Experimental Section

Supporting Information Available：Full experimental details and copies of the 1H and 13C NMR spectra for all new compounds.

Experimental Section

General Procedure for the Synthesis of the Title Compounds 8a-8s.

All the microwave assisted polymer-supported reactions described throughout the manuscript have been performed under CEM Discover Microwave system at the frequency of 2450 Hz (0-300 W) in open vessel system.

Poly(ethyleneglycol) 1 (PEG5000, 1.0 g, 0.20 mmol) in dichloromethane (5 mL) was added to a solution of Fmoc-protected amino acid 2 (0.24 mmol, 1.2 equiv) in dichloromethane (5 mL) in the presence N,N’–dicyclohexylcarbodiimide (DCC, 0.072g, 0.35 mmol, 1.2 equiv) as coupling reagent and a catalytic amount of N,N’-dimethylamino pyridine (DMAP, 0.003 g) under microwave irradiation (40 oC) for 15 minutes to afford the ester 3. The precipitated dicyclohexyl urea (DCU) was filtered through a fritted funnel and the reaction mixtures were precipitated by slow addition of excess of cold ether (100 mL). The precipitated ester conjugate was then filtered through a fritted funnel and washed several times to remove the byproducts and dried. To a solution of 3 in dichloromethane (9.0 mL), piperidine (1.0 mL) was added slowly and allowed to stir at room temperature for one hour to afford the aminoester. The solution was concentrated using rotary evaporation and precipitated by slow addition of cold ether (100 mL) and filtered through a fritted funnel to afford the compound 4 in quantitative yield. The polymer bound amine conjugate 4 was treated with dinitrodiflurobenzene (0.60 mmol, 3.0 equiv) and triethylamine (1.20 mmol, 6.0 equiv) in dichloromethane (5 mL) under microwave irradiation (40 oC) for 7 minutes. The reaction mixtures were purified by precipitation and the polymer conjugate 5 was obtained. To a solution of polymer bound dinitrofluroamine 5 in of dichloromethane (5 mL), various primary amines (0.56 mmol, 3.0 equiv) in dichloromethane (5 mL) was added and the mixtures were irradiated in microwave cavity (40 oC) for 10 min to afford the PEG-immobilized dinitrodiamines 6. The simultaneous reduction of the two nitro groups was proceeded by using palladium (0.04 mmol, 0.2 equiv) and ammonium formate (10 equiv, 2.00 mmol) in methanol under microwave irradiation (65 oC) for 10 minutes until the TLC showed complete release of the desired compound from the polymer support. Finally the insoluble palladium/charcoal was removed first by filtration to afford the crude compound 7. To a solution of crude 7 in dichloromethane (10 mL), isothiocyanates (3.0 equiv, 0.60 mmol), mercury chloride (3.0 equiv, 0.60 mmol) and triethylamine (6.0 equiv, 1.20 mmol) were added and then exposed to microwave irradiation (40 oC) for 10 minutes. After completion, the mixtures were filtered to remove the byproducts and subjected to rotavapor to evaporate the solvent. The obtained slurry was loaded on silica gel column and eluted with a mixture of ethyl acetate and hexane (2:1) to furnish the target compound 8 in high purity and good yields (See Table 1).

1-Isobutyl-7-isopropyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8a). 1H NMR (300 MHz, CD3OD) δ 7.62 (s, 1H), 7.58-7.55 (m, 2H), 7.38-7.33 (m, 2H), 7.20 (s, 1H), 7.12-7.06 (m, 1H), 4.06 (d, J = 7.6 Hz, 2H), 3.57-3.48 (m, 1H), 2.36-2.23 (m, 1H), 1.30 (d, J = 6.8 Hz, 6H), 0.99 (d, J = 6.7 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 161.2, 155.0, 154.3, 143.3, 139.4, 132.3, 128.4, 128.2, 127.5, 123.3, 120.7, 106.6, 99.5, 47.9, 29.3, 28.2, 19.3, 18.8; IR (cm-1, neat): 2964, 1649; MS (EI) m/z: 375 (M+); HRMS calcd for C22H25N5O: m/z 375.2059; Found 375.2057.

1,7-Diisopropyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8b). 1H NMR (300 MHz, CD3OD) δ 7.86 (s, 1H), 7.54-7.50 (m, 2H), 7.38-7.33 (m, 2H), 7.20 (s, 1H), 7.11-7.06 (m, 1H), 3.66-3.43 (m, 2H), 1.71 (d, J = 6.8 Hz, 6H), 1.32 (d, J = 6.8 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 161.4, 155.2, 153.7, 129.9, 129.5, 128.7, 127.9, 127.3, 127.1, 123.1, 120.5, 108.6, 99.9, 47.0, 30.0, 19.3, 19.2; IR (cm-1, neat): 2960, 1649; MS (EI) m/z: 361 (M+); HRMS calcd for C21H23N5O: m/z 361.1903; Found 361.1895.

2-(m-Toluidino)-1,7-diisopropyl-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8c). 1H NMR (300 MHz, CD3OD) δ 7.85 (s, 1H), 7.36 (s, 1H), 7.31-7.22 (m, 2H), 7.20 (s, 1H), 6.90 (d, J = 7.2 Hz, 1H), 3.60-3.51 (m, 1H), 3.31-3.29 (m, 1H), 2.35 (s, 3H), 1.70 (d, J = 6.8 Hz, 6H), 1.31 (d, J = 6.8 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 162.6, 156.5, 155.0, 140.0, 131.2, 129.8, 129.2, 128.6, 128.4, 125.1, 122.4, 118.9, 109.9, 101.2, 100.8, 48.3, 31.3, 21.6, 20.8, 20.7; IR (cm-1, neat): 2963, 1658; MS (EI) m/z: 375 (M+). HRMS calcd for C22H25N5O: m/z 375.2059; Found 375.2061.

1-Cyclohexyl-7-isopropyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8d). 1H NMR (300 MHz, CD3OD) δ 7.88 (s, 1H), 7.53-7.51 (m, 2H), 7.37-7.35 (m, 2H), 7.19 (s, 1H), 7.10-7.05 (m, 1H), 4.50-4.42 (m, 1H), 3.66-3.61 (m, 1H), 2.43-2.31 (m, 2H), 2.03-1.94 (m, 4H), 1.60-1.51 (m, 4H), 1.31 (d, J = 6.8 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 161.3, 155.1, 153.7, 144.1, 140.0, 130.2, 128.9, 127.8, 127.2, 122.9, 120.9, 108.9, 99.7, 54.8, 30.2, 29.9, 25.6, 24.9, 19.3; IR (cm-1, neat): 2926, 1645; MS (EI) m/z: 401 (M+); HRMS calcd for C24H27N5O: m/z 401.2216; Found 401.2215.

1-Cyclopentyl-7-isopropyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8e). 1H NMR (500 MHz, DMSO) δ 12.1 (s, 1H), 9.1 (s, 1H), 7.80 (d, J = 7.5 Hz, 2H), 7.49 (s, 1H), 7.35-7.32 (m, 2H), 7.18 (s, 1H), 7.01-6.99 (m, 1H), 5.12-5.05 (m, 1H), 3.46-3.41 (m, 1H), 2.20-2.15 (m, 2H), 2.07-2.02 (m, 2H), 1.76-1.74 (m, 1H), 1.21 (d, J = 7.0 Hz, 6H); 13C NMR (125 MHz, DMSO) δ 154.1, 150.6, 140.1, 128.7, 127.6, 126.6, 122.1, 121.8, 118.9, 117.8, 107.8, 100.2, 100.1, 54.5, 29.7, 28.5, 24.5, 20.2 ; IR (cm-1, neat): 2926, 1652; MS (EI) m/z: 387 (M+); HRMS calcd for C23H25N5O: m/z 387.2059; Found 387.2059.

1-Butyl-7-isopropyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8f). 1H NMR (300 MHz, CD3OD) δ 7.64 (s, 1H), 7.60-7.57 (m, 2H), 7.39-7.34 (m, 2H), 7.20 (s, 1H), 7.20 (m, 1H), 4.25 (t, J = 7.2 Hz, 2H), 3.54 (m, 1H), 1.88-1.78 (m, 2H), 1.48-1.38 (m, 2H), 1.32 (s, 3H), 1.30 (s, 3H), 0.98 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CD3OD) δ 161.1, 155.0, 140.5, 132.4, 132.0, 128.4, 128.6, 128.2, 127.5, 123.1, 120.4, 106.1, 99.6, 42.0, 30.6, 30.0, 19.6, 19.3, 12.8; IR (cm-1, neat): 2956, 1686; MS (EI) m/z: 375 (M+); HRMS calcd for C22H25N5O: m/z 375.2059; Found 375.2074.

2-(2-Chlorophenylamino)-1-isobutyl-7-isopropyl-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8g). 1H NMR (300 MHz, CD3OD) δ 11.96 (s, 1H), 8.59 (d, J = 6.7 Hz, 1H), 7.59 (s, 1H), 7.50 (s, 1H), 7.42-7.36 (m, 2H), 7.02 (m, 1H), 3.91 (d, J = 6.9 Hz, 2H), 3.68 (m, 1H), 2.38 (m, 1H), 1.38 (d, J = 6.5 Hz, 6H), 1.09 (d, J = 6.2 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 162.5, 155.7, 151.5, 135.4, 131.9, 129.1, 128.9, 128.2, 127.6, 123.5, 119.9, 107.0, 101.7, 50.9, 30.5, 30.1, 28.7, 20.4; IR (cm-1, neat): 2954, 1658; MS (EI) m/z: 409 (M+); HRMS calcd for C22H24ClN5O: m/z 409.1669; Found 409.1666.

2-(m-Toluidino)-1-cyclohexyl-7-isopropyl-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8h). 1H NMR (500 MHz, d-THF) δ 11.00 (s, 1H), 7.73 (s, 1H), 7.63-7.53 (m, 2H), 7.13 (t, J = 8.0 Hz, 1H), 7.08 (s, 1H), 6.76 (d, J = 7.0 Hz, 1H), 4.39 (m, 1H), 2.57 (m, 1H), 2.48-2.36 (m, 2H), 2.31 (m, 3H), 1.97-1.91 (m, 4H), 1.53-1.49 (m, 4H), 1.26 (d, J = 7.0 Hz, 6H); 13C NMR (125 MHz, d-THF) δ 162.4, 155.2, 152.6, 138.2, 130.5, 129.1, 128.9, 128.3, 123.3, 123.2, 120.2, 116.9, 110.1, 100.9, 100.8, 55.5, 31.3, 30.9, 26.9, 26.0, 21.7, 20.7; IR (cm-1, neat): 2915, 1644; MS (EI) m/z: 415 (M+); HRMS calcd for C25H29N5O: m/z 415.2372; Found 415.2364.

7-Benzyl-2-(2-chlorophenylamino)-1-cyclohexyl-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8i). 1H NMR (300 MHz, CD3OD) δ 7.64-7.61 (m, 2H), 7.51 (s, 1H), 7.35-7.31 (m, 2H), 7.29-7.28 (m, 1H), 7.25-7.12 (m, 4H), 6.59 (s, 1H), 4.22-4.20 (dd, J = 5.7 Hz, 1.1 Hz, 2H), 4.08 (m, 1H), 2.37-2.32 (m, 2H), 2.15-2.10 (m, 2H), 1.86-1.81 (m, 2H), 1.70-1.64 (m, 4H); 13C NMR (75 MHz, CD3OD) δ 167.9, 154.8, 148.2, 137.5, 132.2, 131.0, 129.6, 129.5, 128.9, 128.7, 128.4, 128.0, 127.1, 126.4, 126.0, 124.9, 98.1, 97.8, 67.7, 38.7, 30.2, 28.7, 23.5; IR (cm-1, neat): 2928, 1651; MS (EI) m/z: 483 (M+); HRMS calcd for C28H26ClN5O: m/z 483.1826; Found 483.1797.

2-(2-Chlorophenylamino)-1,7-diisobutyl-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8j). 1H NMR (300 MHz, CD3OD) δ 7.53 (m, 1H), 7.47 (s, 1H), 7.44 (m, 1H), 7.31-7.28 (m, 1H), 7.18-7.06 (m, 2H), 3.99-3.98 (m, 2H), 2.66 (d, J = 7.0 Hz, 2H), 2.58 (m, 1H), 2.20 (m, 1H), 0.96 (d, J = 6.5 Hz, 6H), 0.91 (d, J = 7.0 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 184.4, 158.4, 157.7, 157.0, 147.5, 138.7, 135.3, 131.0, 130.3, 130.1, 129.3, 129.2, 127.9, 107.5, 100.0, 43.0, 29.4, 28.9, 28.8, 23.0, 20.4; IR (cm-1, neat): 2949, 1660; MS (EI) m/z: 423 (M+); HRMS calcd for C23H26ClN5O: m/z 423.1826; Found 423.1830.

2-(m-Toluidino)-1,7-diisobutyl-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8k). 1H NMR (300 MHz, CD3OD) δ 7.54 (s, 1H), 7.41 (s, 1H), 7.34 (d, J = 7.9 Hz, 1H), 7.23 (m, 1H), 6.91 (d, J = 7.4 Hz, 1H), 4.04 (d, J = 7.6 Hz, 2H), 3.30 (m, 1H), 2.72 (d, J = 7.2 Hz, 2H), 2.35 (s, 3H), 2.31-2.22 (m, 2H), 0.98 (d, J = 6.6 Hz, 6H), 0.97 (d, J = 6.7 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 155.2, 154.1, 152.9, 142.0, 137.6, 137.0, 130.8, 126.9, 126.3, 126.2, 122.5, 119.8, 116.3, 104.4, 98.0, 47.4, 40.1, 26.7, 26.4, 20.1, 18.6, 17.2; IR (cm-1, neat): 2957, 1655; MS (EI) m/z: 403 (M+); HRMS calcd for C24H29N5O: m/z 403.2372; Found 403.2371.

2-(m-Toluidino)-7-isobutyl-1-isopropyl-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8l). 1H NMR (300 MHz, CD3OD) δ 7.80 (s, 1H), 7.36 (s, 1H), 7.31-7.22 (m, 2H), 7.21 (s, 1H), 6.91 (d, J = 7.3 Hz, 1H), 3.57 (m, 1H), 2.74 (d, J = 7.4 Hz, 2H), 2.35 (s, 3H), 2.25 (m, 1H), 1.70 (d, J = 6.8 Hz, 6H), 1.00 (d, J = 6.7 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 158.4, 157.1, 155.1, 145.7, 141.2, 140.0, 131.3, 129.8, 129.1, 129.0, 125.2, 122.5, 119.0, 109.5, 101.2, 43.1, 28.3, 23.1, 23.0, 21.5, 20.9; IR (cm-1, neat): 2956, 1647; MS (EI) m/z: 389 (M+); HRMS calcd for C23H27N5O: m/z 389.2216; Found 389.2195.

7-Isobutyl-1-isopropyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8m). 1H NMR (300 MHz, CD3OD) δ 7.46 (s, 1H), 7.38-7.33 (m, 2H), 7.28-7.21 (m, 3H), 6.61 (s, 1H), 5.84 (m, 1H), 2.64 (d, J = 7.2 Hz, 2H), 1.27 (m, 1H), 1.06 (d, J = 6.8 Hz, 3H), 1.00 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.6 Hz, 1.1 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 157.6, 156.7, 149.1, 141.4, 130.5, 130.0, 129.1, 128.4, 126.9, 121.9, 120.3, 99.5, 99.3, 54.2, 42.8, 28.4, 23.0, 22.3; IR (cm-1, neat): 2954, 1645; MS (EI) m/z: 375 (M+); HRMS calcd for C22H25N5O: m/z 375.2059; Found 375.2053.

1,7-Diisobutyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8n). 1H NMR (300 MHz, CD3OD) δ 7.58-7.56 (m, 2H), 7.54 (s, 1H), 7.38-7.33 (m, 2H), 7.19 (s, 1H), 7.09 (d, J = 7.4 Hz, 1H), 4.05 (d, J = 7.6 Hz, 2H), 3.31-3.29 (m, 1H), 2.71 (d, J = 7.2 Hz, 2H), 2.29 (m, 1H), 0.98 (d, J = 6.6 Hz, 12H); 13C NMR (75 MHz, CD3OD) δ 156.8, 155.6, 154.4, 145.9, 139.4, 132.4, 128.6, 127.9, 127.8, 123.2, 120.6, 106.0, 99.7, 49.0, 41.6, 28.0, 26.9, 21.4, 18.7; IR (cm-1, neat): 2927, 1642; MS (EI) m/z: 389 (M+); HRMS calcd for C23H27N5O: m/z 389.2216; Found 389.2216.

7-Benzyl-1-isobutyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8o). 1H NMR (300 MHz, CD3OD) δ 7.61-7.53 (m, 3H), 7.40-7.35 (m, 4H), 7.29-7.13 (m, 5H), 4.17 (s, 2H), 3.62 (s, 2H), 3.47 (m, 1H), 0.99 (d, J = 6.5 Hz, 6H); 13C NMR (75 MHz, CD3OD) δ 158.8, 158.6, 149.8, 141.5, 139.2, 133.8, 132.3, 130.4, 130.3, 129.4, 129.2, 127.4, 127.0, 123.3, 120.6, 110.3, 99.8, 40.32, 34.7, 24.9, 20.1; IR (cm-1, neat): 2925, 1646; MS (EI) m/z: 423 (M+); HRMS calcd for C26H25N5O: m/z 423.2059; Found 423.2039.

7-Benzyl-1-cyclopentyl-2-(phenylamino)-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8p). 1H NMR (300 MHz, CD3OD) δ 11.33 (s, 1H), 7.71 (m, 1H), 7.68 (s, 1H), 7.54 (s, 1H), 7.53-7.50 (m, 2H), 7.30-7.28 (m, 4H), 7.23-7.15 (m, 3H), 6.60 (s, 1H), 4.23-4.20 (m, 2H), 2.37-2.34 (m, 2H), 2.09-1.95 (m, 2H), 1.72-1.64 (m, 4H); 13C NMR (75 MHz, CD3OD) δ 169.3, 157.2, 156.8, 149.6, 139.0, 135.9, 133.8, 133.5, 130.3, 130.1, 129.4, 129.3, 129.2, 128.6, 127.4, 100.3, 99.8, 69.0, 40.1, 31.6, 30.1, 24.9, 24.0; IR (cm-1, neat): 2958, 1652; MS (EI) m/z: 435 (M+); HRMS calcd for C27H25N5O: m/z 435.2059; Found 435.2061.

2-(Allylamino)-7-benzyl-1-butyl-1H-imidazo[4,5-g]quinoxalin-6(5H)-one (8q). 1H NMR (300 MHz, CD3OD) δ 11.90 (s, 1H), 7.39-7.35 (m, 3H), 7.27 (s, 1H), 7.23-7.20 (m, 2H), 6.56 (s, 1H), 5.89 (m, 1H), 5.12-5.06 (m, 2H), 4.55 (m, 1H), 4.41-4.18 (m, 4H), 4.01 (m, 1H), 3.66 (m, 1H), 1.76-1.58 (m, 4H), 0.92 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CD3OD) δ 182.1, 156.2, 155.5, 144.9, 137.2, 134.0, 133.2, 129.5, 129.3, 128.4, 126.6, 126.2, 123.4, 116.3, 99.1, 53.4, 48.0, 39.5, 29.7, 20.0, 13.8; IR (cm-1, neat): 2956, 1660; MS (EI) m/z: 387 (M+); HRMS calcd for C23H25N5O: m/z 387.2059; Found 387.2057.