methylthio)-3H-indeno[5,6:1′,2′]pyrido[2,3-d]pyrimidine-4,6 (5H,11H)-dione 4a as a model reaction. The reaction between equimolar amounts of 6-amino-2-(methylthio)pyrimidin-4(3H)-one 1 (prepared by the condensation of thiourea with ethylcyanoacetate in sodium ethoxide and followed by alkylation with alkyliodide [49]), 1,3-indanedione 2, and 4-chlorobenzaldehyde were examined in various solvents and different temperatures (25, 50, 65, and 80°C) under sonochemical conditions. The results of this study are summarized in Table 1. It is evident from the results that ethylene glycol is the most effective solvent among the selected solvents, giving the highest yield (95%) and lower reaction time (25 min) under ultrasound irradiation (entry 1). For comparison, the preparation of 4a was carried out under conventional heating at reflux conditions which furnished the desired product at lower yield and much higher reaction time (180 min) (Table 1, entry 1). The results revealed that the reaction induced by ultrasonic irradiations offered better result than the conventional condition (Figure 1).

Using the optimized reaction conditions various derivatives of indenopyrido[2,3-d]pyrimidines 4a–r (Scheme 1) were prepared in high to excellent yields (85–97%) and lower reaction times (Table 2).

Due to remarkable results from the above experiments, we decided to broaden the scope of this protocol for the synthesis of quinoline derivatives as another fused pyrimidine derivative. We investigated the reaction between 6-amino-2-(ethylthio)pyrimidin-4(3H)-one 1, 1,3-cyclohexadione 5, and arylaldehydes 3 under the aforementioned optimized reaction conditions and obtained pyrimido[4,5-b]quinoline-4,6-diones 6a–f (Scheme 2) in high yields (82–95%) and short reaction times (10–25 min) (Table 3).

The plausible mechanism of this MCRs involves Knoevenagel condensation between CH-acid (2 or 5) and aryl aldehydes (3) resulting in the arylidene intermediate 7, followed by Michael addition of enaminone 1, cyclization, and removal of H₂O to form the desired products (4 or 6) (Scheme 3).

All the synthesized pyridopyrimidine derivatives were characterized on the basis of elemental and spectral (¹H NMR, ¹³C NMR, and IR) analyses.

4. Conclusion

In summary, we have developed a simple, green, and efficient protocol for the synthesis of novel fused derivatives of pyrimidine under ultrasonic irradiations. The easy work of the products, without the use of catalyst, mild reaction condition, high to excellent yields, short reaction times, and cleaner reaction profiles are the notable features of this protocol. The method is amenable for the iterative generation of combinatorial libraries.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgments

The authors are grateful to the Research Council of University of Guilan and Islamic Azad University, Rasht Branch, for financial support of this work.

References

S. A. Giller, R. A. Zhuk, and M. I. U. Lidak, “Analogs of pyrimidine nucleosides. I. N₁-(alpha-furanidyl) derivatives of natural pyrimidine bases and their antimetabolities,” Doklady Akademii nauk SSSR, vol. 176, no. 2, pp. 332–335, 1967.
View at: Google Scholar
A. R. Curreri, F. J. Ansfield, F. A. McIver, H. A. Waisman, and C. Hedelberger, “Clinical studies with 5-fluorouracil,” Cancer Research, vol. 18, no. 4, pp. 478–484, 1958.
View at: Google Scholar
N. K. Chaudhary, B. J. Montag, and C. Heidelberger, “Studies on fluorinated pyrimidines: III. The metabolism of 5-fluorouracil-2-C¹⁴ and 5-fluoroorotic-2-C¹⁴ acid in vivo,” Cancer research, vol. 18, no. 3, pp. 318–328, 1958.
View at: Google Scholar
V. Malik, P. Singh, and S. Kumar, “Unique chlorine effect in regioselective one-pot synthesis of 1-alkyl-/allyl-3-(o-chlorobenzyl) uracils: anti-HIV activity of selected uracil derivatives,” Tetrahedron, vol. 62, no. 25, pp. 5944–5951, 2006.
View at: Google Scholar
A. Holý, I. Votruba, M. Masojídková et al., “6-[2-(Phosphonomethoxy)alkoxy] pyrimidines with antiviral activity,” Journal of Medicinal Chemistry, vol. 45, no. 9, pp. 1918–1929, 2002.
View at: Publisher Site | Google Scholar
P. Andres and A. Marhold, “A new synthesis of 5-trifluoromethyluracil,” Journal of Fluorine Chemistry, vol. 77, no. 1, pp. 93–95, 1996.
View at: Publisher Site | Google Scholar
J. J. Reddick, S. Saha, J.-M. Lee, J. S. Melnick, J. Perkins, and T. P. Begley, “The mechanism of action of bacimethrin, a naturally occurring thiamin antimetabolite,” Bioorganic and Medicinal Chemistry Letters, vol. 11, no. 17, pp. 2245–2248, 2001.
View at: Publisher Site | Google Scholar
B. Gauthier, “On the thiamines with an open thiazole ring. study of O, S-diacetylthiamine,” Annales Pharmaceutiques Françaises, vol. 21, pp. 655–666, 1963.
View at: Google Scholar
E. Wyrzykiewicz, G. Bartkowiak, Z. Nowakowska, and B. Kedzia, “Synthesis and antimicrobial properties of S-substituted derivatives of 2-thiouracil,” Farmaco, vol. 48, no. 7, pp. 979–988, 1993.
View at: Google Scholar
P. Sharma, N. Rane, and V. K. Gurram, “Synthesis and QSAR studies of pyrimido[4,5-d]pyrimidine-2,5-dione derivatives as potential antimicrobial agents,” Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 16, pp. 4185–4190, 2004.
View at: Publisher Site | Google Scholar
Y. M. Elkholy and M. A. Morsy, “Facile synthesis of 5, 6, 7, 8-tetrahydropyrimido [4, 5-b]-quinoline derivatives,” Molecules, vol. 11, no. 11, pp. 890–903, 2006.
View at: Publisher Site | Google Scholar
B. S. Holla, M. Mahalinga, M. S. Karthikeyan, P. M. Akberali, and N. S. Shetty, “Synthesis of some novel pyrazolo[3,4-d]pyrimidine derivatives as potential antimicrobial agents,” Bioorganic and Medicinal Chemistry, vol. 14, no. 6, pp. 2040–2047, 2006.
View at: Publisher Site | Google Scholar
N. Ingarsal, G. Saravanan, P. Amutha, and S. Nagarajan, “Synthesis, in vitro antibacterial and antifungal evaluations of 2-amino-4-(1-naphthyl)-6-arylpyrimidines,” European Journal of Medicinal Chemistry, vol. 42, no. 4, pp. 517–520, 2007.
View at: Publisher Site | Google Scholar
X. L. Zhao, Y. F. Zhao, S. C. Guo, H. S. Song, D. Wang, and P. Gong, “Synthesis and anti-tumor activities of novel [1,2,4]triazolo[1,5-a] pyrimidines,” Molecules, vol. 12, no. 5, pp. 1136–1146, 2007.
View at: Publisher Site | Google Scholar
L. Cordeu, E. Cubedo, E. Bandrés et al., “Biological profile of new apoptotic agents based on 2,4-pyrido[2,3-d]pyrimidine derivatives,” Bioorganic and Medicinal Chemistry, vol. 15, no. 4, pp. 1659–1669, 2007.
View at: Publisher Site | Google Scholar
N. M. Khalifa, N. S. Ismail, and M. M. Abdulla, “Synthesis and reactions of fused cyanopyrimidine derivatives and related glycosides as antianginal and cardio protective agents,” Egyptian Pharmaceutical Journal, vol. 4, pp. 277–288, 2005.
View at: Google Scholar
R. L. Smith, R. J. Barrett, and E. Sanders-Bush, “Neurochemical and behavioral evidence that quipazine-ketanserin discrimination is mediated by serotonin 2A receptor,” Journal of Pharmacology and Experimental Therapeutics, vol. 275, no. 2, pp. 1050–1057, 1995.
View at: Google Scholar
F. Awouters, J. Vermeire, F. Smeyers et al., “Oral antiallergic activity in ascaris hypersensitive dogs: a study of known antihistamines and of the new compounds ramastine (R 57 959) and levocabastine (R 50 547),” Drug Development Research, vol. 8, no. 1–4, pp. 95–102, 1986.
View at: Publisher Site | Google Scholar
Y. Yanagihara, H. Kasai, T. Kawashima, and T. Shida, “Immunopharmacological studies on TBX, a new antiallergic drug (1). Inhibitory effects on passsive cutaneous anaphylaxis in rats and guinea pigs,” The Japanese Journal of Pharmacology, vol. 48, no. 1, pp. 91–101, 1988.
View at: Publisher Site | Google Scholar
R. D. Larsen, E. G. Corley, A. O. King et al., “Practical route to a new class of LTD4 receptor antagonists,” The Journal of Organic Chemistry, vol. 61, no. 10, pp. 3398–3405, 1996.
View at: Publisher Site | Google Scholar
Y.-L. Chen, K.-C. Fang, J.-Y. Sheu, S.-L. Hsu, and C.-C. Tzeng, “Synthesis and antibacterial evaluation of certain quinolone derivatives,” Journal of Medicinal Chemistry, vol. 44, no. 14, pp. 2374–2377, 2001.
View at: Publisher Site | Google Scholar
G. Roma, M. Di Braccio, G. Grossi, F. Mattioli, and M. Ghia, “1 ,8 -Naphthyridines IV. 9-Substituted N, N -dialkyl-5-(alkylamino or cycloalkylamino) [1,2,4] triazolo [4,3- a][1,8]naphthyridine-6-carboxamides, new compounds with anti-aggressive and potent anti-inflammatory activities,” European Journal of Medicinal Chemistry, vol. 35, no. 11, pp. 1021–1035, 2000.
View at: Publisher Site | Google Scholar
D. Dubé, M. Blouin, C. Brideau et al., “Quinolines as potent 5-lipoxygenase inhibitors: synthesis and biological profile of L-746,530,” Bioorganic & Medicinal Chemistry Letters, vol. 8, no. 10, pp. 1255–1260, 1998.
View at: Publisher Site | Google Scholar
M. P. Maguire, K. R. Sheets, K. McVety, A. P. Spada, and A. Zilberstein, “A new series of PDGF receptor tyrosine kinase inhibitors: 3-Substituted quinoline derivatives,” Journal of Medicinal Chemistry, vol. 37, no. 14, pp. 2129–2137, 1994.
View at: Publisher Site | Google Scholar
O. Billker, V. Lindo, M. Panico et al., “Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito,” Nature, vol. 392, no. 6673, pp. 289–292, 1998.
View at: Publisher Site | Google Scholar
T. K. Bradshaw and D. W. Hutchinson, “5-Substituted pyrimidine nucleosides and nucleotides,” Chemical Society Reviews, vol. 6, no. 1, pp. 43–62, 1977.
View at: Publisher Site | Google Scholar
T. Sasaki, K. Minamoto, T. Suzuki, and S. Yamashita, “Search for a simpler synthetic model system for intramolecular 1,3-dipolar cycloaddition to the 5,6-double bond of a pyrimidine nucleoside,” Tetrahedron, vol. 36, no. 7, pp. 865–870, 1980.
View at: Publisher Site | Google Scholar
R. Marumoto and Y. Furukawa, “Kondensierte pyrimidine. III. Synthese von Isoxazolo [3, 4-d] pyrimidinen,” Chemical and Pharmaceutical Bulletin, vol. 25, no. 11, pp. 2974–2982, 1977.
View at: Google Scholar
H. Griengl, E. Wanek, W. Schwarz, W. Streicher, B. Rosenwirth, and E. De Clercq, “2′-Fluorinated arabinonucleosides of 5-(2-haloalkyl)uracil: synthesis and antiviral activity,” Journal of Medicinal Chemistry, vol. 30, no. 7, pp. 1199–1204, 1987.
View at: Publisher Site | Google Scholar
G. Shaw, Comprehensive Heterocyclic Chemistry, Volume 3, A. R. Katritzky, C.W. Rees, Eds., p. 57, Pergamon, Oxford, UK, 1984.
A. Agarwal and P. M. S. Chauhan, “Solid supported synthesis of structurally diverse dihydropyrido[2,3-d] pyrimidines using microwave irradiation,” Tetrahedron Letters, vol. 46, no. 8, pp. 1345–1348, 2005.
View at: Publisher Site | Google Scholar
G. H. Mahdavinia, S. Rostamizadeh, A. M. Amani, and Z. Emdadi, “Ultrasound-promoted greener synthesis of aryl-14-H-dibenzo[a,j]xanthenes catalyzed by NH₄H₂PO₄/SiO₂ in water,” Ultrasonics Sonochemistry, vol. 16, no. 1, pp. 7–10, 2009.
View at: Publisher Site | Google Scholar
G. Cravotto and P. Cintas, “Power ultrasound in organic synthesis: moving cavitational chemistry from academia to innovative and large-scale applications,” Chemical Society Reviews, vol. 35, no. 2, pp. 180–196, 2006.
View at: Publisher Site | Google Scholar
T. J. Mason and J. P. Lorimer, Applied Sonochemistry: The Uses of Power Ultrasound in Chemistry and Processing, Wiley-VCH, 2002.
D. Mantu, C. Moldoveanu, A. Nicolescu, C. Deleanu, and I. I. Mangalagiu, “A facile synthesis of pyridazinone derivatives under ultrasonic irradiation,” Ultrasonics Sonochemistry, vol. 16, no. 4, pp. 452–454, 2009.
View at: Publisher Site | Google Scholar
J. T. Li, Y. Yin, L. Li, and M. X. Sun, “A convenient and efficient protocol for the synthesis of 5-aryl-1,3-diphenylpyrazole catalyzed by hydrochloric acid under ultrasound irradiation,” Ultrasonics Sonochemistry, vol. 17, no. 1, pp. 11–13, 2010.
View at: Google Scholar
L. Pizzuti, P. L. G. Martins, B. A. Ribeiro et al., “Efficient sonochemical synthesis of novel 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides,” Ultrasonics Sonochemistry, vol. 17, no. 1, pp. 34–37, 2010.
View at: Publisher Site | Google Scholar
C.-L. Ni, X.-H. Song, H. Yan, X.-Q. Song, and R.-G. Zhong, “Improved synthesis of diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylate under ultrasound irradiation,” Ultrasonics Sonochemistry, vol. 17, no. 2, pp. 367–369, 2010.
View at: Publisher Site | Google Scholar
A. Bazgir, S. Ahadi, R. Ghahremanzadeh, H. R. Khavasi, and P. Mirzaei, “Ultrasound-assisted one-pot, three-component synthesis of spiro[indoline-3,4′-pyrazolo[3,4-b]pyridine]-2,6′(1′H)-diones in water,” Ultrasonics Sonochemistry, vol. 17, no. 2, pp. 447–452, 2010.
View at: Publisher Site | Google Scholar
Z.-H. Zhang, J.-J. Li, and T.-S. Li, “Ultrasound-assisted synthesis of pyrroles catalyzed by zirconium chloride under solvent-free conditions,” Ultrasonics Sonochemistry, vol. 15, no. 5, pp. 673–676, 2008.
View at: Publisher Site | Google Scholar
A. R. Khosropour, “Ultrasound-promoted greener synthesis of 2,4,5-trisubstituted imidazoles catalyzed by Zr(acac)₄ under ambient conditions,” Ultrasonics Sonochemistry, vol. 15, no. 5, pp. 659–664, 2008.
View at: Publisher Site | Google Scholar
R. H. Nia, M. Mamaghani, F. Shirini, and K. Tabatabaeian, “A convenient one-pot three-component approach for regioselective synthesis of novel substituted pyrazolo[1,5-a]pyrimidines using Fe⁺³-montmorillonite as efficient catalyst,” Journal of Heterocyclic Chemistry, vol. 51, no. 2, pp. 363–367, 2014.
View at: Publisher Site | Google Scholar
M. Mamaghani, F. Shirini, N. O. Mahmoodi, A. Azimi-Roshan, and A. Monfared, “‘on water’ organic synthesis: three-component one-pot synthesis of novel bis(1-(cyclohexylamino)-1-oxoalkyl or aryl) fumarates,” Journal of the Iranian Chemical Society, vol. 11, no. 3, pp. 659–664, 2014.
View at: Publisher Site | Google Scholar
M. Mamaghani, F. Shirini, N. O. Mahmoodi, A. Azimi-Roshan, and H. Hashemlou, “A green, efficient and recyclable Fe⁺³@K10 catalyst for the synthesis of bioactive pyrazolo[3,4-b]pyridin-6(7H)-ones under “on water” conditions,” Journal of Molecular Structure, vol. 1051, pp. 169–176, 2013.
View at: Publisher Site | Google Scholar
R. Hossein Nia, M. Mamaghani, K. Tabatabaeian, F. Shirini, and M. Rassa, “An expeditious regioselective synthesis of novel bioactive indole-substituted chromene derivatives via one-pot three-component reaction,” Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 18, pp. 5956–5960, 2012.
View at: Publisher Site | Google Scholar
M. Mamaghani, A. Loghmanifar, and M. R. Taati, “An efficient one-pot synthesis of new 2-imino-1,3-thiazolidin-4-ones under ultrasonic conditions,” Ultrasonics Sonochemistry, vol. 18, no. 1, pp. 45–48, 2011.
View at: Publisher Site | Google Scholar
M. Nikpassand, M. Mamaghani, F. Shirini, and K. Tabatabaeian, “A convenient ultrasound-promoted regioselective synthesis of fused polycyclic 4-aryl-3-methyl-4,7-dihydro-1H-pyrazolo[3,4-b]pyridines,” Ultrasonics Sonochemistry, vol. 17, no. 2, pp. 301–305, 2010.
View at: Publisher Site | Google Scholar
M. Mamaghani, N. O. Mahmoodi, F. Shirini, A. Azimi-Roshan, and A. Monfared, “On water sonochemical multicomponent synthesis of novel bioactive 1,1′-(Aryl)bis(2-(cyclohexylamino)-2-oxoethane-1,1-diyl) Di(alkanoates and benzoates),” Journal of Chemistry, vol. 2013, Article ID 125959, 8 pages, 2013.
View at: Publisher Site | Google Scholar
P. Crepaldi, B. Cacciari, M.-C. Bonache et al., “6-Amino-2-mercapto-3H-pyrimidin-4-one derivatives as new candidates for the antagonism at the P2Y₁₂ receptors,” Bioorganic & Medicinal Chemistry, vol. 17, no. 13, pp. 4612–4621, 2009.
View at: Publisher Site | Google Scholar

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Copyright © 2014 M. Mamaghani et al. 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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