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

Authors: M. Mamaghani; K. Tabatabaeian; R. Araghi; A. Fallah; R. Hossein Nia
Journal: Organic Chemistry International
 (2014)

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## 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).


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## Body

## 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)-one1 (1 mmol), 1,3-indanedione2 (1 mmol), or 1,3-cyclohexadione5 and aldehydes3 (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)νmax⁡=3448, 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)νmax⁡=3448, 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):νmax⁡=3380, 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):νmax⁡=3440, 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, J2C-F=21.0 Hz), 120.3, 120.7, 129.9 (d, J3C-F=8.0 Hz), 130.6, 132.1, 133.9, 136.8, 142.6, 153.3, 156.1, 158.9, 160.6 (d, J1C-F=240.0 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):νmax⁡=3350, 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):νmax⁡=3460, 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):νmax⁡=3450, 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):νmax⁡=3448, 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):νmax⁡=3350, 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):νmax⁡=3211, 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):νmax⁡=3490, 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):νmax⁡=3389, 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):νmax⁡=3203, 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):νmax⁡=3209, 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):νmax⁡=3221, 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 (J2 = 22.0 Hz), 120.4 (J3 = 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 (JC-F1=245.0 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):νmax⁡=3230, 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)νmax⁡=3219, 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):νmax⁡=3119, 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):νmax⁡=3221, 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 (JCF2 = 21.0 Hz), 129.6 (JCF3 = 8.0 Hz), 143.3 (JCF4 = 2.0 Hz), 152.4, 153.5, 153.6, 161.0 (JCF1 = 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):νmax⁡=3221, 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):νmax⁡=3225, 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):νmax⁡=3225, 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):νmax⁡=3223, 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)νmax⁡=3261, 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%.


## 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)-one1 (1 mmol), 1,3-indanedione2 (1 mmol), or 1,3-cyclohexadione5 and aldehydes3 (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)νmax⁡=3448, 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)νmax⁡=3448, 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):νmax⁡=3380, 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):νmax⁡=3440, 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, J2C-F=21.0 Hz), 120.3, 120.7, 129.9 (d, J3C-F=8.0 Hz), 130.6, 132.1, 133.9, 136.8, 142.6, 153.3, 156.1, 158.9, 160.6 (d, J1C-F=240.0 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):νmax⁡=3350, 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):νmax⁡=3460, 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):νmax⁡=3450, 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):νmax⁡=3448, 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):νmax⁡=3350, 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):νmax⁡=3211, 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):νmax⁡=3490, 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):νmax⁡=3389, 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):νmax⁡=3203, 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):νmax⁡=3209, 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):νmax⁡=3221, 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 (J2 = 22.0 Hz), 120.4 (J3 = 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 (JC-F1=245.0 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):νmax⁡=3230, 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)νmax⁡=3219, 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):νmax⁡=3119, 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):νmax⁡=3221, 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 (JCF2 = 21.0 Hz), 129.6 (JCF3 = 8.0 Hz), 143.3 (JCF4 = 2.0 Hz), 152.4, 153.5, 153.6, 161.0 (JCF1 = 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):νmax⁡=3221, 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):νmax⁡=3225, 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):νmax⁡=3225, 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):νmax⁡=3223, 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)νmax⁡=3261, 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%.


## 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)νmax⁡=3448, 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)νmax⁡=3448, 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):νmax⁡=3380, 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):νmax⁡=3440, 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, J2C-F=21.0 Hz), 120.3, 120.7, 129.9 (d, J3C-F=8.0 Hz), 130.6, 132.1, 133.9, 136.8, 142.6, 153.3, 156.1, 158.9, 160.6 (d, J1C-F=240.0 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):νmax⁡=3350, 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):νmax⁡=3460, 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):νmax⁡=3450, 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):νmax⁡=3448, 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):νmax⁡=3350, 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):νmax⁡=3211, 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):νmax⁡=3490, 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):νmax⁡=3389, 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):νmax⁡=3203, 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):νmax⁡=3209, 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):νmax⁡=3221, 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 (J2 = 22.0 Hz), 120.4 (J3 = 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 (JC-F1=245.0 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):νmax⁡=3230, 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)νmax⁡=3219, 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):νmax⁡=3119, 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):νmax⁡=3221, 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 (JCF2 = 21.0 Hz), 129.6 (JCF3 = 8.0 Hz), 143.3 (JCF4 = 2.0 Hz), 152.4, 153.5, 153.6, 161.0 (JCF1 = 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):νmax⁡=3221, 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):νmax⁡=3225, 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):νmax⁡=3225, 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):νmax⁡=3223, 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)νmax⁡=3261, 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).Scheme 1
Synthesis of indenopyrido[2,3-d]pyrimidine (4a–r).Scheme 2
Synthesis of of pyrimido[4,5-b]quinoline6a–f.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)-dione4a as a model reaction. The reaction between equimolar amounts of 6-amino-2-(methylthio)pyrimidin-4(3H)-one1 (prepared by the condensation of thiourea with ethylcyanoacetate in sodium ethoxide and followed by alkylation with alkyliodide [49]), 1,3-indanedione2, 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 of4a 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).Table 1
Effect of various solvents in the synthesis of4aunder conventional conditions and ultrasonic irradiations.
Entry
Solvent
Conventional method
Sonochemical method
Time (min)
Yield (%)a
Time (min)
Yield (%)a
1
Ethylene glycol
180
90
b
25
95
c
2
AcOH
180
86
29
90
3
DMF
210
82
29
88
4
EtOH
220
84
30
88
5
H2O
240
78
41
83
6
Acetone
240
70
42
76
7
CHCl3
270
66
47
70
8
CH3CN
300
60
50
65
aIsolated yield.
bReflux temperature.
c65°C.Figure 1Using the optimized reaction conditions various derivatives of indenopyrido[2,3-d]pyrimidines4a–r (Scheme 1) were prepared in high to excellent yields (85–97%) and lower reaction times (Table 2).Table 2
Synthesis of indenopyrido[2,3-d]pyrimidine 4a–r.
Entry
Product
R
Ar
Time (min)
Yield (%)a
1
4a
Me
4-ClC6H4
25
95
2
4b
Me
C6H5
33
92
3
4c
Me
4-BrC6H4
28 (220)b
95 (91)b
4
4d
Me
4-FC6H4
20 (160)b
97 (85)b
5
4e
Me
2-BrC6H4
30 (220)b
94 (88)b
6
4f
Me
2-ClC6H4
27 (210)b
96 (89)b
7
4g
Me
2-OHC6H4
32 (240)b
90 (90)b
8
4h
Me
2,4-Cl2C6H3
20 (160)b
96 (90)b
9
4i
Me
2-NO2C6H4
22 (170)b
97 (90)b
10
4g
Me
4-OCH3C6H4
35
90
11
4k
Me
4-CH3C6H4
35
93
12
4l
Me
3,4-(OCH3)2C6H3
35 (280)b
90 (85)b
13
4m
Et
2,4-Cl2C6H3
15 (180)b
95 (90)b
14
4n
Et
4-ClC6H4
20 (185)b
89 (80)b
15
4o
Et
2-FC6H4
18
86
16
4p
Et
4-BrC6H4
25
85
17
4q
Et
4-MeSC6H4
22
85
18
4r
Et
C6H5
27
87
aIsolated yield.
bConventional conditions.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)-one1, 1,3-cyclohexadione5, and arylaldehydes3 under the aforementioned optimized reaction conditions and obtained pyrimido[4,5-b]quinoline-4,6-diones6a–f (Scheme 2) in high yields (82–95%) and short reaction times (10–25 min) (Table 3).Table 3
Synthesis of pyrimido[4,5-b]quinoline  6a–f.
Entry
Product
Ar
Time (min)
Yield (%)a
1
6a
4-FC6H4
10 (180)b
95 (90)b
2
6b
1-naphtyl
15 (230)b
93 (87)b
3
6c
4-CH3C6H4
20 (270)b
89 (82)b
4
6d
4-CH3OC6H4
23
87
5
6e
5-methylthiophen-2-yl
25
82
6
6f
4-ClC6H4
17
90
aIsolated yields.
bConventional conditions.The plausible mechanism of this MCRs involves Knoevenagel condensation between CH-acid (2 or5) and aryl aldehydes (3) resulting in the arylidene intermediate7, followed by Michael addition of enaminone1, cyclization, and removal of H2O to form the desired products (4 or6) (Scheme 3).Scheme 3
The plausible mechanism of synthesis of fused pyrimidine derivatives4a–r and6a–f.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.



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*Source: 406869-2014-11-16.xml*