Introduction

The synthesis of nitrogen-containing heterocycles is still the backbone of new pharmaceuticals. A famous representative is quinine. Its synthesis and derivatives thereof are still an inspiration for organic chemists [1,2,3,4]. The tricyclic system of pyrrolo[3,4-b]quinoline is a further interesting source object for construction of new bioactive structures. The nucleus of this system can be found in the natural alkaloids camptothecin [5] and luotonin A [6], while a wide spectrum of pharmaceutical activities (antitumor [7, 8], antibacterial [9], and interferon inducing [10]) is reported for its derivatives. Besides, acetylcholinesterase inhibitor [11] and KATP openers [12] have been found among these derivatives as well as some other compounds with the ability to bind benzodiazepine receptors [13, 14], inhibitors of PI3-kinase [15], phosphodiesterase inhibitor [16], PDE-V inhibitors active in the treatment of erectile disfunction [17], and modulators of γ-aminobutyric acid (GABA)a receptors [18].

β-Enamino imides are known as interesting two-center enamine-type reagents, being of highly interest for the three- and tetra-component reactions of cyclocondensation [19,20,21,22]. Also, there are many publications reporting the use of dimedone in the multicomponent reactions with various enamines [23,24,25,26,27,28,29].

During the last decades, using ultrasounds irradiation (sonochemistry), as a nonconventional method of work in chemistry, became a versatile tool in a large variety of syntheses, because of its numerous advantages resulting in higher yields, shorter reaction times and milder reactions conditions [30,31,32,33,34,35,36,37]. Taking into consideration our experience in the field of multicomponent reactions [23] as well as that one in the area of sonochemistry [33,34,35,36,37], we decide to synthesize new pyrrolo[3,4-b]quinolines via catalyzed one-pot three-component reactions, both under conventional thermal heating and ultrasounds irradiation.

Results and discussion

In accordance with our goal, we have proposed a new effective approach for the synthesis of the polyfunctional pyrroloquinolines 4, by the one-pot three-component cyclocondensation of aromatic aldehydes 1, dimedone (2), and β-enamino imides 3, catalyzed by trifluoroacetic acid. The reactions were carried out in toluene, both under conventional thermal heating (70 °C) or using ultrasounds irradiation (room temperature) (Scheme 1).

scheme 1

A model reaction between 4-fluorobenzaldehyde (1a) with dimedone (2) and 1-benzyl-3-(4-methylaniline)-1H-pyrrole-2,5-dione (3a) has been initially investigated to optimize the reaction conditions. It has been found that a complex mixture of the reaction products is formed in this reaction running in ethanol with l-proline [19] and DABCO. The product 4a can be extracted from the mixture with a yield of 10% (l-proline) and a yield of 6% (DABCO). If a solution of trifluoroacetic acid in dichloromethane is used as a catalyst, the target product yield reaches 61% after 6 h of boiling. Then, other solvents such as acetonitrile, dichloroethane, acetic acid, and toluene were tested for their catalytic efficiency at heating to various temperatures with trifluoroacetic acid and the highest efficiency has been registered for the toluene mixture (see Table 1). Besides, the highest yield of the cyclocondensation product can be reached using the equimolar amount of trifluoroacetic acid after 2 h of heating to 70 °C.

Table 1 Optimization of reaction conditions 4a
Full size table

As we may notice from Table 1, under conventional thermal heating the reaction pathways had some major disadvantages, including low to moderate yields, long reaction time, high energy consumption, and considerable amounts of solvents. For these reasons, we decided to use ultrasounds irradiation, as nonconventional methods, for the synthesis (Scheme 1). It has been found that the reaction does not run in dichloromethane, dichloroethane, and toluene if no trifluoroacetic acid was added. However, introduction of the equimolar amount of the acid leads to shorter reaction time (less than 5 min) and higher yields (from 58 to 64% for dichloroethane; 61 to 69% for dichloromethane, and 83 to 90% for toluene; see Tables 1 and 2). Also, in the case of the reactions running up in toluene with trifluoroacetic acid as catalyst, the yields were rising with the time, reaching 78, 90, and 90% for the reaction times 3, 5, and 10 min, respectively. Therefore, 5 min is the most optimal reaction time (see Table 2, entries 6–8).

Table 2 Optimization of reaction conditions 4a under ultrasounds irradiation
Full size table

A possible mechanism of formation for the derivatives of pyrroloquinoline 4 is shown in Scheme 2. Activation of β-enamino imides 3 takes place in the presence of trifluoroacetic acid forming the Enol A2. In parallel, the aromatic aldehyde 1 and dimedone undergo a condensation reaction forming the Michael acceptor B. In the following condensation, A2 and B form the Michael adduct C. Finally, in a third condensation, this Michael adduct undergoes intramolecular cyclocondensation forming the pyrroloquinoline nucleus 4.

scheme 2

Table 3 lists a comparative study for the synthesis of pyrroloquinoline derivatives 4a–4j via catalyzed one-pot three-component reactions, under thermal heating and ultrasounds irradiation. We may notice that under ultrasounds irradiation, the reaction time decreases significantly (from 2 h to 5 min) and, in some cases, the yields are much better (for instance, with 14% higher for the reaction product 4d). It has been found that the reaction yield rises with increasing the aldehydes electrophilicity under conventional thermal heating conditions (4d: 54%, 4c: 56%, 4e: 69%), while under ultrasounds irradiation no significant differences were found.

Table 3 Comparative data concerning synthesis of pyrrolo[3,4-b]quinolines 4a–4j under conventional thermal heating and ultrasounds irradiation
Full size table

In continuing of our studies, we found that some other 1,3-dicarbonyl products, such as 1,3-cyclohexanedione and barbituric acid, can be used in analogous one-pot three-component reactions. Thus, 1,3-cyclohexanedione reacts like dimedone under optimized conditions forming pyrroloquinoline 5 (in moderate yields, 67% for thermal heating and 64% for ultrasounds irradiation). Also, the less CH-acid barbituric acid could be used instead of dimedone. Under the same conditions, a prolonging of the reaction times is observed (either 6 h of thermal heating either 20 min of ultrasounds irradiation). The yields of the desired pyrrolo[3′,4′:5,6]pyrido[2,3-d]pyrimidine 6 are still high (74% for thermal heating and 72% for ultrasounds irradiation, see Scheme 3).

scheme 3

In conclusion, we present herein a general, straight, and efficient method for the synthesis of pyrrolo[3,4-b]quinolines under conventional thermal heating and ultrasounds irradiation. The reactions pathway involve a one-pot three-component reactions of β-enamino imides, aromatic aldehydes, and 1,3-diketone catalyzed by trifluoroacetic acid. It is shown that under ultrasounds irradiation, the reaction time decreases significantly (from hours to minutes) and, in some cases, the yields are much better.

Experimental

All melting points were determined on an MEL-TEMP II apparatus in open capillary tubes. IR data were recorded as films on KBr pellets on a FT-IR Shimadzu Prestige 8400 s spectrophotometer. The NMR measurements were carried out on a Bruker Avance III 500 MHz spectrometer with 1H and 13C frequencies of 500 and 125 MHz, respectively. HPLC/MS was carried out on a system consisting of an Agilent 1100 Series high-pressure liquid chromatography equipped with a diode matrix and Agilent LC/MSD SL mass-selective detector. HPLC/MS parameters: column: Zorbax SB-C18, 1.8 µ, 4.6 × 30 mm; ionization method: chemical ionization under atmospheric pressure; ionization mode: simultaneous scanning of positive and negative ions in m/z range 100–650. Microanalyses were performed with Euro EA 3000 Elemental Analyzer. Ultrasound-assisted reactions were carried out using reactor: Sonics (Sonics VCX-130, USA), with a nominal power of 130 W, frequency 20 kHz, the titanium standard probe tip (diameter 6 mm; length 116 mm), was fixed tightly to the ultrasounds converter and was immersed in the used solvent. Analytical thin-layer chromatography was performed with commercial silica gel plates 60 F254 (Merck) and visualized with UV light.

β-Enamino imides (3) were synthesized by the method [38]. All chemicals used in this study were commercially available and used without further purification.

General procedure

A solution of β-enamino imide (0.4 mmol), aromatic aldehyde (0.4 mmol), dimedone (0.4 mmol), and trifluoroacetic acid (0.4 mmol) in 5 cm3 toluene was stirred at 70 °C for 2 h while checking the reaction progress by TLC. After completion, the reaction mass was concentrated under vacuum and the crude product was purified by column chromatography (CH2Cl2/MeOH, 99:1) to provide the analytically pure product.

Ultrasound-assisted reaction A solution of β-enamino imide (0.4 mmol), aromatic aldehyde (0.4 mmol), dimedone (0.4 mmol), and trifluoroacetic acid (0.4 mmol) in 15 cm3 toluene was exposed to US irradiation for 5 min (best results were obtained applying a pulse irradiation—5 s pulse/5 s pause, 100% from the full power of the generator). After completion, the reaction mass was concentrated under vacuum and the crude product was purified by column chromatography (CH2Cl2/MeOH, 99:1) to provide the analytically pure product.

2-Benzyl-9-(4-fluorophenyl)-6,6-dimethyl-4-(4-methylphenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4a, C33H29FN2O3)

Yellow solid; yield: 83% using CH (conventional heating), 90% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.48; m.p.: 196–198 °C; 1H NMR (500 MHz, CDCl3): δ = 0.89 (s, 3H, CH3), 0.98 (s, 3H, CH3), 2.05 (d, 1H, J = 17.5 Hz, CH2), 2.11 (d, 1H, J = 17.5 Hz, CH2), 2.18 (d, 1H, J = 16.0 Hz, CH2), 2.20 (d, 1H, J = 16.0 Hz, CH2), 2.47 (s, 3H, CH3), 4.45 (s, 2H, CH2), 5.13 (s, 1H, CH9), 6.98–7.02 (m, 2H, Ar), 7.14 (d, 2H, J = 8.0 Hz, Ar), 7.23–7.37 (m, 9H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 21.5, 27.1, 29.4, 32.4, 33.4, 40.6, 41.3, 50.3, 113.8, 114.8, 115.4, 115.6, 119.9, 127.8, 128.6, 128.7, 129.5, 129.6, 129.9, 130.5, 134.6, 136.5, 137.5, 139.9, 140.4, 151.6, 160.9, 162.8, 163.8, 168.6, 195.9 ppm; IR (KBr): \( \bar{\nu } \) = 3444, 2960, 2872, 1766, 1714, 1664, 1643, 1572, 1508, 1429, 1361, 1257, 1219, 1155, 1097, 1018, 927, 837, 744, 698 cm−1; HPLC/MS: m/z = 520 (M+).

2-Benzyl-9-(4-chlorophenyl)-6,6-dimethyl-4-(4-methylphenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4b, C33H29ClN2O3)

Yellow solid; yield: 77% using CH (conventional heating), 80% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.46; m.p.: 142–144 °C; 1H NMR (500 MHz, CDCl3): δ = 0.89 (s, 3H, CH3), 0.98 (s, 3H, CH3), 2.04 (d, 1H, J = 17.0 Hz, CH2), 2.11 (d, 1H, J = 17.0 Hz, CH2), 2.18 (d, 1H, J = 16.5 Hz, CH2), 2.20 (d, 1H, J = 16.5 Hz, CH2), 2.47 (s, 3H, CH3), 4.45 (s, 2H, CH2), 5.12 (s, 1H, CH9), 7.13 (d, 2H, J = 8.0 Hz, Ar), 7.18 (d, 2H, J = 8.0 Hz, Ar), 7.23–7.34 (m, 9H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 21.5, 27.2, 29.4, 32.4, 33.7, 40.6, 41.4, 50.3, 113.6, 114.5, 125.4, 127.8, 128.3, 128.7, 128.7, 128.9, 129.1, 129.4, 130.5, 132.8, 134.6, 136.5, 137.6, 139.9, 143.1, 151.7, 163.8, 168.5, 195.8 ppm; IR (KBr): \( \bar{\nu } \) = 3464, 2956, 2872, 1768, 1712, 1668, 1641, 1572, 1512,1429, 1365, 1295, 1220, 1153, 1064, 1014, 835, 744 cm−1; HPLC/MS: m/z = 537 (M+).

2-Benzyl-4-(4-bromophenyl)-6,6-dimethyl-9-phenyl-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4c, C32H27BrN2O3)

Yellow solid; yield: 56% using CH (conventional heating), 69% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.50; m.p.: 213–215 °C; 1H NMR (500 MHz, CDCl3): δ = 0.91 (s, 3H, CH3), 0.99 (s, 3H, CH3), 2.02 (d, 1H, J = 17.0 Hz, CH2), 2.09 (d, 1H, J = 17.0 Hz, CH2), 2.19 (d, 1H, J = 16.5 Hz, CH2), 2.20 (d, 1H, J = 16.5 Hz, CH2), 4.44 (m, 2H, CH2), 5.14 (s, 1H, CH9), 7.17 (d, 2H, J = 8.5 Hz, Ar), 7.23–7.30 (m, 6H, Ar), 7.33 (d, 2H, J = 7.5 Hz, Ar), 7.37 (d, 2H, J = 7.5 Hz, Ar), 7.64 (d, 2H, J = 8.5 Hz, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 27.2, 29.4, 32.5, 34.0, 40.7, 41.4, 50.3, 114.2, 115.5, 123.9, 127.2, 127.8, 128.0, 128.7, 128.7, 128.8, 130.7, 133.1, 136.4, 136.4, 137.0, 144.2, 150.7, 163.9, 168.4, 195.7 ppm; IR (KBr): \( \bar{\nu } \) = 3445, 2958, 2872, 1766, 1710, 1668, 1575, 1491, 1429, 1361, 1261, 1147, 1072, 1012, 945, 842, 734, 696 cm−1; HPLC/MS: m/z = 566 (M+).

2-Benzyl-4-(4-bromophenyl)-6,6-dimethyl-9-(4-methylphenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4d, C32H29BrN2O3)

Yellow solid; yield: 54% using CH (conventional heating), 68% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.39; m.p.: 105–107 °C; 1H NMR (500 MHz, CDCl3): δ = 0.92 (s, 3H, CH3), 0.99 (s, 3H, CH3), 2.03 (d, 1H, J = 17.5 Hz, CH2), 2.09 (d, 1H, J = 17.5 Hz, CH2), 2.19 (d, 1H, J = 16.5 Hz, CH2), 2.20 (d, 1H, J = 16.5 Hz, CH2), 2.30 (s, 3H, CH3), 4.43 (m, 2H, CH2), 5.10 (s, 1H, CH9), 7.12–7.17 (m, 4H, Ar), 7.24-7.34 (m, 7H, Ar), 7.65 (d, 2H, J = 8.5 Hz, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 21.2, 27.2, 29.4, 32.4, 33.6, 40.7, 41.3, 50.2, 114.2, 115.7, 123.8, 127.8, 127.8, 128.6, 128.6, 128.7, 129.5, 130.7, 133.1, 136.4, 136.4, 136.8, 136.8, 141.3, 150.6, 163.9, 168.4, 195.8 ppm; IR (KBr): \( \bar{\nu } \) = 3445, 2956, 2870, 1766, 1712, 1670, 1573, 1489, 1363, 1259, 1145, 1066, 1012, 943, 842, 744, 700 cm−1; HPLC/MS: m/z = 580 (M+).

2-Benzyl-4-(4-bromophenyl)-6,6-dimethyl-9-(4-nitrophenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4e, C32H26BrN3O5)

Yellow solid; yield: 69% using CH (conventional heating), 72% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.48; m.p.: 136–138 °C;1H NMR (500 MHz, CDCl3): δ = 0.92 (s, 3H, CH3), 1.00 (s, 3H, CH3), 2.05 (d, 1H, J = 17.5 Hz, CH2), 2.11 (d, 1H, J = 17.5 Hz, CH2), 2.19 (d, 1H, J = 16.5 Hz, CH2), 2.22 (d, 1H, J = 16.5 Hz, CH2), 4.45 (s, 2H, CH2), 5.24 (s, 1H, CH9), 7.16 (d, 2H, J = 8.0 Hz, Ar), 7.24 (m, 5H, Ar), 7.56 (d, 2H, J = 8.5 Hz, Ar), 7.67 (d, 2H, J = 8.0 Hz, Ar), 8.20 (d, 2H, J = 8.5 Hz, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 27.2, 29.8, 32.5, 33.6, 40.7, 41.5, 50.1, 113.3, 113.9, 124.1, 124.2, 128.0, 128.8, 128.8, 129.0, 130.6, 133.3, 135.9, 136.1, 136.6, 147.0, 151.0, 151.6, 163.4, 168.1, 195.6 ppm; IR (KBr): \( \bar{\nu } \) = 3445, 2960, 2872, 1766, 1714, 1668, 1643, 1575, 1508, 1429, 1361, 1257, 1155, 1097, 1018, 927, 837, 744, 696 cm−1; HPLC/MS: m/z = 611 (M+).

9-(4-Chlorophenyl)-2,6,6-trimethyl-4-(4-methylphenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4f, C27H25ClN2O3)

Yellow solid; yield: 65% using CH (conventional heating), 71% using US (ultrasounds irradiation); TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.45; m.p.: 193–195 °C; 1H NMR (500 MHz, CDCl3): δ = 0.91 (s, 3H, CH3), 0.99 (s, 3H, CH3), 2.07 (d, 1H, J = 17.5 Hz, CH2), 2.13 (d, 1H, J = 17.5 Hz, CH2), 2.18 (d, 1H, J = 16.5 Hz, CH2), 2.21 (d, 1H, J = 16.5 Hz, CH2), 2.47 (s, 3H, CH3), 2.80 (s, 3H, CH3), 5.12 (s, 1H, CH9), 7.14 (d, 2H, J = 8.0 Hz, Ar), 7.28 (m, 2H, Ar), 7.34 (m, 4H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 21.5, 23.4, 27.1, 29.4, 32.4, 33.6, 40.6, 50.3, 113.5, 114.5, 128.6, 128.8, 129.4, 130.5, 132.8, 134.6, 137.6, 140.0, 143.1, 151.7, 164.3, 168.8, 195.8 ppm; IR (KBr): \( \bar{\nu } \) = 3435, 2955, 2891, 1765, 1714, 1670, 1641, 1573, 1512, 1438, 1363, 1244, 1149, 1089, 972, 835, 748 cm−1; HPLC/MS: m/z = 460 (M+).

2,6,6-Trimethyl-4-(4-methylphenyl)-9-(3-nitrophenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4 g, C27H25N3O5)

Yellow solid; yield: 77% using CH (conventional heating), 83% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.41; m.p.: 208–209 °C; 1H NMR (500 MHz, CDCl3): δ = 0.92 (s, 3H, CH3), 1.01 (s, 3H, CH3), 2.13 (d, 1H, J = 17.5 Hz, CH2), 2.17 (d, 1H, J = 17.5 Hz, CH2), 2.20 (d, 1H, J = 16.5 Hz, CH2), 2.24 (d, 1H, J = 16.5 Hz, CH2), 2.48 (s, 3H, CH3), 2.81 (s, 3H, CH3), 5.27 (s, 1H, CH9), 7.18 (d, 2H, J = 7.5 Hz, Ar), 7.35 (d, 2H, J = 8.0 Hz, Ar), 7.50 (d, 1H, J = 8.0 Hz, Ar), 7.88 (d, 1H, J = 7.7 Hz, Ar), 8.07 (d, 1H, J = 8.2 Hz, Ar), 8.18 (s, 1H, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 21.5, 23.5, 27.1, 29.4, 32.5, 34.1, 40.6, 50.2, 113.1, 113.8, 122.2, 122.6, 129.4, 130.7, 134.4, 134.7, 138.1, 140.2, 146.6, 148.8, 152.6, 164.0, 168.7, 195.8 ppm; IR (KBr): \( \bar{\nu } \) = 3444, 2956, 2868, 1768, 1710, 1670, 1645, 1577, 1529, 1438, 1365, 1344, 1246, 1151, 1103, 1035, 981, 827, 732, 688 cm−1; HPLC/MS: m/z = 471 (M+).

4-(4-Bromophenyl)-9-(4-chlorophenyl)-2,6,6-trimethyl-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4 h, C26H22BrClN2O3)

Yellow solid; yield: 72% using CH (conventional heating), 73% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.48; m.p.: 216–218 °C; 1H NMR (500 MHz, CDCl3): δ = 0.94 (s, 3H, CH3), 1.03 (s, 3H, CH3), 2.07 (d, 1H, J = 17.5 Hz, CH2), 2.14 (d, 1H, J = 17.5 Hz, CH2), 2.22 (d, 1H, J = 16.5 Hz, CH2), 2.25 (d, 1H, J = 16.5 Hz, CH2), 2.84 (s, 3H, CH3), 5.14 (s, 1H, CH9), 7.19 (d, 2H, J = 8.5 Hz, Ar), 7.29-7.35 (m, 4H, Ar), 7.70 (d, 2H, J = 8.5 Hz, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 23.5, 27.4, 29.4, 32.5, 33.7, 40.7, 50.2, 113.9, 115.1, 124.0, 128.9, 129.4, 130.6, 133.0, 133.2, 136.3, 137.2, 142.8, 150.9, 164.2, 168.6, 195.7 ppm; IR (KBr): \( \bar{\nu } \) = 3462, 2959, 2874, 1770, 1710, 1672, 1643, 1575, 1489, 1438, 1363, 1246, 1151, 1091, 1031, 981, 835, 748 cm−1; HPLC/MS: m/z = 524 (M+).

4-(4-Bromophenyl)-2,6,6-trimethyl-9-(3-nitrophenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4i, C26H22BrN3O5)

Yellow solid; yield: 80% using CH (conventional heating), 85% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.38; m.p.: 221–223 °C; 1H NMR (500 MHz, CDCl3): δ = 0.93 (s, 3H, CH3), 1.02 (s, 3H, CH3), 2.10 (d, 1H, J = 17.5 Hz, CH2), 2.15 (d, 1H, J = 17.5 Hz, CH2), 2.20 (d, 1H, J = 16.5 Hz, CH2), 2.24 (d, 1H, J = 16.5 Hz, CH2), 2.82 (s, 3H, CH3), 5.26 (s, 1H, CH9), 7.20 (d, 2H, J = 8.5 Hz, Ar), 7.51 (t, 1H, J = 8.0 Hz, Ar), 7.69 (d, 2H, J = 8.5 Hz, Ar), 7.88 (d, 1H, J = 7.7 Hz, Ar), 8.07 (d, 1H, J = 7.5 Hz, Ar), 8.15 (t, 1H, J = 2.0 Hz, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 23.6, 27.1, 29.4, 32.6, 34.1, 40.7, 50.2, 113.4, 114.3, 122.3, 122.5, 124.2, 129.5, 130.6, 133.3, 134.7, 136.0, 137.6, 146.3, 148.8, 151.8, 163.9, 168.5, 195.7 ppm; IR (KBr): \( \bar{\nu } \) = 3444, 2960, 2870, 1768, 1707, 1674, 1645, 1577, 1533, 1491, 1442, 1363, 1246, 1147, 1066, 1031, 983, 846, 734, 694 cm−1; HPLC/MS: m/z = 535 (M+).

4-(4-Bromophenyl)-2,6,6-trimethyl-9-(4-nitrophenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (4j, C26H22BrN3O5)

Yellow solid; yield: 79% using CH (conventional heating), 79% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.45; m.p.: 204–205 °C; 1H NMR (500 MHz, CDCl3): δ = 0.93 (s, 3H, CH3), 1.02 (s, 3H, CH3), 2.08 (d, 1H, J = 17.5 Hz, CH2), 2.14 (d, 1H, J = 17.5 Hz, CH2), 2.20 (d, 1H, J = 16.5 Hz, CH2), 2.24 (d, 1H, J = 16.5 Hz, CH2), 2.82 (s, 3H, CH3), 5.25 (s, 1H, CH9), 7.18 (d, 2H, J = 8.5 Hz, Ar), 7.57 (d, 2H, J = 8.5 Hz, Ar), 7.68 (d, 2H, J = 8.5 Hz, Ar), 8.19 (d, 2H, J = 8.5 Hz, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 23.6, 27.2, 29.3, 32.5, 34.5, 40.7, 50.1, 113.3, 114.0, 124.1, 124.2, 129.0, 130.5, 133.3, 136.0, 137.6, 147.0, 151.1, 151.6, 163.93, 168.4, 195.6 ppm; IR (KBr): \( \bar{\nu } \) = 3444, 2958, 2874, 1770, 1710, 1672, 1643, 1575, 1519, 1489, 1363, 1244, 1145, 1066, 1031, 979, 827, 738, 698 cm−1; HPLC/MS: m/z = 535 (M+).

2-Benzyl-4-(4-bromophenyl)-9-(4-fluorophenyl)-5,6,7,9-tetrahydro-1H-pyrrolo[3,4-b]quinoline-1,3,8(2H,4H)-trione (5, C30H22BrFN2O3)

Yellow solid; yield: 67% using CH (conventional heating), 64% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.49; m.p.: 206–208 °C; 1H NMR (500 MHz, CDCl3): δ = 1.98–2.07 (m, 2H, CH2), 2.32–2.39 (m, 2H, CH2), 2.57-2.67 (m, 2H, CH2), 4.70 (s, 2H, CH2), 5.49 (s, 1H, CH9), 6.89 (t, 2H, J = 8.5 Hz, Ar), 7.01 (d, 2H, J = 8.5 Hz, Ar), 7.20 (m, 2H, Ar), 7.28-7.35 (m, 5H, Ar), 7.50 (d, 2H, J = 8.5 Hz, Ar) ppm; 13C NMR (125 MHz, CDCl3): δ = 20.4, 27.2, 31.2, 37.0, 41.6, 114.9, 115.1, 116.9, 117.4, 120.4, 127.9, 128.4, 128.8, 129.9, 130.0, 132.9, 136.4, 137.5, 140.3, 142.2, 164.0, 167.8, 172.0, 196.6 ppm; IR (KBr): \( \bar{\nu } \) = 3308, 3119, 2951, 2872, 1761, 1691, 1635, 1541, 1492, 1440, 1357, 1215, 1176, 1134, 1076, 1016, 958, 837, 796, 709 cm−1; HPLC/MS: m/z = 556 (M+).

7-Methyl-9-(4-methylphenyl)-5-(3-nitrophenyl)-5,9-dihydro-1H-pyrrolo[3′,4′:5,6]pyrido[2,3-d]pyrimidine-2,4,6,8(3H,7H)-tetrone (6, C23H17N5O6)

Yellow solid; yield: 74% using CH (conventional heating), 72% using US; TLC (CH2Cl2/MeOH, 5:0.1): R f  = 0.40; m.p.: 205–206 °C; 1H NMR (500 MHz, DMSO-d 6 ): δ = 2.16 (s, 3H, CH3), 2.88 (s, 3H, CH3), 4.36 (s, 1H, CH5), 6.43 (d, 2H, J = 8.0 Hz, Ar), 6.85 (d, 2H, J = 8.0 Hz, Ar), 7.31 (m, 3H, Ar), 7.85 (m, 1H, Ar), 10.89 (s, 1H, NH), 11.14 (s, 1H, NH) ppm; 13C NMR (125 MHz, DMSO-d 6 ): δ = 20.2, 23.5, 52.2, 120.7, 123.5, 123.6, 128.1, 128.3, 134.1, 134.7, 136.4, 136.5, 141.4, 141.5, 146.6, 146.7, 151.1, 166.7, 168.4, 168.8, 172.9 ppm; IR (KBr): \( \bar{\nu } \) = 3358, 3277, 3093, 2924, 2864, 1749, 1712, 1691, 1633, 1527, 1462, 1435, 1394, 1365, 1348, 1259, 1220, 1180, 1114, 1010, 881, 817, 756, 680 cm−1; HPLC/MS: m/z = 459 (M+).