Supporting Information

Supporting Information Synthesis of Pyrido-fused Quinazolinone Derivatives via Copper-catalyzed Domino Reaction Meilin Liu, Miaomiao Shu, Chaochao Yao, Guodong Yin,* Dunjia Wang, and Jinkun Huang* Hubei Collaborative Innovation Center for Rare Metal Chemistry, Hubei Key Laboratory of Pollutant Analysis and Reuse Technology, Hubei Normal University, Huangshi 435002, China. E-mail: gdyin_hbnu@163.com; jxhcm99@qq.com Contents 1. Natural alkaloids bearing 11H-pyrido[2,1-b]quinazolin-11-one fragment.s2 2. General....S2 3. Mechanism study... S3-S4 4. Typical procedure for the synthesis of 3/4........S5 5. Characterization data for compounds 3/4 and 6.....S5-S12 6. 1 H and 13 C NMR spectra of compounds 3/4 and 6...S13-S44

1. Natural alkaloids bearing 11H-pyrido[2,1-b]quinazolin-11-one fragment Scheme S1 2. General All the chemicals were commercially available and used without further purification. All the organic solvents were freshly distilled before use. 1 H and 13 C NMR were recorded in CDCl 3 using Bruker AV 300 MHz spectrometers at 300 and 75 MHz, respectively. Chemical shifts are reported relative to TMS (internal standard). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet), coupling constants (Hz) and integration. Mass spectra were measured on a LCQ Advantage MAX (ESI) and high resolution mass spectra were recorded using a Bruker ultraflextreme MALDI-TOF/TOF (HCCA matrix). IR spectra were obtained as KBr pellet samples using a Nicolet 5700 FTIR spectrometer. Flash column chromatography was performed on silica gel (200 300 mesh). Melting points were determined using an uncorrected X-4 apparatus. The X-ray crystal structure determination was performed using a Bruker SMART APEX CCD system. S2

3. Mechanism study (1) The effect of water on the products Scheme S2 Entry Solvent T (h) Yield 3a/6 b (%) 1 DMF/H 2 O (5:1, v/v, 6 ml) 2 68/12 2 DMF/H 2 O (10:1, v/v, 6 ml) 2 72/5 3 DMF (5 ml) 10 93/trace Reaction conditions: 1a (1.0 mmol), 2a (1.2 mmol), Cu(OAc) 2 H 2 O (0.2 mmol), NaHCO 3 (2.0 mmol) at 120 o C; Isolated yields. Apparently, increasing the amount of water could accelerate the reaction and decrease the yield of 3a. The yield of byproduct 6 increased to 12% when DMF/H 2 O (5:1, v/v, 6 ml) was used as the solvent. Probably, compound 6 was formed by the self-condensation of isatin and its hydrolysis product 2-(2-aminophenyl)-2-oxoacetic acid, as observed by Moskovkina, T. V. (Russ. J. Org. Chem. 2012, 48, 123). Scheme S3 Self-condensation for the formation of tryptanthrin 6 (2) The effect of base on the products It was found that, under the standard conditions, the reaction of isatin (1a) with 2-bromo-6-methylpyridine (2d) gave product 4d in 70% yield. And only trace amount of 2-methylbenzo[b][1,8]naphthyridin-5(10H)-one (4d ) was observed (Scheme 3 in the manuscript and Scheme S4-a). It has been observed that even without additional base, the reaction could also give the corresponding product 3a (entry 21, Table 1 in the manuscript). Herein, we found that in the absence of base NaHCO 3, when 1.1 equiv of Cu(OAc) 2 H 2 O was used, 4d was isolated as the major product in 75% yield and 4d was only obtained in <5% yield (Scheme S4-b). These experimental results were likely to be explained as follows: (1) N-substituted intermediate P1 could undergo the N-cyclization and the C-cyclization two possible pathways after extrusion of carbon monoxide to give corresponding products 4d and 4d respectively. When the methyl group was neighboring to N-atom in pyridine ring, C-cyclization 4d was isolated as the S3

major product (75% yield) due to the less steric hindrance. Meanwhile, little amount of N-cyclization 4d was also observed (<5% yield). It should be noted that when no substituted group was neighboring to N-atom in pyridine ring, the N-cyclization would be the main reaction for strong nucleophilicity of pyridine nitrogen atom. In addition, in the presence of base NaHCO 3, the hydrolysis of P1 would deliver a keto-acid intermediate P4. The sequential intramolecular N-cyclization decarboxylation/aerobic oxidation reaction would give the desired 4d as the major product. Apparently, the ring strain in intermediate P4 was weaker than intermediate P1. Therefore, although the methyl group was neighboring to N-atom in pyridine ring, 4d was obtained as the major product due to the stronger nucleophilicity of pyridine nitrogen atom compared with the aromatic carbon atom and only trace amount of C-cyclization product 4d was observed (Scheme S4-a). In summary, it might be concluded that under the standard reaction conditions (Cu(OAc) 2 H 2 O, NaHCO 3, DMF, 120 o C), the hydrolysis pathway (Path I, Scheme 5 in the manuscript) was preferred. Meanwhile, extrusion of carbon monoxide pathway (Path II, Scheme 5 in the manuscript) was also feasible. Scheme S4 Scheme S5 S4

4. General procedure for the synthesis of 3/4 (3a as an example) A sealed tube was charged with isatin (1a, 147 mg, 1.0 mmol), 2-bromopyridine (2a, 190 mg, 1.2 mmol), Cu(OAc) 2 H 2 O (40 mg, 0.2 mmol) and NaHCO 3 (168 mg, 2.0 mmol), then DMF (5 ml) was added. The resulting mixture was stirred at 120 o C for 10 h. After disappearance of the reactant (monitored by TLC), the mixture was slowly cooled to room temperature and DMF was removed under reduced pressure. Then water (20 ml) was added to the mixture, and extracted with EtOAc three times (3 25 ml). The extract was combined and dried over anhydrous Na 2 SO 4 and evaporation. The residue was purified by column chromatography on silica gel (petroleum ether/etoac) to yield the product 3a as a yellow solid (182 mg, 93% yield). 5. Characterization data for compounds 3/4 and 6 11H-Pyrido[2,1-b]quinazolin-11-one (3a). 1 Yield 93% (182 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.89 (d, J = 7.4 Hz, 1H), 8.48 8.45 (m, 1H), 7.89 7.78 (m, 2H), 7.56 7.46 (m, 3H), 6.90 6.85 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 159.0, 148.5, 147.7, 135.1, 134.1, 127.3, 126.9, 126.7, 126.3, 125.2, 116.3, 112.5; ESI-MS: m/z 196.98 [M+H] +. 2-Methyl-11H-pyrido[2,1-b]quinazolin-11-one (3b). 1 Yield 88% (185 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.87 (d, J = 7.4 Hz, 1H), 8.24 (s, 1H), 7.73 7.66 (m, 2H), 7.49 7.44 (m, 2H), 6.87 6.82 (m, 1H), 2.54 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.9, 147.2, 146.7, 136.9, 135.4, 133.6, 126.71, 126.66, 126.3, 126.2, 116.1, 112.4, 21.4; ESI-MS: m/z 211.05 [M+H] +. 2-Methoxy-11H-pyrido[2,1-b]quinazolin-11-one (3c). 1 Yield 94% (213 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.88 (d, J = 7.4 Hz, 1H), 7.75 (d, J = 8.8 Hz, 2H), 7.51 7.44 (m, 3H), 6.89 6.84 (m, 1H), 3.97 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.7, 157.4, 146.1, 143.7, 132.8, 128.7, 126.9, 126.4 (2C), 116.9, 112.6, 105.1, 55.9; ESI-MS: m/z 226.92 [M+H] +. S5

2-Fluoro-11H-pyrido[2,1-b]quinazolin-11-one (3d). 1 Yield 90% (193 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.85 (d, J = 7.4 Hz, 1H), 8.06 (dd, J 1 = 8.5 Hz, J 2 = 2.5 Hz, 1H), 7.83 7.79 (m, 1H), 7.63 7.51 (m, 3H), 6.92 6.87 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 159.7 ( 1 J C-F = 245.9 Hz), 158.4 ( 4 J C-F = 4.1 Hz), 147.1 ( 4 J C-F = 1.7 Hz), 145.4, 133.9, 129.5 ( 3 J C-F = 8.1 Hz), 126.44, 126.37, 124.5 ( 2 J C-F = 24.8 Hz), 117.0 ( 3 J C-F = 7.4 Hz), 112.9, 111.2 ( 2 J C-F = 23.4 Hz); ESI-MS: m/z 215.01 [M+H] +. 4-Fluoro-11H-pyrido[2,1-b]quinazolin-11-one (3e). 1 Yield 92% (197 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.90 (d, J = 7.4 Hz, 1H), 8.24 (d, J = 8.2 Hz, 1H), 7.68 7.55 (m, 3H), 7.44 7.37 (m, 1H), 6.96 6.91 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.4, 156.6 ( 1 J C-F = 244.5 Hz), 148.0, 138.8 ( 2 J C-F = 12.3 Hz), 134.7, 126.8, 126.7, 124.7 ( 3 J C-F = 7.4 Hz), 122.9 ( 4 J C-F = 4.4 Hz), 119.5 ( 2 J C-F = 18.6 Hz), 118.0, 113.1; ESI-MS: m/z 215.01 [M+H] +. 2-Chloro-11H-pyrido[2,1-b]quinazolin-11-one (3f). 1 Yield 89% (205 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.87 (d, J = 7.4 Hz, 1H), 8.41 (d, J = 1.8 Hz, 1H), 7.79 7.72 (m, 2H), 7.59 7.50 (m, 2H), 6.94 6.89 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.0, 147.7, 147.0, 135.6, 134.4, 130.7, 128.7, 126.7, 126.4, 126.2, 117.0, 112.9; ESI-MS: m/z 231.01 [M+H] +. 2-Bromo-11H-pyrido[2,1-b]quinazolin-11-one (3g). 2 Yield 82% (226 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.86 (d, J = 7.4 Hz, 1H), 8.56 (d, J = 2.3 Hz, 1H), 7.88 (dd, J 1 = 8.9 Hz, J 2 = 2.3 Hz, 1H), 7.65 (d, J = 8.9 Hz, 1H), 7.58 7.48 (m, 2H), 6.92 6.87 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 157.9, 147.9, 147.4, 138.2, 134.5, 129.5, 128.8, 126.8, 126.4, 118.3, 117.4, 113.0; ESI-MS: m/z 275.07 [M+H] +. 3-Bromo-11H-pyrido[2,1-b]quinazolin-11-one (3h). Yield 84% (231 mg); yellow solid; mp 194 195 C; IR (KBr) ν 1633, 1593, 1397, 1349, 1058, 764, 679 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.87 (d, J = 7.3 Hz, 1H), 8.29 (d, J = 8.6 Hz, 1H), 7.96 (d, J = 1.6 Hz, 1H), 7.60 7.49 (m, 3H), 6.94 6.89 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.6, 149.4, 148.5, 134.9, 130.1, 129.5, 128.7, S6

128.6, 126.8, 126.4, 114.9, 112.9; HRMS (MALDI): m/z calcd for C 12 H 7 BrN 2 O: 274.9815, found: 274.9819 [M+H] +. 4-(Trifluoromethyl)-11H-pyrido[2,1-b]quinazolin-11-one (3i). Yield 90% (238 mg); yellow solid; mp 178 179 C; IR (KBr) ν 1632, 1398, 1350, 1123, 761, 478 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.89 (d, J = 7.3 Hz, 1H), 8.66 8.63 (m, 1H), 8.17 (d, J = 7.4 Hz, 1H), 7.65 7.57 (m, 2H), 7.50 (t, J = 7.7 Hz, 1H), 6.98 6.92 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.5, 147.9, 146.2, 134.9, 133.0 ( 3 J C-F = 5.4 Hz), 131.6, 127.2, 126.5, 125.9 ( 2 J C-F = 29.9 Hz), 123.5, 120.1 ( 1 J C-F = 271.7 Hz), 117.2, 113.4; HRMS (MALDI): m/z calcd for C 13 H 7 F 3 N 2 O: 265.0583, found: 265.0580 [M+H] +. 2-Nitro-11H-pyrido[2,1-b]quinazolin-11-one (3j). Yield 75% (181 mg); yellow solid; mp 279 280 C; IR (KBr) ν 1712, 1605, 1337, 1151, 1058, 1084, 762, 685 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 9.35 (d, J = 2.5 Hz, 1H), 8.95 (d, J = 7.3 Hz, 1H), 8.59 (dd, J 1 = 9.2 Hz, J 2 = 2.6 Hz, 1H), 7.86 7.60 (m, 3H), 7.06 (t, J = 7.3 Hz, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.3, 152.2, 149.8, 143.9, 136.7, 128.7, 128.4, 127.1, 126.6, 124.8, 115.3, 114.1; HRMS (MALDI): m/z calcd for C 12 H 7 N 3 O 3 : 242.0560, found: 242.0553 [M+H] +. 6-Methyl-11H-pyrido[2,1-b]quinazolin-11-one (4a). 1 Yield 85% (179 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.80 (dd, J 1 = 7.4 Hz, J 2 = 0.6 Hz, 1H), 8.44 (d, J = 8.0 Hz, 1H), 7.84 7.82 (m, 2H), 7.49 7.44 (m, 1H), 7.38 7.36 (m, 1H), 6.78 (t, J = 7.0 Hz, 1H), 2.60 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 159.5, 148.2, 147.6, 134.7, 134.5, 132.1, 127.4, 127.1, 125.0, 124.8, 116.1, 112.0, 18.6; ESI-MS: m/z 211.09 [M+H] +. 7-Methyl-11H-pyrido[2,1-b]quinazolin-11-one (4b). 3 Yield 92% (193 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.79 (d, J = 7.5 Hz, 1H), 8.43 (dd, J 1 = 8.2 Hz, J 2 = 1.0 Hz, 1H), 7.85 7.74 (m, 2H), 7.47 7.42 (m, 1H), 7.29 (s, 1H), 6.72 (dd, J 1 = 7.4 Hz, J 2 = 1.6 Hz, 1H), 2.42 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.9, 148.8, 147.7, 145.7, 134.9, 127.2, 126.6, 125.8, 124.6, 123.6, S7

115.9, 115.4, 21.3; HRMS (MALDI): m/z calcd for C 13 H 10 N 2 O: 211.0866, found: 211.0868 [M+H] +. 8-Methyl-11H-pyrido[2,1-b]quinazolin-11-one (4c). 3 Yield 84% (177 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.70 (s, 1H), 8.46 (dd, J 1 = 8.3 Hz, J 2 = 1.0 Hz, 1H), 7.87 7.77 (m, 2H), 7.49 7.45 (m, 2H), 7.40 (dd, J 1 = 9.3 Hz, J 2 = 1.9 Hz, 1H), 2.38 (d, J = 1.1 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.7, 148.4, 146.8, 137.4, 134.7, 127.2, 126.7, 125.6, 124.9, 123.4, 122.3, 116.1, 18.2; ESI-MS: m/z 211.08 [M+H] +. 9-Methyl-11H-pyrido[2,1-b]quinazolin-11-one (4d). 4 Yield 70% (147 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.70 (s, 1H), 8.27 (d, J = 8.0 Hz, 1H), 7.79 7.64 (m, 1H), 7.65 (d, J = 8.1 Hz, 1H), 7.39 (t, J = 7.3 Hz, 1H), 7.39 7.29 (m, 2H), 2.98 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 162.4, 149.9, 147.5, 142.5, 134.6, 133.3, 127.0, 126.0, 125.0, 124.8, 118.4, 115.2, 24.6; HRMS (MALDI): m/z calcd for C 13 H 10 N 2 O: 211.0866, found: 211.0872 [M+H] +. 6-Methoxy-11H-pyrido[2,1-b]quinazolin-11-one (4e). Yield 75% (170 mg); yellow solid; mp 190 191 C; IR (KBr) ν 1635, 1529, 1399, 1158, 1058, 750, 684 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.57 (dd, J 1 = 6.2 Hz, J 2 = 2.5 Hz, 1H), 8.45 (dd, J 1 = 8.1 Hz, J 2 = 1.1 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.88 7.82 (m, 1H), 7.53 7.48 (m, 1H), 6.84 6.78 (m, 2H), 4.07 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.9, 151.7, 147.5, 142.6, 134.8, 127.7, 127.1, 125.6, 118.7, 116.5, 111.3, 107.7, 56.7; HRMS (MALDI): m/z calcd for C 13 H 10 N 2 O 2 : 227.0815, found: 227.0811 [M+H] +. 6-Fluoro-11H-pyrido[2,1-b]quinazolin-11-one (4f). Yield 82% (176 mg); yellow solid; mp 208 209 C; IR (KBr) ν 1595, 1398, 1349, 1095, 760, 686, 472 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.70 (d, J = 7.4 Hz, 1H), 8.46 (d, J = 8.0 Hz, 1H), 7.94 7.86 (m, 2H), 7.57 7.52 (m, 1H), 7.28 7.23 (m, 1H), 6.83 6.77 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.4, 154.0 ( 1 J C-F = 255.7 Hz), 147.5, 141.2 ( 2 J C-F = 21.1 Hz), 135.4, 127.6, 127.3, 126.2, 122.8 ( 4 J C-F = 5.6 Hz), S8

116.6, 115.0 ( 2 J C-F = 18.5 Hz), 110.0 ( 3 J C-F = 7.0 Hz); HRMS (MALDI): m/z calcd for C 12 H 7 FN 2 O: 215.0615, found: 215.0619 [M+H] +. 8-Chloro-11H-pyrido[2,1-b]quinazolin-11-one (4g). Yield 91% (210 mg); yellow solid; mp 186 188 C; IR (KBr) ν 1682, 1632, 1398, 1349, 1058, 765, 813, 685 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.91 (s, 1H), 8.45 (d, J = 8.2 Hz, 1H), 7.90 7.78 (m, 2H), 7.55 7.42 (m, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.0, 148.2, 145.9, 135.6, 135.3, 127.5, 127.4, 127.2, 125.9, 124.2, 121.1, 116.2; HRMS (MALDI): m/z calcd for C 12 H 7 ClN 2 O: 231.0320, found: 231.0322 [M+H] +. 8-Bromo-11H-pyrido[2,1-b]quinazolin-11-one (4h). 2 Yield 80% (220 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.97 (d, J = 1.6 Hz, 1H), 8.42 (d, J = 7.8 Hz, 1H), 7.85 (t, J = 7.1 Hz, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.52 7.35 (m, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 157.8, 148.0, 145.8, 137.5, 135.3, 127.4, 127.3, 127.1, 126.5, 125.9, 116.1, 107.6; HRMS (MALDI): m/z calcd for C 12 H 7 BrN 2 O: 274.9815, found: 274.9822 [M+H] +. 8-(Trifluoromethyl)-11H-pyrido[2,1-b]quinazolin-11-one (4i). 1 Yield 79% (209 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 9.18 (d, J = 1.3 Hz, 1H), 8.44 (dd, J 1 = 8.1 Hz, J 2 = 0.9 Hz, 1H), 7.92 7.77 (m, 2H), 7.57 7.52 (m, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.5, 148.1, 146.6, 135.8, 128.9 ( 4 J C-F = 2.1 Hz), 127.7, 127.5, 127.3, 126.5 ( 3 J C-F = 6.2 Hz), 126.3, 122.8 ( 1 J C-F = 269.5 Hz), 116.5, 116.4 ( 2 J C-F = 34.8 Hz); ESI-MS: m/z 265.06 [M+H] +. 11-Oxo-11H-pyrido[2,1-b]quinazoline-8-carbonitrile (4j). 3 Yield 48% (106 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 9.27 (d, J = 0.9 Hz, 1H), 8.47 (dd, J 1 = 8.0 Hz, J 2 = 0.9 Hz, 1H), 7.96 7.81 (m, 2H), 7.62 7.43 (m, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 157.9, 147.9, 145.6, 136.2, 134.6, 131.6, 127.80, 127.75, 127.6, 126.8, 116.6, 115.6, 98.8; ESI-MS: m/z 222.03 [M+H] +. 12H-Quinolino[2,1-b]quinazolin-12-one (4k). 3 S9

Yield 80% (197 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 9.58 (d, J = 9.2 Hz, 1H), 8.46 (dd, J 1 = 8.1 Hz, J 2 = 1.1 Hz, 1H), 7.85 7.74 (m, 2H), 7.64 7.59 (m, 3H), 7.54 7.21 (m, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 163.1, 147.9, 146.4, 135.5, 135.2, 134.6, 129.5, 128.1, 127.5, 126.42, 126.38, 126.1, 125.0, 124.4, 121.8, 120.0; ESI-MS: m/z 247.09 [M+H] +. 5H-Thiazolo[2,3-b]quinazolin-5-one (4l). 3 Yield 93% (188 mg); pink solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.39 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 5.1 Hz, 1H), 7.84 7.78 (m, 1H), 7.68 (d, J = 8.3 Hz, 1H), 7.47 (t, J = 7.1 Hz, 1H), 6.84 (d, J = 5.1 Hz, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.7, 158.0, 148.4, 134.9, 127.1, 126.2, 125.4, 121.2, 116.5, 109.4; ESI-MS: m/z 203.03 [M+H] +. 12H-Benzo[4,5]thiazolo[2,3-b]quinazolin-12-one (4m). 3 Yield 90% (227 mg); white solid; 1 H NMR (300 MHz, CDCl 3 ) 9.03 (dd, J 1 = 8.4 Hz, J 2 = 1.2 Hz, 1H), 8.44 (dd, J 1 = 8.0 Hz, J 2 = 1.2 Hz, 1H), 7.83 7.78 (m, 1H), 7.69 7.62 (m, 2H), 7.53 7.41 (m, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 160.8, 157.0, 147.2, 136.1, 134.9, 127.1, 126.8, 126.7, 125.9, 125.8, 123.7, 121.8, 119.3, 118.6; ESI-MS: m/z 253.07 [M+H] +. 2,8-Dimethyl-11H-pyrido[2,1-b]quinazolin-11-one (4n). Yield 88% (197 mg); yellow solid; mp 218 219 C; IR (KBr) ν 1637, 1397, 1349, 1092, 807, 694, 564 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.67 (s, 1H), 8.23 (s, 1H), 7.71 7.64 (m, 2H), 7.46 7.33 (m, 2H), 2.53 (s, 3H), 2.36 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.7, 146.6, 146.4, 136.9, 136.7, 135.2, 126.6, 126.2, 125.8, 123.5, 122.2, 116.0, 21.4, 18.3; HRMS (MALDI): m/z calcd for C 14 H 12 N 2 O: 225.1022, found: 225.1022 [M+H] +. 2,7-Dimethyl-11H-pyrido[2,1-b]quinazolin-11-one (4o). Yield 89% (200 mg); yellow solid; mp 203 204 C; IR (KBr) ν 1628, 1398, 1349, 1095, 760, 686, 472 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.71 (d, J = 7.5 Hz, 1H), 8.15 (s, 1H), 7.63 7.57 (m, 2H), 7.18 (s, 1H), 6.62 (dd, J 1 = 7.5 Hz, J 2 = 1.7 Hz, 1H), 2.49 (s, 3H), 2.35 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.7, 147.1, 146.8, 145.0, S10

136.7, 134.6, 126.4, 126.0, 125.7, 123.5, 115.6, 115.2, 21.3, 21.2; HRMS (MALDI): m/z calcd for C 14 H 12 N 2 O: 225.1022, found: 225.1018 [M+H] +. 2-Methoxy-8-methyl-11H-pyrido[2,1-b]quinazolin-11-one (4p). 5 Yield 86% (207 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.68 (s, 1H), 7.76 7.72 (m, 2H), 7.49 7.44 (m, 2H), 7.36 7.32 (m, 1H), 3.97 (s, 3H), 2.37 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.5, 157.2, 145.3, 143.7, 136.3, 128.6, 126.7, 125.8, 123.2, 122.5, 116.8, 105.0, 55.8, 18.3; ESI-MS: m/z 241.09 [M+H] +. 8-Chloro-2-methoxy-11H-pyrido[2,1-b]quinazolin-11-one (4q). Yield 91% (237 mg); yellow solid; mp 231 233 C; IR (KBr) ν 1630, 1395, 1103, 1022, 575 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.90 (s, 1H), 7.75 7.73 (m, 2H), 7.52 7.36 (m, 3H), 3.97 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 157.9, 157.7, 144.2, 143.3, 134.3, 128.9, 127.5, 127.0, 123.9, 121.3, 116.9, 105.3, 55.9; HRMS (MALDI): m/z calcd for C 13 H 9 ClN 2 O 2 : 261.0425, found: 261.0424 [M+H] +. 2-Methoxy-8-(trifluoromethyl)-11H-pyrido[2,1-b]quinazolin-11-one (4r). Yield 83% (244 mg); yellow solid; mp 203 204 C; IR (KBr) ν 1701, 1622, 1486, 1380, 1142, 1023, 770, 662 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 9.20 (s, 1H), 7.77 7.74 (m, 2H), 7.56 7.46 (m, 3H), 3.98 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 158.3, 158.2, 144.9, 143.2, 129.1, 127.8, 127.6, 127.3, 126.3 ( 3 J C-F = 6.0 Hz), 123.0 ( 1 J C-F = 269.5 Hz), 117.3, 116.6 ( 2 J C-F = 34.8 Hz), 105.6, 55.9; HRMS (MALDI): m/z calcd for C 14 H 9 F 3 N 2 O 2 : 295.0689, found: 295.0692 [M+H] +. 2,8-Dichloro-11H-pyrido[2,1-b]quinazolin-11-one (4s). Yield 81% (215 mg); yellow solid; mp 234 235 C; IR (KBr) ν 1629, 1398, 1347, 1095, 806, 760, 684, 485 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.88 (s, 1H), 8.39 (d, J = 2.1 Hz, 1H), 7.80 7.71 (m, 2H), 7.47 (s, 2H); 13 C NMR (75 MHz, CDCl 3 ) δ 157.1, 146.6, 145.9, 135.89, 135.86, 131.5, 128.9, 127.5, 126.3, 124.2, 121.7, 116.9; HRMS (MALDI): m/z calcd for C 12 H 6 Cl 2 N 2 O: 264.9930, found: 264.9927 [M+H] +. 2,8-Dibromo-11H-pyrido[2,1-b]quinazolin-11-one (4t). S11

Yield 76% (269 mg); yellow solid; mp 262 264 C; IR (KBr) ν 1629, 1397, 1350, 474 cm 1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 8.99 (d, J = 1.6 Hz, 1H), 8.56 (d, J = 2.2 Hz, 1H), 7.91 (dd, J 1 = 8.8 Hz, J 2 = 2.3 Hz, 1H), 7.67 7.38 (m, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 156.8, 146.9, 146.0, 138.5, 137.9, 129.6, 129.0, 127.5, 126.6, 119.2, 117.4, 108.2; HRMS (MALDI): m/z calcd for C 12 H 6 Br 2 N 2 O: 354.8900, found: 354.8899 [M+H] +. Indolo[2,1-b]quinazoline-6,12-dione (6). 6 Yield 12% (15 mg); yellow solid; 1 H NMR (300 MHz, CDCl 3 ) δ 8.64 (d, J = 8.1 Hz, 1H), 8.45 (d, J = 7.8 Hz, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.94 7.77 (m, 3H), 7.68 (t, J = 7.8 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 182.5, 158.1, 146.6, 146.3, 144.3, 138.3, 135.1, 130.7, 130.2, 127.5, 127.2, 125.4, 123.7, 121.9, 118.0. 2-Methylbenzo[b][1,8]naphthyridin-5(10H)-one (4d ). 7 Yield 75% (157 mg); yellow solid; 1 H NMR (300MHz, CDCl 3 ) δ 9.45 (s, 1H), 8.67 (d, J = 8.1Hz, 1H), 8.46 (d, J = 8.0Hz, 1H), 7.70 7.65 (m, 1H), 7.38 7.28 (m, 2H), 7.13 (d, J = 8.1 Hz, 1H), 2.65 (s, 3H); 13 C NMR (75MHz, CDCl 3 ) δ 178.5, 164.3, 150.4, 140.0, 136.9, 134.0, 127.2, 122.3, 121.8, 118.5, 116.8, 114.2, 25.0; HRMS (MALDI): m/z calcd for C 13 H 10 N 2 O: 211.0866, found: 211.0859 [M+H] +. References [1] Liang, D. D.; He, Y. M.; Zhu, Q. Org. Lett. 2014, 16, 2748. [2] Chen, J. B.; Feng, J. B.; Natte, K.; Wu, X. F. Chem.- Eur. J. 2015, 21, 16370. [3] Sun, J.; Tan, Q. T.; Yang, W. S.; Liu, B. X.; Xu, B. Adv. Synth. Catal. 2014, 356, 388. [4] Pellón, R. F.; Docampo, M. L.; Kunakbaeva, Z.; Gómez, V.; Vélez-Castro, H. Synth. Commun. 2006, 36, 481. [5] Maity, A.; Mondal, S.; Paira, R.; Hazra, A.; Naskar, S.; Sahu, K. B.; Saha, P.; Banerjee, S.; Mondal, N. B. Tetrahedron Lett. 2011, 52, 3033. [6] Wang, C.; Zhang, L. P.; Ren, A. N.; Lu, P.; Wang, Y. G. Org. Lett. 2013, 15, 2982. [7] Suarez-Ortiz, G. A.; Sharma, P.; Amezquita-Valencia, M.; Arellano, I.; Cabrera, A.; Rosas, N. Tetrahedron Lett. 2011, 52, 1641. S12

6. 1 H and 13 C NMR spectra of compounds 3/4 and 6 Figure S-1 1 H NMR spectrum of compound 3a Figure S-2 13 C NMR spectrum of compound 3a S13

Figure S-3 1 H NMR spectrum of compound 3b Figure S-4 13 C NMR spectrum of compound 3b S14

Figure S-5 1 H NMR spectrum of compound 3c Figure S-6 13 C NMR spectrum of compound 3c S15

Figure S-7 1 H NMR spectrum of compound 3d Figure S-8 13 C NMR spectrum of compound 3d S16

Figure S-9 1 H NMR spectrum of compound 3e Figure S-10 13 C NMR spectrum of compound 3e S17

Figure S-11 1 H NMR spectrum of compound 3f Figure S-12 13 C NMR spectrum of compound 3f S18

Figure S-13 1 H NMR spectrum of compound 3g Figure S-14 13 C NMR spectrum of compound 3g S19

Figure S-15 1 H NMR spectrum of compound 3h Figure S-16 13 C NMR spectrum of compound 3h S20

Figure S-17 1 H NMR spectrum of compound 3i Figure S-18 13 C NMR spectrum of compound 3i S21

Figure S-19 1 H NMR spectrum of compound 3j Figure S-20 13 C NMR spectrum of compound 3j S22

Figure S-21 1 H NMR spectrum of compound 4a Figure S-22 13 C NMR spectrum of compound 4a S23

Figure S-23 1 H NMR spectrum of compound 4b Figure S-24 13 C NMR spectrum of compound 4b S24

Figure S-25 1 H NMR spectrum of compound 4c Figure S-26 13 C NMR spectrum of compound 4c S25

Figure S-27 1 H NMR spectrum of compound 4d Figure S-28 13 C NMR spectrum of compound 4d S26

Figure S-29 1 H NMR spectrum of compound 4e Figure S-30 13 C NMR spectrum of compound 4e S27

Figure S-31 1 H NMR spectrum of compound 4f Figure S-32 13 C NMR spectrum of compound 4f S28

Figure S-33 1 H NMR spectrum of compound 4g Figure S-34 13 C NMR spectrum of compound 4g S29

Figure S-35 1 H NMR spectrum of compound 4h Figure S-36 13 C NMR spectrum of compound 4h S30

Figure S-37 1 H NMR spectrum of compound 4i Figure S-38 13 C NMR spectrum of compound 4i S31

Figure S-39 1 H NMR spectrum of compound 4j Figure S-40 13 C NMR spectrum of compound 4j S32

Figure S-41 1 H NMR spectrum of compound 4k Figure S-42 13 C NMR spectrum of compound 4k S33

Figure S-43 1 H NMR spectrum of compound 4l Figure S-44 13 C NMR spectrum of compound 4l S34

Figure S-45 1 H NMR spectrum of compound 4m Figure S-46 13 C NMR spectrum of compound 4m S35

Figure S-47 1 H NMR spectrum of compound 4n Figure S-48 13 C NMR spectrum of compound 4n S36

Figure S-49 1 H NMR spectrum of compound 4o Figure S-50 13 C NMR spectrum of compound 4o S37

Figure S-51 1 H NMR spectrum of compound 4p Figure S-52 13 C NMR spectrum of compound 4p S38

Figure S-53 1 H NMR spectrum of compound 4q Figure S-54 13 C NMR spectrum of compound 4q S39

Figure S-55 1 H NMR spectrum of compound 4r Figure S-56 13 C NMR spectrum of compound 4r S40

Figure S-57 1 H NMR spectrum of compound 4s Figure S-58 13 C NMR spectrum of compound 4s S41

Figure S-59 1 H NMR spectrum of compound 4t Figure S-60 13 C NMR spectrum of compound 4t S42

Figure S-61 1 H NMR spectrum of compound 6 Figure S-62 13 C NMR spectrum of compound 6 S43

Figure S-63 1 H NMR spectrum of compound 4d Figure S-64 13 C NMR spectrum of compound 4d S44