3.2. Synthesis of Substituted tert-Butyl 3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylates 8a–e
A mixture of substituted phenylhydrazine hydrochloride (6.9 mmol) and 4,4-piperidinediol hydrochloride (8.5 mmol) in aqueous HCl solution (20 mL, 2.0 mol/L) was stirred at 60 °C for 16 h. After cooling to room temperature, the mixture was basified to pH > 12 with 25% NaOH solution. The precipitate formed was filtered off, washed with water and petroleum ether, and dried under reduced pressure to give the corresponding substituted 1,2,3,4-tetrahydro-γ-carbolines, which were used in the next step without further purification. To a solution of substituted 1,2,3,4-tetrahydro-γ-carboline in THF (20 mL), di-tert-butyl dicarbonate (8.2 mmol) was added at 0 °C, and the mixture was stirred at rt for 2 h. The solvent was removed under reduced pressure to give the crude product. Purification was performed by column chromatography on silica gel using ethyl acetate/petroleum ether (boiling range 60–90 °C) (1:2, v/v) as eluent to afford compounds 8a–e.
tert-Butyl 3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (
8a) [
16]. White solid (1.65 g, 88% yield in two steps); mp 145–146 °C; IR: ν 3,306, 3,065, 2,977, 2,916, 2,838, 1,655, 1,465, 1,428, 1,361, 1,161, 749, 663 cm
−1;
1H-NMR (CDCl
3): δ 7.97 (s, 1H), 7.46 (d,
J = 7.5 Hz, 1H), 7.31 (d,
J = 8.0 Hz, 1H), 7.15 (t,
J = 7.5 Hz, 1H), 7.10 (t,
J = 7.5 Hz, 1H), 4.64 (s, 2H), 3.82 (m, 2H), 2.82 (t,
J = 5.5 Hz, 2H), 1.51 (s, 9H); HRMS calculated for C
16H
21N
2O
2 [M+H]
+: 273.1598, found: 273.1596.
tert-Butyl 8-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (
8b) [
17]. White solid (1.68 g, 85% yield in two steps); mp 167–168 °C; IR: ν 3,307, 3,012, 2,974, 2,918, 2,839, 1,665, 1,475, 1,431, 1,360, 1,170, 761, 674 cm
−1;
1H-NMR (CDCl
3): δ 7.81 (s, 1H), 7.23 (s, 1H), 7.19 (d,
J = 8.0 Hz, 1H), 6.97 (d,
J = 8.0 Hz, 1H), 4.61 (s, 2H), 3.81 (br s,2H), 2.80 (br s, 2H), 2.44 (s, 3H), 1.50 (s, 9H); HRMS calculated for C
17H
23N
2O
2 [M+H]
+: 287.1754, found: 287.1753.
tert-Butyl 8-methoxy-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (
8c) [
18]. White solid (1.81g, 84% yield in two steps); mp 170–171 °C; IR: ν 3,267, 2,972, 2,930, 2,840, 1,657, 1,472, 1,428, 1,368, 1,143, 865 cm
−1;
1H-NMR (CDCl
3): δ 7.77 (s, 1H), 7.20 (d,
J = 8.5 Hz, 1H), 6.89 (d,
J = 2.5 Hz, 1H), 6.80 (dd,
J1 = 8.5 Hz,
J2 = 2.5 Hz, 1H), 4.61 (s, 2H), 3.86 (s, 3H), 3.81 (t,
J = 5.5 Hz, 1H), 2.81 (t,
J = 5.5 Hz, 1H), 1.51 (s, 9H); HRMS calculated for C
17H
23N
2O
3 [M+H]
+: 303.1703, found: 303.1702.
tert-Butyl 8-bromo-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (
8d) [
19]. Slightly yellow solid (1.99 g, 82% yield in two steps); mp 177–178 °C (lit 177–179 °C); IR: ν 3,287, 3,007, 2,973, 2,926, 2,871, 2,837, 1,668, 1,589, 1,476, 1,461, 1,427, 1,361, 1,291, 1,232, 1,164, 675 cm
−1;
1H-NMR (CDCl
3): δ 8.11 (s, 1H), 7.55 (s, 1H), 7.21 (d, 1H,
J = 8.5 Hz), 7.16 (d,
J = 8.5 Hz, 1H), 4.58 (s, 2H), 3.79 (t,
J = 5.0 Hz, 1H), 2.81 (t,
J = 5.0 Hz, 1H), 1.51 (s, 9H); HRMS calculated for C
16H
20BrN
2O
2 [M+H]
+: 351.0703, found: 351.0701.
tert-Butyl 6-chloro-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (8e). White solid (1.84 g, 87% yield in two steps); mp 185–186 °C; IR: ν 3,262, 2,973, 2,924, 2,850, 1,671, 1,625, 1,469, 1,428, 1,361, 1,253, 1,159, 771, 691 cm−1; 1H-NMR (CDCl3): δ 8.17 (s, 1H), 7.34 (d, J = 7.0 Hz, 1H), 7.14 (d, J = 7.5 Hz, 1H), 7.02 (dd, J1 = 8.0 Hz, J2 = 7.5 Hz, 1H), 4.62 (s, 2H), 3.82 (br s, 2H), 2.85 (br s, 2H), 1.51 (s, 9H); 13C NMR (125 MHz, CDCl3): δ 155.1, 133.0, 126.9, 120.8, 120.2, 116.1, 108.4, 80.0, 41.2, 40.4, 28.4, 23.4; HRMS calculated for C16H20ClN2O2 [M+H]+: 307.1208, found: 307.1205.
3.3. Synthesis of Other 2-Substituted-1,2,3,4-tetrahydro-γ-carbolines 8f–i
Acetyl chloride (2.4 mmol) was added dropwise at 0 °C to a solution of 1,2,3,4-tetrahydro-γ-carboline (2.0 mmol) in anhydrous CH2Cl2 (20 mL) containing triethylamine (1.0 mL). The reaction mixture stirred at room temperature until the 1,2,3,4-tetrahydro-γ-carboline disappeared (as monitored by TLC). The solvent and excess reagents were removed under reduced pressure to give the crude product. Purification was performed by column chromatography on silica gel using ethyl acetate/petroleum ether (boiling range 60–90 °C) (2:1, v/v) as eluent to afford 8f. The acetyl chloride was replaced by benzoyl chloride, benzyl chloroformate or p-toluenesulfonyl chloride for the synthesis of 8g, 8h and 8i, respectively.
1-(3,4-Dihydro-1H-pyrido[4,3-b]indol-2(5H)-yl)ethanone (
8f) [
20]. Off-white solid (360 mg, 84% yield); mp 256–257 °C (lit. 256–257 °C); IR: ν 3,143, 3,060, 2,945, 2,866, 1,604, 1,447, 1,359, 1,228, 1,146, 746 cm
−1;
1H-NMR (DMSO-d
6) analysis revealed the presence of two rotamers present in a 1.5:1 ratio: δ 10.89 (s, 1H, major rotamer), 10.87 (s, 1H, minor rotamer), 7.40 (m, 1H), 7.28 (dd,
J1 = 8.0 Hz,
J2 = 3.0 Hz, 1H), 7.01–7.05 (m, 1H), 6.95 (dd,
J1 = 14.0,
J2 = 7.0 Hz, 1H), 4.64 (s, 2H, minor rotamer), 4.62 (s, 2H, major rotamer), 3.83 (t,
J = 6.0 Hz, 2H, minor rotamer), 3.76 (t,
J = 6.0 Hz, 2H, major rotamer), 2.86 (t,
J = 5.5 Hz, 2H, major rotamer), 2.74 (t,
J = 5.5 Hz, 2H, minor rotamer), 2.13 (s, 3H, major rotamer), 2.12 (s, 3H, minor rotamer); ESI-MS:
m/z 215.07 [M+H]
+.
(3,4-Dihydro-1H-pyrido[4,3-b]indol-2(5H)-yl)(phenyl)methanone (8g). Off-white solid (492 mg, 89% yield); mp 204–206 °C; IR: ν 3,198, 3,059, 2,903, 2,840, 1,612, 1,577, 1,444, 1,237, 743, 709 cm−1; 1H NMR (CDCl3) analysis revealed the presence of two rotamers present in a 1.1:1 ratio: δ 8.05 (br s, 1H, major rotamer), 8.02 (br s, 1H, minor rotamer), 7.45–7.53 (m, 5H), 7.25–7.31 (m, 2H), 7.03–7.18 (m, 2H), 4.97 (s, 2H, minor rotamer), 4.66 (s, 2H, major rotamer), 4.16 (br s, 2H, major rotamer), 3.75 (br s, 2H, minor rotamer), 2.98 (br s, 2H, major rotamer), 2.86 (br s, 2H, minor rotamer); 13C-NMR (125 MHz, CDCl3): δ 171.4 (major rotamer), 171.1 (minor rotamer), 136.0 (major rotamer), 135.8 (minor rotamer), 132.4, 130.8, 129.9 (major rotamer), 129.7 (minor rotamer), 128.6 (major rotamer), 128.5 (minor rotamer), 127.1 (major rotamer), 126.7 (minor rotamer), 125.5 (minor rotamer), 124.9 (major rotamer), 121.7 (minor rotamer), 121.6 (major rotamer), 119.6 (minor rotamer), 110.8 (major rotamer), 106.9 (minor rotamer), 106.6 (major rotamer), 45.5 (major rotamer), 45.1 (minor rotamer), 40.3 (major rotamer), 40.2 (minor rotamer), 24.2 (minor rotamer), 23.1 (major rotamer); HRMS (ESI) calculated for C18H17N2O [M+H]+: 277.1335, found: 277.1339.
Benzyl 3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (
8h) [
21]. White solid (551 mg, 90% yield); mp 115–117 °C; IR: ν 3,387, 3,019, 2,931, 2,858, 1,701, 1,465, 1,434, 1,240, 1,151, 752 cm
−1;
1H-NMR (CDCl
3): δ 7.91 (br s, 1H), 7.31–7.43 (m, 7H), 7.15 (t,
J = 7.5 Hz, 1H), 7.08 (t,
J = 7.5 Hz, 1H), 5.20 (s, 2H), 4.73 (s, 2H), 3.87–3.90 (m, 2H), 2.82–2.85 (m, 2H); HRMS (ESI) calculated for C
19H
19N
2O
2 [M+H]
+: 307.1441, found: 307.1440.
2-Tosyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (
8i) [
13]. Light yellow solid (574 mg, 88% yield); mp 187–188 °C (lit. 187–189 °C)
1H-NMR (CDCl
3): 7.86 (br s, 1H), 7.50 (d,
J = 8.0 Hz, 2H), 7.37 (d,
J = 7.5 Hz, 1H), 7.31 (d,
J = 8.0 Hz, 2H), 7.26 (d,
J = 5.5 Hz, 1H), 7.14 (t,
J = 7.5 Hz, 1H), 7.08 (t,
J = 7.5 Hz, 1H), 4.38 (s, 2H), 3.51 (t,
J = 6.0 Hz, 1H), 2.87 (t,
J = 6.0 Hz, 1H), 2.41 (s, 3H).
3.4. Synthesis of Substituted Dihydropyrrolo[3.2-b]quinolones 10a–i
Substituted-1,2,3,4-tetrahydro-γ-carbolines (8a–i, 0.5 mmol), sodium hydroxide powder (1.0 mmol) and anhydrous DMF (5.0 mL) were placed in a 25 mL round-bottomed flask equipped with a calcium chloride drying tube. The mixture was stirred for 5–8 h at room temperature until the substrate disappeared. The reaction mixture was concentrated in vacuo and the residue was partitioned between water (10 mL) and ethyl acetate (20 mL). The organic layer was separated and the aqueous layer was further extracted with ethyl acetate (2 × 20 mL). The combined organic layer was washed with brine (20 mL), dried over Na2SO4 and evaporated in vacuo. The crude product was purified by column chromatography on silica gel using ethyl acetate/petroleum ether (boiling range 60–90 °C) (1:1, v/v) as eluent to give 10a-i.
tert-Butyl 9-oxo-2,3,4,9-tetrahydro-1H-pyrrolo[3,2-b]-quinoline-1-carboxylate (10a). Off-white solid (135 mg, 94% yield); mp 159–161 °C; IR: ν 3,071, 2,984, 2,931, 2,626, 1,687, 1,621, 1,442, 1,380, 1,153, 1,031, 862, 753 cm−1; 1H-NMR (CDCl3): δ 12.47 (s, 1H), 8.23 (d, J = 7.5 Hz, 1H), 7.84 (d, J = 8.5 Hz, 1H), 7.56 (dt, J1 = 8.5 Hz, J2 = 1.8 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H), 4.02 (t, J = 8.5 Hz, 1H), 3.31 (t, J = 8.5 Hz, 1H), 1.59 (s, 9H); 13C-NMR (CDCl3): δ 157.5, 155.1, 147.1, 145.9, 128.4, 127.6, 124.9, 122.5, 121.5, 117.2, 83.7, 46.4, 30.5, 29.3; ESI-MS: m/z 287.02 [M+H]+; Anal. Calcd for C16H18N2O3: C, 67.12; H, 6.34; N, 9.78; found: C, 67.43; H, 6.48; N, 9.53.
tert-Butyl 7-methyl-9-oxo-2,3,4,9-tetrahydro-1H-pyrrolo[3,2-b]quinoline-1-carboxylate (10b). Off-white solid (138 mg, 92% yield); mp 185–186 °C; IR: ν 2,977, 2,934, 2,646, 1,665, 1,620, 1,569, 1,453, 1,387, 1,150, 1,034, 857 cm−1; 1H-NMR (CDCl3): δ 12.40 (s, 1H), 7.99 (s, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.38 (dd, J1 = 8.5 Hz, J2 = 2.0 Hz, 1H), 3.99 (t, J = 8.5 Hz, 1H), 3.27 (t, J = 8.5 Hz, 1H), 2.51 (s, 3H), 1.59 (s, 9H); 13C-NMR (CDCl3): δ 156.5, 155.1, 145.6, 145.5, 134.7, 130.6, 127.3, 121.4, 121.3, 171.2, 83.6, 46.4, 30.4, 28.3, 21.6; ESI-MS: m/z 300.94 [M+H]+; Anal. Calcd for C17H20N2O3: C, 67.98; H, 6.71; N, 9.33; found: C, 67.95; H, 6.82; N, 9.41.
tert-Butyl 7-methoxy-9-oxo-2,3,4,9-tetrahydro-1H-pyrrolo[3,2-b]quinoline-1-carboxylate (10c). Off-white solid (141 mg, 89% yield); mp 151–152 °C; IR: ν 3,103, 2,977, 2,931, 2,605, 1,685, 1,659, 1,617, 1,446, 1,392, 1,148, 1,030, 856 cm−1; 1H-NMR (CDCl3): δ 12.46 (s, 1H), 7.75 (d, J = 9.0 Hz, 1H), 7.50 (s, 1H), 7.21 (d, J = 9.0 Hz, 1H), 4.01 (t, J = 8.0 Hz, 1H), 3.93 (s, 3H), 3.28 (t, J = 8.0 Hz, 1H), 1.59 (s, 9H); 13C-NMR (CDCl3): δ 157.0, 155.2, 154.9, 145.0, 142.8, 129.0, 122.2, 120.6, 117.5, 100.6, 83.7, 55.5, 46.6, 30.2, 28.3; ESI-MS: m/z 316.88 [M+H]+; Anal. Calcd for C17H20N2O4: C, 64.54; H, 6.37; N, 8.86; found: C, 64.30; H, 6.48; N, 8.64.
tert-Butyl 7-bromo-9-oxo-2,3,4,9-tetrahydro-1H-pyrrolo[3,2-b]quinoline-1-carboxylate (10d). Light yellow solid (168 mg, 92% yield); mp 179–180 °C; IR: ν 2,979, 2,928, 2,655, 1,664, 1,615, 1,440, 1,379, 1,153, 1,032, 851 cm−1; 1H-NMR (CDCl3): δ 12.49 (s, 1H), 8.37 (d, J = 2.0 Hz, 1H), 7.69 (d, J = 9.0 Hz, 1H), 7.61 (dd, J1 = 9.0 Hz, J2 = 2.0 Hz, 1H), 4.04 (t, J = 8.5 Hz, 2H), 3.30 (t, J = 8.5 Hz, 2H), 1.59 (s, 9H); 13C-NMR (CDCl3): δ 158.0, 155.1, 145.6, 144.9, 131.7, 129.3, 124.9, 122.9, 118.8, 117.8, 84.0, 46.4, 30.4, 28.3; ESI-MS: m/z 364.86 [M+H]+. Anal. Calcd for C16H17BrN2O3: C, 52.62; H, 4.69; N, 7.67; found: C, 52.90; H, 4.72; N, 7.50.
tert-Butyl 5-chloro-9-oxo-2,3,4,9-tetrahydro-1H-pyrrolo[3,2-b]quinoline-1-carboxylate (10e). White solid (149 mg, 93% yield); mp 163–164 °C; IR: ν 2,974, 2,924, 2,672, 1,654, 1,621, 1,441, 1,371, 1,311, 1,157, 1,036, 827, 754 cm−1; 1H-NMR (CDCl3): δ 12.61 (s, 1H), 8.15 (d, J = 8.5 Hz, 1H), 7.66 (d, J = 7.5 Hz, 1H), 7.31 (t, J1 = 8.0 Hz, J2 = 8.0 Hz, 1H), 4.04 (t, J = 8.5 Hz, 2H), 3.40 (t, J = 8.5 Hz, 2H), 1.59 (s, 9H); 13C-NMR (CDCl3): δ 158.5, 155.2, 146.1, 143.3, 131.6, 128.6, 124.7, 123.1, 121.7, 117.9, 84.0, 46.5, 30.8,28.3; ESI-MS: m/z 320.87 [M+H]+; Anal. Calcd for C16H17ClN2O3: C, 59.91; H, 5.34; N, 8.73; found: C, 60.31; H, 5.50; N, 8.82.
1-Acetyl-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (10f). Light yellow solid (99 mg, 87% yield); mp 196–197 °C; IR: ν 3,057, 2,935, 2,363, 1,606, 1,455, 923, 774 cm−1; 1H-NMR (CDCl3): δ 13.14 (s, 1H), 8.26 (d, J = 8.5 Hz, 1H), 7.85 (d, J = 8.5 Hz, 1H), 7.61 (t, J = 7.0 Hz, 1H), 7.45 (t, J = 7.5 Hz, 1H), 4.10 (t, J = 8.5 Hz, 2H), 3.39 (t, J = 8.5 Hz, 2H), 2.33 (s, 3H); 13C-NMR (CDCl3): δ 170.3, 157.2, 148.2, 147.8, 129.3, 127.6, 125.1, 123.3, 121.4, 117.8, 48.0, 30.7, 23.0; ESI-MS: m/z 229.13 [M+H]+; Anal. Calcd for C13H12N2O2: C, 68.41; H, 5.30; N, 12.27; found: C, 68.67; H, 5.46; N, 11.94.
1-Benzoyl-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (10g). Light yellow solid (129 mg, 89% yield); mp 213–214 °C; IR: ν 3,075, 2,995, 2,951, 1,639, 1,582, 1,508, 1,462, 1,389, 1,323, 766 cm−1; 1H-NMR (CDCl3): δ 12.12 (s, 1H), 8.33 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.64–7.66 (m, 3H), 7.48–7.58 (m, 4H), 4.14 (t, J = 8.0 Hz, 2H), 3.32 (t, J = 8.0 Hz, 2H); 13C-NMR (CDCl3): δ 170.3, 157.6, 149.0, 147.8, 134.6, 131.3, 129.6, 128.8, 127.5, 127.2, 125.4, 123.3, 121.7, 118.4, 60.0, 31.3; ESI-MS: m/z 291.14 [M+H]+; Anal. Calcd for C18H14N2O2: C, 74.47; H, 4.86; N, 9.65; found: C, 74.21; H, 4.90; N, 9.58.
Benzyl-9-oxo-2,3,4,9-tetrahydro-1H-pyrrolo[3,2-b]quinoline-1-carboxylate (10h). Light yellow solid (138 mg, 86% yield); mp 153–154 °C; IR: ν 3,115, 2,963, 2,909, 1,669, 1,570, 1,501, 1,473, 1,161, 846, 775, 741 cm−1; 1H-NMR (CDCl3): δ 12.21 (s, 1H), 8.23 (d, J = 8.5 Hz, 1H), 7.84 (d, J = 8.5 Hz, 1H), 7.56–7.59 (m, 1H), 7.35–7.45 (m, 6H), 5.31 (s, 2H), 4.08 (t, J = 8.5 Hz, 2H), 3.31 (t, J = 8.5 Hz, 2H); 13C-NMR (CDCl3): δ 157.2, 155.4, 147.2, 146.0, 135.1, 128.7, 128.6, 128.4, 127.6, 125.1, 122.5, 121.4, 116.6, 69.1, 46.2, 30.4; ESI-MS: m/z 321.12 [M+H]+; Anal. Calcd for C19H16N2O3: C, 71.24; H, 5.03; N, 8.74; found: C, 71.10; H, 5.05; N, 8.59.
1-Tosyl-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (
10i) [
13]. Light yellow solid (65 mg, 38% yield); mp 207–208 °C (lit. 207–209 °C);
1H-NMR (DMSO-d
6): 12.06 (s, 1H), 8.15 (d,
J = 7.0 Hz, 1H), 7.65 (d,
J = 8.0 Hz, 2H), 7.60 (m, 1H,), 7.46 (d,
J = 9.0 Hz, 1H), 7.32–7.35 (m, 3H), 3.99 (t,
J = 7.5 Hz, 2H), 2.48–2.50 (m, 2H), 2.36 (s, 3H).
3.5. Synthesis of Dihydropyrrolo[3,2-b]quinolone Hydrochlorides 11a–e
2-Boc-dihydropyrrolo[3,2-b]quinolones (10a–e, 0.5 mmol) was dissolved in a mixture of HCl saturated ethyl acetate (5 mL) and methanol (5 mL) under nitrogen. The reaction mixture was refluxed for 6–8 h and cooled to room temperature, the precipitate was filtered and washed with cool ethyl acetate to afford 11a–e.
2,3-Dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one hydrochloride (11a). Yellow solid (107 mg, 96% yield); mp > 250 °C; IR (KBr): ν 3,091, 2,983, 2,670, 1,635, 1,595, 1,536, 1,465, 1,418, 1,355, 1,266, 756, 682 cm−1. 1H NMR (500 MHz, D2O): δ 8.17 (d, 1H, J = 8.0 Hz), 7.80 (t, 1H, J = 8.0 Hz), 7.54–7.61 (m, 2H), 4.06 (t, J = 7.5 Hz, 2H), 3.58 (t, J = 7.5 Hz, 2H); 13C NMR (125 MHz, D2O): δ 170.2, 150.6, 139.6, 133.2, 125.1, 124.5, 124.0, 118.8, 114.8, 43.8, 28.5; HRMS (ESI) calculated for C11H11N2O [M+H]+: 187.0866, found: 187.0857.
7-Methyl-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one hydrochloride (11b). Yellow solid (111 mg, 94% yield); mp > 250 °C; IR (KBr): ν 3,088, 2,988, 2,447, 1,633, 1,570, 1,528, 1,483, 1,418, 1,360, 829 cm−1; 1H NMR (500 MHz, D2O): δ 7.76 (s, 1H), 7.49 (dd, J1 = 8.5 Hz, J2 = 1.5 Hz, 1H), 7.33 (d, J = 8.5 Hz, 1H), 3.94 (t, J = 8.0 Hz, 2H), 3.44 (t, J = 8.0 Hz, 2H), 2.38 (s, 3H); 13C NMR (125 MHz, D2O): δ 169.6, 149.7, 137.4, 135.5, 134.5, 124.2, 122.6, 118.3, 114.6, 43.7, 28.3, 20.2; HRMS (ESI) calculated for C12H12N2NaO [M+Na]+: 223.0842, found: 223.0838.
7-Methoxy-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one hydrochloride (11c). Yellow solid (119 mg, 94% yield); mp > 250 °C; IR (KBr): ν 2,813, 2,649, 2,460, 1,613, 1,509, 1,475, 1,348, 1,246, 853 cm−1; 1H NMR (500 MHz, D2O): δ 7.15 (d, J = 9.0 Hz, 1H), 7.11 (s, 1H), 7.03 (d, J = 9.0 Hz, 1H), 3.92 (t, J = 8.0 Hz, 2H), 3.72 (s, 3H), 3.40 (t, J = 8.0 Hz, 2H); 13C NMR (125 MHz, D2O): δ 168.9, 156.3, 149.1, 134.4, 125.6, 123.0, 120.2, 114.4, 103.4, 55.6, 43.9, 28.3; HRMS (ESI) calculated for C12H13N2O2 [M+H]+: 217.0971, found: 217.0964.
7-Bromo-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one hydrochloride (11d). Brown solid (143 mg, 95% yield); mp > 250 °C; IR (KBr): ν 2,853, 2,757, 2,469, 1,629, 1,574, 1,518, 1,461, 852 cm−1; 1H NMR (500 MHz, D2O): δ 7.88 (s, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.20 (d, J = 9.0 Hz,1H), 3.98 (t, J = 8.0 Hz, 2H), 3.53 (t, J = 8.0 Hz, 2H); 13C NMR (125 MHz, D2O): δ 168.8, 151.0, 138.3, 135.5, 126.3, 125.8, 120.6, 117.9, 115.4, 43.7, 28.7; HRMS (ESI) calculated for C11H10BrN2O [M+H]+: 264.9971, found: 264.9969.
5-Chloro-2,3-dihydro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one hydrochloride (11e). Slightly yellow solid (121 mg, 94% yield); mp > 250 °C; IR (KBr): ν 3,084, 2,915, 2,483, 1,630, 1,594, 1,422, 750 cm−1; 1H NMR (500 MHz, D2O): δ 7.80 (d, J = 8.5 Hz, 1H), 7.62 (d, J = 7.5 Hz, 1H), 7.22 (t, 1H, J = 8.0 Hz), 3.95 (t, J = 8.0 Hz, 2H), 3.47 (t, J = 8.0 Hz, 2H); 13C NMR (125 MHz, D2O): δ 170.5, 151.8, 136.9, 133.7, 126.8, 125.8, 124.0, 123.4, 116.6, 49.5, 44.4, 29.7; HRMS (ESI) calculated for C11H10ClN2O [M+H]+: 221.0476, found: 221.0472.
3.6. Synthesis of Pyrrolo[3.2-b]quinolones (12a–e)
Dihydropyrrolo[3,2-b]quinolone hydrochloride (11a–e, 0.5 mmol) was mixed with potassium carbonate (1.0 mmol) in ethanol (10 mL) and refluxed for 4–6 h. The mixture was concentrated in vacuo, the residue was purified by column chromatography on silica gel using ethyl acetate/petroleum ether (boiling range 60–90 °C) (4:1, v/v) as eluent to give 12a–e.
1H-Pyrrolo[3,2-b]quinolin-9(4H)-one (
12a) [
12]. Light yellow solid (90 mg, 98% yield); mp > 250 °C; IR: ν 3,164, 3,030, 2,900, 1,690, 1,637, 1,595, 1,518, 1,459, 1,413, 750, 669 cm
−1;
1H-NMR (DMSO-d
6): δ 8.25 (d,
J = 7.0 Hz, 1H), 7.56 (dt,
J1 = 8.5 Hz,
J2 = 1.5 Hz, 1H), 7.49 (d,
J = 8.0 Hz, 1H), 7.37 (t,
J = 3.0 Hz, 1H), 7.15 (t,
J = 7.5 Hz, 1H), 6.20 (t,
J = 2.5 Hz, 1H); HRMS (ESI) calculated for C
22H
17N
4O
2 [2M+H]
+: 369.1346, found: 369.1345.
7-Methyl-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (
12b) [
12]. Yellow solid (96 mg, 97% yield); mp > 250 °C; IR: ν 3,170, 3,029, 2,930, 1,584, 1,520, 1,475, 1,404, 1,356, 1,302, 1,144, 787 cm
−1;
1H-NMR (DMSO-d
6): δ 11.77 (s, 1H), 11.66 (s, 1H), 8.05 (s, 1H), 7.36–7.42 (m, 3H), 6.18 (s, 1H), 2.41 (s, 3H); HRMS (ESI) calculated for C
12H
11N
2O [M+H]
+: 199.0866, found: 199.0864.
7-Methoxy-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (
12c) [
12]. Yellow solid (103 mg, 96% yield); mp 250 °C; IR: ν 3,173, 3,015, 2,930, 1,583, 1,522, 1,478, 1,403, 1,356, 1,270, 756 cm
−1;
1H-NMR (CD
3OD): δ 7.76 (d,
J = 2.5 Hz, 1H), 7.45–7.47 (m, 2H), 7.23 (dd,
J1 = 9.0 Hz,
J2 = 2.5 Hz, 1H), 6.26 (d,
J = 3.0 Hz, 1H), 3.86(s, 3H);
13C-NMR (CD
3OD): δ 167.3, 155.9, 138.7, 136.0, 131.1, 123.7, 123.2, 121.7, 120.1, 105.0, 95.6, 56.1; HRMS (ESI) calculated for C
12H
11ClN
2O
2 [M+H]
+: 215.0815, found: 215.0814.
7-Bromo-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (
12d) [
12]. Yellow solid (126 mg, 96% yield); mp > 250 °C; IR: ν 3,150, 2,924, 1,636, 1,594, 1,514, 1,454, 1,262, 1,153, 1,031, 810, 755 cm
−1;
1H-NMR (CD
3OD): δ 8.47 (d,
J = 2.0 Hz, 1H), 7.65 (dd, 1H,
J1 = 9.0 Hz,
J2 = 2.0 Hz), 7.48 (d, 1H,
J = 3.0 Hz), 7.44 (d, 1H,
J = 8.5 Hz), 6.29 (d, 1H,
J = 3.0 Hz);
13C-NMR (CD
3OD): δ 166.9, 139.5, 138.8, 134.8, 131.3, 128.7, 124.1, 121.7, 120.4, 95.9; HRMS (ESI) calculated for C
11H
7BrN
2O [M+H]
+: 262.9815, found: 262.9814.
5-Chloro-1H-pyrrolo[3,2-b]quinolin-9(4H)-one (12e). Yellow solid (107 mg, 98% yield); mp > 250 °C; IR: ν 3,149, 3,023, 2,916, 1,627, 1,583, 1,514, 1,442, 1,355, 1,103, 774 cm−1; 1H-NMR (CD3OD): δ 8.29 (d, J = 8.5 Hz, 1H), 7.63 (d, J = 7.5 Hz, 1H), 7.44 (d, J = 3.0 Hz, 1H), 7.13 (dd, J1 = 8.0 Hz, J2 = 7.5 Hz, 1H), 6.40 (d, J = 3.0 Hz, 1H); 13C-NMR (CD3OD): δ 168.2, 139.1, 137.7, 132.4, 131.6, 126.2, 124.9, 122.9, 122.1, 121.9, 97.3; HRMS (ESI) calculated for C11H7ClN2NaO [M+Na]+; 241.0139, found: 241.0135.