3.2. Synthesis
The synthetic route for the compounds B1~C12 were outlined in
Figure 3.
The general procedure for the synthesis of compounds B1~7 [
27] is presented here.
To a solution of anthranilic acid (A1~7, 5 mmol) in N,N-dimethylformamide (DMF, 10 mL), anhydrous potassium carbonate (K2CO3, 0.51 g, 3.7 mmol) was added and heated at 100 °C for 1 h. The solution was cooled to 50 °C and chloroacetone (0.46 g, 5 mmol) was added. The solution was stirred at 50 °C for 1 h, cooled to room temperature, and poured into ice/water (50 mL); then, stirring was continued for 1 h at 0 to 10 °C. Precipitate was observed, then filtered and washed with water (15 mL), and dried under a vacuum to give the products B1~7 as solids in 70~84% yields.
2-oxopropyl 2-amino-5-bromobenzoate (B1): Yellow solid, yield 83.9%, m.p., 85–87 °C. 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 2.4 Hz, 1H), 7.36 (dd, J = 8.8, 2.4 Hz, 1H), 6.58 (d, J = 8.8 Hz, 1H), 5.74 (s, 2H), 4.84 (s, 2H), 2.23 (s, 4H).
2-oxopropyl 2-amino-5-iodobenzoate (B2): Brown solid, yield 84.3%, m.p., 81–83 °C. 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 2.2 Hz, 1H), 7.50 (dd, J = 8.7, 2.2 Hz, 1H), 6.47 (d, J = 8.7 Hz, 1H), 4.83 (s, 2H), 2.23 (s, 3H).
2-oxopropyl 2-amino-5-methylbenzoate (B3): Black solid, yield 81.7%, m.p., 81–83 °C. 1H NMR (400 MHz, CDCl3) δ 7.74 (dd, J = 2.0, 1.0 Hz, 1H), 7.13 (dd, J = 8.3, 2.2 Hz, 1H), 6.62 (d, J = 8.4 Hz, 1H), 4.82 (s, 2H), 2.24 (s, 3H), 2.23 (s, 3H).
2-oxopropyl 2-amino-4-methoxybenzoate (B4): Yellow solid, yield 80.6%, m.p., 87–89 °C. 1H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 9.0 Hz, 1H), 6.70 (s, 2H), 6.29 (d, J = 2.5 Hz, 1H), 6.17 (dd, J = 9.0, 2.5 Hz, 1H), 4.88 (s, 2H), 3.74 (s, 3H), 2.13 (s, 3H).
2-oxopropyl 2-amino-4-(trifluoromethyl) benzoate (B5): Green solid, yield 73.6%, m.p., 84–86 °C. 1H NMR (400 MHz, CDCl3) δ 8.07–7.97 (m, 1H), 6.92 (d, J = 1.7 Hz, 1H), 6.87 (dd, J = 8.5, 1.7 Hz, 1H), 4.87 (s, 2H), 2.24 (s, 3H).
2-oxopropyl 2-amino-4,5-difluorobenzoate (B6): Yellow solid, yield 78.8%, m.p., 88–90 °C. 1H NMR (400 MHz, CDCl3) δ 7.74 (dd, J = 11.2, 8.9 Hz, 1H), 6.44 (dd, J = 12.0, 6.6 Hz, 1H), 4.83 (s, 2H), 2.23 (s, 3H).
2-oxopropyl 2-amino-4,5-dimethoxybenzoate (B7): Yellow solid, yield 70.6%, m.p., 82–84 °C. 1H NMR (400 MHz, CDCl3) δ 7.36 (s, 1H), 6.15 (s, 1H), 4.81 (s, 2H), 3.88 (s, 3H), 3.84 (s, 3H), 2.23 (s, 2H).
The general procedure for the synthesis of compounds C1~7 [
27] is presented here.
The intermediate B1~7 (5 mmol) was heated in reflux N-methyl-2-pyrrolidone (NMP, 4 mL) for 8 h and then cooled to 50 °C. Ethyl acetate (10 mL) was added; upon cooling to room temperature, a crude solid precipitate was observed. The precipitate was stirred at 0 to 5 °C for 30 min, then filtered and washed with water (3 mL), cold ethyl acetate (3 mL), and cold dichloromethane (4 mL) to give products C1~7 as solids in 54~71% yields.
6-bromo-3-hydroxy-2-methylquinolin-4(1H)-one (C1): Brown solid, yield 71.7%, m.p., 181–183 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.72 (s, 1H), 8.34 (s, 1H), 8.18 (d, J = 2.4 Hz, 1H), 7.66 (dd, J = 8.9, 2.4 Hz, 1H), 7.48 (d, J = 8.9 Hz, 1H), 2.37 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 167.9, 139.1, 136.4, 133.1, 133.0, 127.0, 124.3, 120.8, 114.5, 14.6. HRMS for C10H9BrNO2+ [M + H]+ 253.9811, found 253.9815.
3-hydroxy-6-iodo-2-methylquinolin-4(1H)-one (C2): Blank solid, yield 70.4%, m.p., 188–190 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 8.39 (d, J = 1.9 Hz, 1H), 7.79 (dd, J = 8.7, 2.1 Hz, 1H), 7.34 (d, J = 8.7 Hz, 1H), 2.37 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 167.6, 139.0, 138.3, 136.7, 133.4, 133.1, 124.8, 120.7, 86.2, 14.6. HRMS for C10H9INO2+ [M + H]+ 301.9672, found 301.9651.
3-hydroxy-2,6-dimethylquinolin-4(1H)-one (C3): Pink solid, yield 68.6%, m.p., 168–170 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 7.94–7.80 (m, 1H), 7.48–7.29 (m, 2H), 2.39 (s, 3H), 2.35 (s, 3H). HRMS for C11H12NO2+ [M + H]+ 190.0863, found 190.0835.
3-hydroxy-7-methoxy-2-methylquinolin-4(1H)-one (C4): White solid, yield 54.1%, m.p., 206–208 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 7.99 (d, J = 8.9 Hz, 1H), 6.93–6.68 (m, 2H), 3.83 (s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 169.1, 161.2, 139.5, 138.0, 131.1, 126.8, 117.3, 113.0, 98.3, 55.7, 14.4. HRMS for C11H12NO3+ [M + H]+ 206.0812, found 206.0789.
3-hydroxy-2-methyl-7-(trifluoromethyl)quinolin-4(1H)-one (C5): White solid, yield 57.9%, m.p., 187–189 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.89 (s, 1H), 8.31 (d, J = 8.5 Hz, 1H), 7.87 (s, 1H), 7.57–7.28 (m, 1H), 2.41 (d, J = 1.6 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ 168.5, 139.9, 136.8, 133.73, 130.2 (d, J = 31.6 Hz), 127.1, 124.8, 124.5 (q, J = 270 Hz), 117.37 (q, J = 3.2 Hz), 115.83 (q, J = 4.6 Hz) 14.74. HRMS for C11H9F3NO2+ [M + H]+ 244.0580, found 244.0558.
6,7-difluoro-3-hydroxy-2-methylquinolin-4(1H)-one (C6): White solid, yield 58.7%, m.p., 178–180 °C.1H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 7.93 (dd, J = 11.2, 8.8 Hz, 1H), 7.44 (dd, J = 11.4, 6.8 Hz, 1H), 2.36 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 168.1 (d, J = 2.8 Hz), 151.7 (dd, J = 249.3, 16.0 Hz), 146.45 (dd, J = 243.5, 14.7 Hz), 138.5, 134.4 (d, J = 10.7 Hz), 133.2, 119.7 (d, J = 5.0 Hz), 111.66 (dd, J = 16.3, 2.0 Hz), 105.8 (d, J = 20.6 Hz), 14.6. HRMS for C10H8F2NO2+ [M + H]+ 212.0518, found 212.0489.
3-hydroxy-6,7-dimethoxy-2-methylquinolin-4(1H)-one (C7): White solid, yield 67.2%, m.p., 191–193 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.32 (s, 1H), 7.39 (s, 1H), 6.89 (s, 1H), 3.84 (s, J = 5.6 Hz, 6H), 2.32 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 168.0, 152.5, 146.3, 137.7, 133.6, 130.1, 116.7, 103.8, 98.8, 56.0, 55.9, 14.4. HRMS for C12H14NO4+ [M + H]+ 236.0917, found 236.0893.
The general procedure for the synthesis of compounds D1~7 [
27] is presented here.
To a solution of compounds B1~7 (2 mmol) in DMF (6 mL), anhydrous K2CO3 (0.83 g, 6 mmol) and dibromomethane (CH2Br2, 0.3 mL, 4 mol) were added and the mixture was heated at 120 °C under the nitrogen atmosphere for 2–4 h. When the reaction was complete, as determined by TLC analysis, the solution was cooled to room temperature and then partitioned between ethyl acetate (EA, 30 mL) and water (15 mL). The organic layer was washed with water (10 mL × 3); after drying by anhydrous sodium sulfate (Na2SO4), the mixture was concentrated to obtain the crude product and then this was purified by flash column chromatography on silica gel to obtain products D1~7 as solids in 83~91% yields.
8-bromo-4-methyl-[1,3]dioxolo[4,5-c]quinoline (D1): Pink solid, yield 89.7%, m.p., 97–99 °C. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 2.2 Hz, 1H), 7.80 (d, J = 9.1 Hz, 1H), 7.58 (dd, J = 9.1, 2.3 Hz, 1H), 6.25 (s, 2H), 2.62 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.4, 144.1, 143.8, 140.4, 131.3, 130.5, 122.2, 119.5, 116.5, 103.0, 19.3. HRMS for C11H9BrNO2+ [M + H]+ 265.9811, found 265.9818.
8-iodo-4-methyl-[1,3]dioxolo[4,5-c]quinoline(D2): White solid, yield 90.1%, m.p., 103–105 °C. 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 1.9 Hz, 1H), 7.76 (dd, J = 9.0, 2.0 Hz, 1H), 7.68 (d, J = 9.1 Hz, 1H), 6.25 (s, 2H), 2.63 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.2, 144.3, 144.0, 140.3, 136.6, 130.4, 128.9, 117.2, 103.1, 90.9, 19.3. HRMS for C11H9INO2+ [M + H]+ 313.9672, found 313.9651.
4,8-dimethyl-[1,3]dioxolo[4,5-c]quinoline (D3): Yellow solid, yield 93.7%, m.p., 93–95 °C. 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.7 Hz, 1H), 7.51 (dt, J = 2.0, 1.0 Hz, 1H), 7.36 (dd, J = 8.8, 2.0 Hz, 1H), 6.20 (s, 2H), 2.62 (s, 3H), 2.48 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 147.8, 144.0, 142.5, 139.7, 135.6, 130.3, 128.4, 118.5, 115.4, 102.6, 21.6, 19.2. HRMS for C12H12NO2+ [M + H]+ 202.0863, found 202.0848.
7-methoxy-4-methyl-[1,3]dioxolo[4,5-c]quinoline (D4): Yellow solid, yield 91.6%, m.p., 117–119 °C. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 9.1 Hz, 1H), 7.31 (d, J = 2.4 Hz, 1H), 7.10 (dd, J = 9.1, 2.4 Hz, 1H), 6.20 (s, 2H), 3.91 (s, 3H), 2.62 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 159.7, 148.9, 147.0, 143.1, 138.7, 121.0, 119.3, 110.15, 106.6, 102.5, 55.4, 19.2. HRMS for C12H12NO3+ [M + H]+ 218.0812, found 218.0811.
4-methyl-7-(trifluoromethyl)-[1,3]dioxolo[4,5-c]quinoline (D5): White solid, yield 84.1%, m.p., 107–109 °C. 1H NMR (400 MHz, CDCl3) δ 8.29 (s, 1H), 7.89 (d, J = 8.7 Hz, 1H), 7.60 (dd, J = 8.7, 1.7 Hz, 1H), 6.31 (s, 2H), 2.68 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 148.3, 145.4, 144.0, 141.2, 129.7 (q, J = 32.7 Hz), 126.7 (q, J = 4.5 Hz), 124.08 (d, J = 272.3 Hz), 121.56–120.54 (m, 2C) 116.9, 103.3, 19.4. HRMS for C12H9F3NO2+ [M + H]+ 256.0580, found 256.0570.
7,8-difluoro-4-methyl-[1,3]dioxolo[4,5-c]quinoline (D6): Pink solid, yield 83.2%, m.p., 104–106 °C. 1H NMR (400 MHz, CDCl3) δ 7.71 (dd, J = 11.7, 7.6 Hz, 1H), 7.46 (dd, J = 10.1, 8.4 Hz, 1H), 6.25 (s, 2H), 2.62 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 151.4 (dd, J = 252.2, 16.3 Hz), 149.8 (dd, J = 252.0, 16.4 Hz),148.3 (dd, J = 4.0, 2.6 Hz), 144.0 (d, J = 2.6 Hz), 142.3 (d, J = 11.4 Hz), 140.1 (d, J = 2.6 Hz), 115.2 (dd, J = 16.8, 1.5 Hz), 111.9 (d, J = 8.4 Hz), 105.5 (dd, J = 19.6, 1.5 Hz), 103.0, 19.2. HRMS for C11H8F2NO2+ [M + H]+ 224.0518, found 224.0485.
7,8-dimethoxy-4-methyl-[1,3]dioxolo[4,5-c]quinoline (D7): Yellow solid, yield 89.6%, m.p., 110–112 °C. 1H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 1.7 Hz, 1H), 6.94 (s, 1H), 6.18 (s, 2H), 3.98 (s, 6H), 2.59 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 146.6, 144.7, 143.0, 137.6, 135.5, 134.2, 105.2, 102.8, 97.6, 92.6, 51.3, 51.2, 14.1. HRMS for C13H14NO4+ [M + H]+ 248.0917, found 248.0881.
The general procedure for the synthesis of compounds D8~12 [
29] is presented here.
A mixture of Tetrakis(triphenylphosphine) palladium(Pd(PPh3)4, 0.05 mmol), anhydrous K2CO3 (0.69 g, 5 mmol), compounds D1 (0.26 g, 1 mmol), and aryl boronic acid (1 mmol) in 1,4-Dioxane (10 mL) was degassed by flushing with nitrogen. After being stirred at 100 °C for 10 h, the mixture was then partitioned between EA (30 mL) and water (10 mL). The organic layer was separated, washed with water, dried, and concentrated. The residue was then purified by column chromatography to give the coupled products D8~12 as solids in 50~66% yields.
4-methyl-8-phenyl-[1,3]dioxolo[4,5-c]quinoline (D8): White solid, yield 90.8%, m.p., 114–116 °C. 1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J = 9.0, 0.7 Hz, 1H), 7.96 (dd, J = 2.1, 0.7 Hz, 1H), 7.81 (dd, J = 8.9, 2.1 Hz, 1H), 7.74–7.67 (m, 2H), 7.51–7.43 (m, 2H), 7.41–7.34 (m, 1H), 6.25 (d, J = 0.8 Hz, 2H), 2.66 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 148.5, 144.8, 143.5, 140.3, 140.1, 138.3, 129.2, 128.9, 127.7, 127.6, 127.3, 117.5, 115.7, 102.8, 19.4. HRMS for C17H14NO2+ [M + H]+ 264.1019, found 264.1023.
4-methyl-8-(p-tolyl)-[1,3]dioxolo[4,5-c]quinoline (D9): White solid, yield 92.8%, m.p., 148–150 °C. 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 9.0 Hz, 1H), 7.93 (d, J = 2.0 Hz, 1H), 7.80 (dd, J = 8.9, 2.1 Hz, 1H), 7.63–7.56 (m, 2H), 7.31–7.26 (m, 2H), 6.24 (s, 2H), 2.65 (s, 3H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 148.4, 144.7, 143.3, 140.0, 138.2, 137.6, 137.4, 129.7, 129.1, 127.6, 127.1, 117.0, 115.7, 102.8, 21.2, 19.3. HRMS for C18H16NO2+ [M + H]+ 278.1176, found 278.1183.
8-(4-chlorophenyl)-4-methyl-[1,3]dioxolo[4,5-c]quinoline (D10): Yellow solid, yield 95.3%, m.p., 170–172 °C. 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.9 Hz, 1H), 7.90 (d, J = 2.1 Hz, 1H), 7.75 (dd, J = 8.9, 2.2 Hz, 1H), 7.61 (d, J = 8.6 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H), 6.26 (s, 2H), 2.66 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 148.5, 144.7, 143.8, 140.2, 138.7, 137.0, 133.9, 129.4, 129.1, 128.5, 127.2, 117.5, 115.6, 102.9, 19.3. HRMS for: C17H13ClNO2+ [M + H]+ 298.0629, found 298.0631.
8-(3,4-dimethoxyphenyl)-4-methyl-[1,3]dioxolo[4,5-c]quinoline (D11): White solid, yield 89.7%, m.p., 120–122 °C. 1H NMR (400 MHz, CDCl3) δ 8.03–7.97 (m, 1H), 7.92–7.88 (m, 1H), 7.79 (dd, J = 8.9, 2.1 Hz, 1H), 7.30–7.24 (m, 1H), 7.21 (d, J = 2.2 Hz, 1H), 6.98 (d, J = 8.3 Hz, 1H), 6.26 (s, 2H), 3.96 (d, J = 16.7 Hz, 6H), 2.66 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 149.3, 149.0, 148.3, 144.6, 143.3, 140.1, 138.1, 133.2, 129.1, 127.5, 119.7, 116.7, 115.7, 111.6, 110.5, 102.8, 56.0, 56.0, 19.3. HRMS for C19H18NO4+ [M + H]+ 324.1230, found 324.1245.
4-methyl-8-(thiophen-2-yl)-[1,3]dioxolo[4,5-c]quinoline (D12): White solid, yield 87.2%, m.p., 130–132 °C. 1H NMR (400 MHz, Chloroform-d) δ 7.98–7.91 (m, 2H), 7.81 (dd, J = 9.1, 2.0 Hz, 1H), 7.43 (dd, J = 3.6, 1.1 Hz, 1H), 7.33 (dd, J = 5.1, 1.1 Hz, 1H), 7.11 (dd, J = 5.1, 3.6 Hz, 1H), 6.25 (s, 2H), 2.64 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 148.4, 144.7, 143.6, 143.4, 140.3, 131.6, 129.3, 128.3, 126.5, 125.6, 124.0, 115.8, 115.7, 102.9, 19.3. HRMS for C15H12NO2S+ [M + H]+ 270.0583, found 270.0583.
The general procedure for the synthesis of compounds C8~12 [
30] is presented here.
A suspension of compounds D8~12 (1 mmol) in 5 mL of diluted hydrochloric acid (HCl/H2O, 3 mol/L) was heated to 75 °C for 0.5 h. The suspension turned into a clear solution. The solution continued heating and refluxed for 6 h. A crude solid precipitate was observed. Then, the mixture was adjusted to pH 7 with saturated sodium carbonate solution. The precipitate was filtered, washed with water (3 mL), ethanol (3 mL), and dichloromethane (4 mL), and dried under vacuum to provide products C8~12 as solids in 70~84% yields.
3-hydroxy-2-methyl-6-phenylquinolin-4(1H)-one (C8): White solid, yield 51.4%, m.p., > 300 °C 1H NMR (400 MHz, DMSO-d6) δ 8.53 (s, 1H), 8.11 (q, J = 8.5 Hz, 2H), 7.83 (d, J = 7.6 Hz, 2H), 7.54 (t, J = 7.5 Hz, 2H), 7.44 (t, J = 7.2 Hz, 1H), 2.70 (s, 2H). 13C NMR (150 MHz, DMSO-d6) δ 157.6, 147.0, 139.0, 138.6, 136.9, 134.9, 131.0, 129.7, 128.8, 127.6, 120.4, 120.3, 120.2, 16.3. HRMS for C16H14NO2+ [M + H]+ 252.1019, found 252.1022.
3-hydroxy-2-methyl-6-(p-tolyl)quinolin-4(1H)-one (C9): White solid, yield 59.9%, m.p., > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 14.39 (s, 1H), 8.49 (d, J = 1.9 Hz, 1H), 8.10 (dd, J = 8.9, 2.0 Hz, 1H), 8.02 (d, J = 8.9 Hz, 1H), 7.82–7.61 (m, 2H), 7.34 (d, J = 8.0 Hz, 2H), 2.68 (s, 3H), 2.38 (s, 3H). 13C NMR (150 MHz, DMSO-d6) δ 144.0, 138.2, 137.7, 137.3, 136.3, 135.2, 130.6, 130.3, 127.3, 120.9, 120.1, 120.0, 21.2, 16.0. HRMS for C17H16NO2+ [M + H]+ 266.1176, found 266.1153.
6-(4-chlorophenyl)-3-hydroxy-2-methylquinolin-4(1H)-one (C10): White solid, yield 50.7%, m.p., > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.33 (s, 1H), 7.88 (d, J = 8.6 Hz, 1H), 7.77 (d, J = 8.1 Hz, 2H), 7.61 (d, J = 8.7 Hz, 1H), 7.54 (d, J = 8.2 Hz, 2H), 2.39 (s, 3H). 13C NMR (150 MHz, DMSO-d6) δ 144.9, 138.0, 137.3, 136.4, 135.3, 133.6, 130.5, 129.6, 129.2, 120.8, 120.7, 120.3, 16.1. HRMS for C16H13ClNO2+ [M + H]+ 286.0629, found 286.0633.
6-(3,4-dimethoxyphenyl)-3-hydroxy-2-methylquinolin-4 (1H)-one (C11): White solid, yield 61.3%, m.p., > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 14.71 (s, 1H), 8.55 (d, J = 2.0 Hz, 1H), 8.15 (dd, J = 8.9, 2.0 Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 2.2 Hz, 1H), 7.36 (dd, J = 8.3, 2.2 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 3.90 (s, 3H), 3.83 (s, 3H), 2.71 (s, 3H). 13C NMR (150 MHz, DMSO-d6) δ 157.7, 149.8, 149.7, 146.2, 138.3, 137.0, 134.7, 131.6, 130.8, 120.5, 120.2, 120.0, 119.4, 112.7, 111.0, 56.5, 56.1, 16.2. HRMS for C18H19NO4+ [M + H]+ 312.1230, found 312.1231.
3-hydroxy-2-methyl-6-(thiophen-2-yl)quinolin-4(1H)-one (C12): White solid, yield 66.6%, m.p., > 300 °C. 1H NMR (400 MHz, DMSO-d6) δ 14.40 (s, 1H), 8.45–8.40 (m, 1H), 8.16–8.07 (m, 1H), 8.01–7.96 (m, 1H), 7.70 (d, J = 3.7 Hz, 1H), 7.66 (d, J = 4.9 Hz, 1H), 7.21 (dd, J = 5.1, 3.6 Hz, 1H), 2.66 (s, 3H). 13C NMR (150 MHz, DMSO-d6) δ 158.8, 144.3, 142.6, 137.5, 135.2, 131.4, 129.4, 129.3, 127.4, 125.6, 121.1, 120.4, 118.7, 15.9. HRMS for C14H12NO2S+ [M + H]+ 258.0583, found 258.0553.