Abstract
A one-pot, three-component reaction of 4-hydroxycoumarin, arylglyoxals, and 6-aminouracil or 1,3-dimethyl-6-aminouracil in the presence of L-proline as an organocatalyst in acetic acid under reflux conditions provided a series of new pyrrolo[3,2-d]pyrimidine derivatives in good yields.
Introduction
Pyrrolo[3,2-d]pyrimidines have many pharmaceutical applications. They are antitumor [1], antimicrobial [2], antibacterial [3], antifolate [4], anticonvulsant [5], antileishmanial [6], anti-inflammatory [7], antiaggressive [8], antiviral [9], anticoagulant [10], antioxidant [11], antifungal [12], antiasthmatic [13] and anti-HIV agents [14]. In continuation of our interests in the preparation of heterocyclic compounds by one-pot, multicomponent reactions [15], [16], [17], [18], [19], [20], herein we report the synthesis of coumarinyl-substituted pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione derivatives 4a–n (Scheme 1) by a one-pot, three-component reaction of 4-hydroxycoumarin, arylglyoxals and 6-aminouracil or 1,3-dimethyl-6-aminouracil in the presence of L-proline as an organocatalyst.
![Scheme 1 Synthesis of pyrrolo[3,2-d]pyrimidine derivatives 4a–n.](/document/doi/10.1515/hc-2017-0187/asset/graphic/j_hc-2017-0187_scheme_001.jpg)
Synthesis of pyrrolo[3,2-d]pyrimidine derivatives 4a–n.
Results and discussion
Bharti [21] has recently reported that the three-component reaction of 4-hydroxycoumarin, an aldehyde and 1,3-dimethyl-6-aminouracil in the presence of a catalytic amount of L-proline in ethanol under reflux conditions provided 6-amino-5-[(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-1,3-dimethylpyrimidine-2,4(1H,3H)-dione. It was of interest to replace the aldehyde with an arylglyoxal in this reaction. Arylglyoxals are efficiently synthesized in the form of hydrates by the oxidation of acetophenones with selenium dioxide in ethanol under reflux conditions [20]. While this work was in progress, Choudhury and coworkers [22] reported that the treatment of 4-hydroxycoumarin (1) with an arylglyoxal 2 and 1,3-dimethyl-6-aminouracil (3) in AcOH under microwave conditions furnished pyrrolo[2,3-d]pyrimidine derivatives 4h, 4k and 4m. In this paper, we report the one-pot, three-component reaction of 4-hydroxycoumarin (1), arylglyoxal 2 and 6-aminouracil or 1,3-dimethyl-6-aminouracil (3) leading to pyrrolo[2,3-d]pyrimidine derivatives 4a–n efficiently catalyzed by L-proline (Scheme 1).
The reaction of 4-hydroxycoumarin (1), phenylglyoxal (2a) and 6-aminouracil (3) was chosen as the model reaction. In the absence of L-proline, no product was observed at room temperature even after 24 h. Refluxing the reaction mixture in acetic acid without the catalyst for 7 h gave the desired product 4a in only a 14% yield. The product was fully characterized by its Fourier-transform infrared spectroscopy (FT IR), 1H nuclear magnetic resonance (1H NMR) and 13C NMR spectral data. The use of increasing amounts of L-proline as an organocatalyst gradually improved the yield. Under optimized conditions, the reaction was conducted in acetic acid under reflux for 7 h and furnished product 4a in a 73% yield. This reaction was attempted in the presence of other catalysts including K2CO3 (21% yield), triethylenediamine (41% yield), 4-dimethylaminopyridine (35% yield), pyrrolidine (38% yield), tetra-n-butyl ammonium bromide (48% yield), sodium dodecyl sulfate (31% yield), ZrOCl2 (45% yield) and p-toluenesulfonic acid (46% yield) using acetic acid as a solvent. As can be seen, the use of L-proline proved to be the best in terms of yield. The model reaction in the presence of L-proline was also conducted in ethanol/water (31% yield), ethanol (35% yield), acetonitrile (32% yield), water (41% yield), dichloromethane (trace amount of 4a) and tetrahydrofuran (trace amount of 4a). Thus, the highest yield of 4a (73%) was obtained from the reaction conducted in acetic acid.
Mechanistically (Scheme 2), the formation of product 4a–n can be explained in terms of the Knoevenagel condensation of hydroxycoumarin with the aryglyoxal, catalyzed by L-proline, followed by Michael addition of 6-aminouracil or 1,3-dimethyl-6-aminouracil to the Knoevenagel intermediate product and then intramolecular heterocyclization of the Michael product.
The proposed mechanism for 4a–n.
Conclusion
Pyrrolo[3,2-d]pyrimidine derivatives 4a–n were synthesized by the one-pot, three-component reaction of 4-hydroxycoumarin, arylglyoxal and 1,3-dimethyl-6-aminouracil or 6-aminouracil using 20 mol% of L-proline as an organocatalyst in acetic acid under reflux.
Experimental
The solvents were distilled and dried according to Perrin and Armarego [23]. The melting points were measured on an Electrothermal 9200 apparatus and are uncorrected. FT-IR spectra were recorded on a Thermo Nicolet (Nexus 670) spectrometer using KBr discs. The 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were recorded on a Bruker DRX-300 Avance spectrometer in DMSO-d6 with tetramethylsilane (TMS) as the internal reference. Elemental analyses were performed using a Leco Analyzer 932.
Arylglyoxals were obtained in the form of hydrates by the oxidation of acetophenones with selenium dioxide in ethanol under reflux conditions as previously reported [20].
General procedure for synthesis of pyrrolo[3, 2-d] pyrimidine derivatives 4a–n
A mixture of 4-hydroxycoumarin (1, 1 mmol), arylglyoxal hydrate (2, 1 mmol), 6-aminouracil or 1,3-dimethyl-6-aminouracil (3, 1 mmol) and L-proline (0.2 mmol) in acetic acid (5 mL) was heated under reflux for 4h (4i), 5h (4b and 4l), 6h (4c, 4e, 4h, 4j and 4k), 7h (4a, 4d, 4m and 4n) and 8 h (4f and 4g). The reaction was monitored by thin-layer chromatography (TLC) eluting with EtOAc/hexanes (3:1). After the completion of the reaction, the resultant precipitate was filtered, washed with acetic acid and cold water, dried and crystallized from ethanol.
6-(Phenyl)-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-2,4(3H)-dione (4a)
Yield 73%; pale yellow powder; mp >300°C; IR: νmax 3374, 3203, 3100, 2932, 1707, 1665, 1659, 1496, 1449, 1397, 1267, 1215, 1151, 1022, 893, 813, 762, 688 cm−1; 1H NMR: δ 11.81 (s, 1H, exchanged with D2O, OH), 11.45 (s, 1H, exchanged with D2O, NH), 10.96 (s, 1H, exchanged with D2O, NH), 10.46 (s, 1H, exchanged with D2O, NH), 7.84 (d, J=7.2 Hz, 1H, Ar), 7.63 (t, J=7.5 Hz, 1H, Ar), 7.50–7.25 (m, 6H, Ar), 7.18 (d, J=6.9 Hz, 1H, Ar); 13C NMR: δ 162.0, 161.8, 159.9, 152.9, 151.5, 140.5, 132.6, 132.19, 129.0, 128.8, 127.2, 126.6, 124.4, 111.7, 116.7, 105.9, 100.1, 99.6. Anal. Calcd for C21H13N3O5: C, 65.12 H, 3.38 N, 10.85. Found: C, 65.21 H, 3.32 N, 10.90.
6-(4-Methylphenyl)-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-2,4(3H)-dione (4b)
Yield 81%; white powder; mp >300°C; IR: νmax 3365, 3207, 3080, 1681, 1624, 1504, 1446, 1392, 1168, 1113, 1019, 974, 891, 765 cm−1; 1H NMR: δ 11.73 (s, 1H, exchanged with D2O, OH), 11.43 (s, 1H, exchanged with D2O, NH), 10.89 (s, 1H, exchanged with D2O, NH), 10.43 (s, 1H, exchanged with D2O, NH), 7.83 (d, J=7.8 Hz, 1H, Ar), 7.63 (t, J=7.2 Hz, 1H, Ar), 7.39 (bd, J=9.0 Hz, 1H, Ar), 7.35 (t, J=7.5 Hz, 1H, Ar), 7.27 (d, J=7.5 Hz, 2H, Ar), 7.09 (d, J=7.5 Hz, 2H, Ar), 2.22 (s, 3H, Me); 13C NMR: δ 163.4, 158.3, 152.9, 152.1, 140.2, 132.7, 132.8, 129.6, 128.9, 128.5, 127.0, 124.3, 124.0, 116.6, 116.5, 106.7, 101.0, 99.2, 21.1. Anal. Calcd for C22H15N3O5: C, 65.83 H, 3.77 N, 10.47. Found: C, 65.88 H, 3.70 N, 10.35.
6-(4-Chlorophenyl)-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-2,4(3H)-dione (4c)
Yield 78%; white powder; mp >300°C; IR: νmax 3405, 3271, 2932, 1700, 1684, 1624, 1505, 1448, 1405, 1249, 1175, 1113, 1028, 763 cm−1; 1H NMR: δ 11.84 (s, 1H, exchanged with D2O, OH), 11.52 (s, 1H, exchanged with D2O, NH), 10.39 (s, 1H, exchanged with D2O, NH), 10.21 (s, 1H, exchanged with D2O, NH), 7.97 (bd, J=8.1 Hz, 3H, Ar), 7.52 (bd, J=8.4 Hz, 3H, Ar), 7.38 (t, J=8.4 Hz, 1H, Ar), 7.37 (t, J=8.7 Hz, 1H, Ar); 13C NMR: δ 162.0, 161.7 158.9, 153.0, 151.5, 140.6, 132.7, 132.2, 129.0, 128.9, 127.2, 126.6, 124.4, 116.7, 116.6, 105.9, 100.1, 99.6. Anal. Calcd for C21H12ClN3O5: C, 59.80 H, 2.87 N, 9.96. Found: C, 59.71 H, 2.73 N, 10.15.
6-(4-Methoxyphenyl)-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-2,4(3H)-dione (4d)
Yield 80%; pale yellow powder; mp >300°C; IR νmax 3432, 3347, 3179, 3073, 2951, 1686, 1624, 1560, 1501, 1452, 1377, 1283, 1226, 1119, 1052, 977, 862, 756 cm−1; 1H NMR: δ 11.68 (s, 1H, exchanged with D2O, OH), 11.42 (s, 1H, exchanged with D2O, NH), 10.88 (s, 1H, exchanged with D2O, NH), 10.42 (s, 1H, exchanged with D2O, NH), 7.84 (d, J=7.8 Hz, 1H, Ar), 7.63 (t, J=7.5 Hz, 1H, Ar), 7.39 (bd, J=9.0 Hz, 1H, Ar), 7.34 (br t, J=9.0 Hz, 1H, Ar), 7.31 (d, J=8.4 Hz, 2H, Ar), 6.87 (d, J=9.0 Hz, 2H, Ar), 3.69 (s, 3H, OMe); 13C NMR: δ 162.1, 161.8, 159.9, 158.7, 153.0, 151.5, 140.2, 132.5, 129.2, 128.0, 124.7, 124.3, 116.6, 114.3, 104.6, 100.1, 99.6, 55.5. Anal. Calcd for C22H15N3O6: C, 63.31 H, 3.62 N, 10.07. Found: C, 63.23 H, 3.71 N, 10.17.
6-(4-Nitrophenyl)-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-2,4(3H)-dione (4e)
Yield 72%; orange powder; mp >300°C; IR: νmax 3419, 3312, 3161, 2226, 1701, 1674, 1599, 1522, 1450, 1397, 1341, 1246, 1109, 977, 837, 761, 702, 545 cm−1; 1H NMR: δ 12.15 (s, 1H, exchanged with D2O, OH), 11.70 (s, 1H, exchanged with D2O, NH), 10.60 (s, 1H, exchanged with D2O, NH), 10.37 (s, 1H, exchanged with D2O, NH), 8.34 (d, J=7.8 Hz, 1H, Ar), 8.13 (t, J=7.5 Hz, 1H, Ar), 7.89 (bd, J=9.0 Hz, 1H, Ar), 7.84 (br t, J=9.0 Hz, 1H, Ar), 7.81 (d, J=8.4 Hz, 2H, Ar), 7.37 (d, J=9.0 Hz, 2H, Ar); 13C-NMR: δ 163.0, 162.1, 161.7, 159.8, 154.0, 153.1, 151.5, 150.3, 150.1, 145.6, 141.6, 140.9, 138.8, 126.8, 126.7, 124.4, 118.8, 116.0, 101.4, 99.0. Anal. Calcd for C21H12N4O7: C, 58.34 H, 2.80 N, 12.96. Found: C, 58.28 H, 2.88 N, 12.85.
6-(4-Fluorophenyl)-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-2,4(3H)-dione (4f)
Yield 71%; pale yellow powder; mp >300°C; IR: νmax 3365, 3198, 3050, 1700, 1671, 1613, 1496, 1449, 1407, 1264, 1214, 1121, 1020, 892, 761, 690 cm−1; 1H NMR: δ 11.82 (s, 1H, exchanged with D2O, OH), 11.52 (s, 1H, exchanged with D2O, NH), 10.96 (s, 1H, exchanged with D2O, NH), 10.47 (s, 1H, exchanged with D2O, NH), 7.84 (d, J=7.2 Hz, 1H, Ar), 7.64 (t, J=7.8 Hz, 1H, Ar), 7.41 (t, J=7.2 Hz, 2H, Ar), 7.33 (d, J=7.5 Hz, 2H, Ar), 7.15 (t, J=8.7 Hz, 2H, Ar); 13C NMR: δ 163.1, 162.0, 161.9, 159.9, 153.0, 151.6, 140.4, 132.6, 128.7, 128.2, 124.4, 116.6, 116.5, 115.9, 115.6, 105.8, 100.2, 99.3. Anal. Calcd for C21H12FN3O5: C, 62.23 H, 2.98 N, 10.37. Found: C, 62.31 H, 2.90 N, 10.29.
6-(3,4-Dimethoxyphenyl)-5-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,7-dihydro-2H-pyrrolo[2,3-d]pyrimidine-2,4(3H)-dione (4g)
Yield 76%; yellow powder; mp >300°C; IR νmax 3526, 3416, 3200, 3058, 1700, 1681, 1608, 1512, 1445, 1261, 1213, 1126, 1018, 918, 761, 714, 603 cm−1; 1H NMR: δ 11.66 (s, 1H, exchanged with D2O, OH), 11.45(s, 1H, exchanged with D2O, NH), 10.94 (s, 1H, exchanged wit D2O, NH), 10.44 (s, 1H, exchanged with D2O, NH), 7.84 (d, J=7.8 Hz, 1H, Ar), 7.63 (t, J=7.5 Hz, 1H, Ar), 7.38 (d, J=8.4 Hz, 1H, Ar), 7.35 (t, J=7.2 Hz, 1H, Ar), 7.02 (s, 1H, Ar), 6.91 (t, J=8.4 Hz, 1H, Ar), 6.89 (t, J=8.7 Hz, 1H, Ar), 3.73 (s, 3H, OMe), 3.69 (s, 3H, OMe); 13C NMR: δ 162.1, 161.9, 159.9, 152.9, 151.6, 148.7, 148.2, 140.1, 129.1, 124.8, 124.3, 119.1, 116.6, 112.3, 110.7, 104.9, 100.2, 99.8, 55.9, 55.6. Anal. Calcd for C23H17N3O7: C, 61.75 H, 3.83 N, 9.39. Found: C, 61.80 H, 3.86 N, 9.31.
6-(Phenyl)-7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,3-dimethyl-1,5-dihydro-2H-pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione (4h)
Yield 77%; pale yellow powder; mp >300°C [22].
6-(4-Methylphenyl)-7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,3-dimethyl-1,5-dihydro-2H-pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione (4i)
Yield 86%; pale yellow powder; mp >300°C; IR: νmax 3427, 3197, 3047, 2949, 1687, 1648, 1552, 1500, 1447, 1387, 1280, 1221, 1150, 978, 895, 833, 760, 688 cm−1; 1H NMR: δ 11.76 (s, 1H, exchanged with D2O, OH), 11.53 (s, 1H, exchanged with D2O, 1H of NH), 7.84 (d, J=8.1 Hz, 1H, Ar), 7.64 (t, J=8.7 Hz, 1H, Ar), 7.38 (t, J=8.7 Hz, 2H, Ar), 7.34 (d, J=7.5 Hz, 2H, Ar), 7.15 (d, J=7.8 Hz, 2H, Ar), 3.53 (s, 3H, 3-Me), 3.16 (s, 3H, 1-Me), 2.27 (s, 3H, Me); 13C NMR: δ 163.1, 157.1, 157.0, 153.4, 153.3, 151.6, 151.0, 145.4, 144.0, 141.2, 137.5, 132.6, 128.2, 126.6, 126.5, 124.2, 123.8, 115.9, 100.9, 31.2, 26.8, 21.2. Anal. Calcd for C24H19N3O5: C, 67.13 H, 4.46 N, 9.79. Found: C, 67.05 H, 4.50 N, 9.84.
6-(4-Chlorophenyl)-7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,3-dimethyl-1,5-dihydro-2H-pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione (4j)
Yield 80%; pale yellow powder; mp >300°C; IR: νmax 3452, 3361, 3188, 2954, 1695, 1649, 1608, 1554, 1449, 1389, 1272, 1237, 1164, 1059, 976, 895, 765, cm−1; 1H NMR: δ 11.84 (s, 1H, exchanged with D2O, OH), 11.64 (s, 1H, exchanged with D2O, NH), 7.86 (d, J=7.2 Hz, 1H, Ar), 7.64 (t, J=7.5 Hz, 1H, Ar), 7.55‒7.25 (m, 6H, Ar), 3.50 (s, 3H, 3-Me), 3.31 (s, 3H, 1-Me); 13C NMR: δ 161.1, 158.3, 153.0, 151.6, 151.1, 132.7, 132.0, 131.5, 130.8, 128.9, 128.6, 128.5, 128.4, 124.3, 124.1, 116.6, 100.1, 96.3, 31.0, 28.1. Anal. Calcd for C23H16ClN3O5: C, 61.41 H, 3.59 N, 9.34. Found: C, 61.33 H, 3.45 N, 9.42.
6-(4-Methoxyphenyl)-7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,3-dimethyl-1,5-dihydro-2H-pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione (4k)
Yield 84%; pale yellow powder; mp >300°C (Lit. [22]: yield 93%, white solid, mp 391–393°C).
6-(4-Nitrophenyl)-7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,3-dimethyl-1,5-dihydro-2H-pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione (4l)
Yield 75%; orange powder; mp >300°C; IR: νmax 3427, 3149, 3057, 2944, 2241, 1690, 1678, 1642, 1561, 1484, 1277, 1098, 1021, 975, 844, 742, 628 cm−1; 1H NMR: δ 12.03 (bs, 1H, exchanged with D2O, OH), 11.73 (s, 1H, exchanged with D2O, NH), 8.08 (t, J=8.1 Hz, 2H, Ar), 7.91 (t, J=7.8 Hz, 1H, Ar), 7.80–7.50 (m, 4H, Ar), 7.41 (d, J=8.1 Hz, 1H, Ar), 7.36 (t, J=7.8 Hz, 1H, Ar), 3.49 (s, 3H, 3-Me), 3.22 (s, 3H, 1-Me); 13C NMR: δ 162.1, 158.2, 158.0, 153.4, 153.3, 151.6, 151.0, 145.4, 144.9, 141.2, 138.6, 132.6, 127.2, 126.7, 126.4, 124.1, 123.8, 116.6, 110.9, 31.1, 27.8. Anal. Calcd for C23H16N4O7: C, 60.00 H, 3.50 N, 12.17. Found: C, 59.95 H, 3.57 N, 12.26.
6-(4-Fluorophenyl)-7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,3-dimethyl-1,5-dihydro-2H-pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione (4m)
Yield 74%; white powder; mp 272–274°C (Lit. [22]: yield 92%; white solid, mp 268–270°C).
6-(3,4-Dimethoxyphenyl)-7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-1,3-dimethyl-1,5-dihydro-2H-pyrrolo[3,2-d]pyrimidine-2,4(3H)-dione (4n)
Yield 79%; pale yellow powder; mp >300°C; IR: νmax 3376, 3198, 2980, 1702, 1683, 1619, 1503, 1440, 1219, 1122, 1027, 976, 829, 758, 676 cm−1; 1H NMR: δ 11.73 (s, 1H, exchanged with D2O, OH), 10.98 (s, 1H, exchanged with D2O, NH), 7.86 (d, J=7.8 Hz, 1H, Ar), 7.64 (t, J=7.5 Hz, 1H, Ar), 7.41 (d, J=7.5 Hz, 1H, Ar), 7.35 (t, J=7.8 Hz, 1H, Ar), 7.05 (s, 1H, Ar), 7.00 (d, J=8.4 Hz, 1H, Ar), 6.93 (d, J=8.4 Hz, 1H, Ar), 3.71 (s, 3H, MeO), 3.64 (s, 3H, MeO), 3.57 (s, 3H, 3-Me), 3.17 (s, 3H, 1-Me); 13C NMR: δ 162.2, 162.0, 158.4, 153.3, 153.0, 151.1, 148.7, 148.6, 139.9, 132.6, 129.9, 125.0, 124.5, 119.7, 116.5, 112.3, 111.1, 105.7, 100.0, 99.7, 55.9, 55.6, 31.2, 27.8. Anal. Calcd for C25H21N3O7: C, 63.16 H, 4.45 N, 8.84. Found: C, 63.08 H, 4.54 N, 8.75.
Acknowledgments
We are grateful to Urmia University for the financial support. We also thank Professor R.H. Prager from Flinders University, Australia, for proofreading and language editing of the manuscript.
References
[1] Ryota, M.; Keisuke, A.; Seijiro, M. Asymmetric indoline synthesis via intramolecular Aza-Michael addition mediated by bifunctional organocatalysts. Org. Lett. 2013, 15, 3658–3661.10.1021/ol401538bSearch in Google Scholar PubMed
[2] Emmadi, N. R.; Atmakur, K.; Bingi, C.; Godumagadda, N. R.; Kumar, C. G.; Nanubolu, J. B. Regioselective synthesis of 3-benzyl substituted pyrimidino chromen-2-ones and evaluation of anti-microbial and anti-biofilm activities. Bioorg. Med. Chem. Lett. 2014, 24, 485–489.10.1016/j.bmcl.2013.12.038Search in Google Scholar PubMed
[3] Paengsri, W.; Lee, V. S.; Chong, W. L.; Wahab, H. A.; Baramee, A. Synthesis, antituberculosis activity and molecular docking studies for novel naphthoquinone derivatives. Int. J. Biol. Chem. 2012, 6, 69–88.10.3923/ijbc.2012.69.88Search in Google Scholar
[4] Rosowsky, A.; Mota, C. E.; Queener, S. F. Synthesis and antifolate activity of 2,4-diamino-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine analogues of trimetrexate and piritrexim. J. Heterocycl. Chem. 1995, 32, 335–340.10.1002/jhet.5570320155Search in Google Scholar
[5] Deyanov, A. B.; Niyazov, R. K.; Nazmetdinov, F. Y.; Syropyatov, B. Y.; Kolla, V. E.; Konshin, M. E. Amides, nitriles of 2-arylamino-5-carboxy(carbethoxy)-6-methylnicotinic acids and 1-aryl-6-carbethoxy-7-methyl-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidines – synthesis and biological activity. Khim.-Farm. Zh. 1991, 25, 26–28.Search in Google Scholar
[6] Satti, N. K.; Suri, K. A.; Sun, O. P.; Kapil, A. Synthesis and antileishmanial activity of some pyrido[1,2-a]pyrimidines and phenanthrolines. Indian J. Chem. Sect. B. 1993, 32B, 978–980.Search in Google Scholar
[7] Kolla, V. E.; Deyanov, A. B.; Nazmetdinov, F. Y.; Kashina, Z. N.; Drovosekova, L. P. Examining the anti-inflammatory and analgesic activity of 2-substituted 1-aryl-6-carboxy(carboethoxy)-7-methyl-4-oxo-1,4-dihydro pyrido[2,3-d] pyrimidines. Khim.-Farm. Zh. 1993, 27, 29–33.Search in Google Scholar
[8] Saladowska, H.; Bartoszko-Malik, A.; Zawisza, T. Synthesis and properties of new derivatives of ethyl 7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylate. Farmaco1990, 45, 101–110.10.1002/chin.199037219Search in Google Scholar PubMed
[9] Nasr, M. N.; Gineinah, M. M. Pyrido[2,3-d]pyrimidines and pyrimido[5′,4′:5,6]pyrido[2,3-d]pyrimidines as new antiviral agents: synthesis and biological activity. Arch. Pharm. 2002, 6, 289–295.10.1002/chin.200250118Search in Google Scholar
[10] Jung, J. C.; Jung, Y. J.; Park, O. S. Synthetic approaches and biological activities of 4-hydroxycoumarin derivatives. Molecules2009, 14, 4790–4803.10.3390/molecules14114790Search in Google Scholar
[11] Berghot, M. A.; Kandeel, E. M.; Abdel-Rahman, A. H.; Abdel-Motaal, M. Synthesis, antioxidant and cytotoxic activities of novel naphthoquinone derivatives from 2,3-dihydro-2,3-epoxy-1,4- naphthoquinone. Med. Chem. 2014, 4, 381–388.Search in Google Scholar
[12] Tangmouo, J. G.; Meli, A. L.; Komguem, J.; Kuete, V.; Ngounou, F. N.; Lontsi, D.; Beng, V. P.; Choudhary, M. I.; Sondengam, B. L. Crassiflorone, a new naphthoquinone from Diospyros crassiflora. Tetrahedron Lett.2006, 47, 3067–3069.10.1016/j.tetlet.2006.03.006Search in Google Scholar
[13] Siddiqui, I. R.; Shamin, S.; Singh, A.; Srivastava, V.; Yadav, S. Moisture compatible and recyclable indium (III) chloride catalyzed and microwave assisted efficient route to substituted 1H-quinolin-2-ones. Arkivoc2010, 11, 232–241.10.3998/ark.5550190.0011.b19Search in Google Scholar
[14] Desai, J. T.; Desai, C. K.; Desai, K. R. A convenient, rapid and eco-friendly synthesis of isoxazoline heterocyclic moiety containing bridge at 2°-amine as potential pharmacological agent. J. Iran. Chem. Soc. 2008, 5, 67–73.10.1007/BF03245817Search in Google Scholar
[15] Khalafy, J.; Etivand, N.; Dilmaghani, S.; Ezzati, M.; Poursattar Marjani, A. A convenient and mild synthesis of new 2-aryl-3-hydroxy-6,7-dihydro-1H-indol-4(5H)-ones via a one-pot, three-component reaction in water. Tetrahedron Lett. 2014, 55, 3781–3783.10.1016/j.tetlet.2014.05.073Search in Google Scholar
[16] Khalafy, J.; Ezzati, M.; Rimaz, M.; Poursattar Marjani, A.; Yaghoobnejad Asl, H. An efficient and facile regioselective synthesis of new substituted (E)-1-(3-aryl-7,8-dihydrocinnoline-5(6H)-ylidene)hydrazines and (1E,2E)-1,2-bis(3-aryl-7,8-dihydrocinnoline-5(6H)-ylidene)hydrazines. J. Iran. Chem. Soc.2014, 11, 1067–1074.10.1007/s13738-013-0378-2Search in Google Scholar
[17] Poursattar Marjani, A.; Khadafy, J.; Mahmoudi, S. A simple one-pot synthesis of new 9-aroyl-3,4,6,7,9,10-hexahydro-1,8(2H,5H)-acridinediones. Arkivoc2016, iii, 262–260.10.3998/ark.5550190.p009.445Search in Google Scholar
[18] Khalafy, J.; Badparvar, F.; Poursattar Marjani, A. Synthesis of 1-aryl-6,6-dimethyl-2-phenyl-6,7-dihydro-1H-indol-4(5H)-ones by two steps, in a three-component reaction. J. Chil. Chem. Soc.2016, 61, 3112–3115.10.4067/S0717-97072016000300021Search in Google Scholar
[19] Poursattar Marjani, A.; Khalafy, J.; Chitan, M.; Mahmoodi, S. Microwave-assisted synthesis of acridine-1,8(2H,5H)-diones via a one-pot, three-component reaction. Iran. J. Chem. Chem. Eng.2017, 36, 1–6.Search in Google Scholar
[20] Javahershenas, R.; Khalafy, J. A green synthesis of 7-amino-5-(4-aroyl)-1,3-dimethyl-2,4-dioxo-1,2,3,4,5,8-hexahydropyrido[2,3-d]pyrimidine-6-carbonitrile derivatives by a one-pot, three component reaction. J. Heterocycl. Chem. 2017, 54, 3163–3168.10.1002/jhet.2930Search in Google Scholar
[21] Bharti, R.; Parvin, T. Molecular diversity from the L-proline catalyzed, three-component reactions of 4-hydroxycoumarin, aldehyde, and 3-aminopyrazole or 1,3-dimethyl-6-aminouracil. Synth. Commun. 2015, 45, 1442–1450.10.1080/00397911.2015.1023900Search in Google Scholar
[22] Mishra, R.; Panday, A. K.; Choudhury, L. H.; Pal, J.; Subramanian, R.; Verma, A. Multicomponent reactions of arylglyoxal, 4-hydroxycoumarin, and cyclic 1,3-c,n-binucleophiles: binucleophile-directed synthesis of fused five- and six-membered n-heterocycles. Eup. J. Org. Chem. 2017, 2017, 2789–2800.10.1002/ejoc.201700115Search in Google Scholar
[23] Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals; Pergamon Press: Oxford, 1988.Search in Google Scholar
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