6-bromo-8-chloro-3,4-dihydroquinolin-2(1H)-one

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 6-bromo-8-chloro-3,4-dihydro-1H-quinolin-2-one (7.0 g, 26.9 mmol) in DMF (100 mL) was treated with potassium tert-butoxide (6.0 g, 53.8 mmol) at 0° C. in portions. The resulting mixture was stirred at 0° C. for 30 min before methyl iodide (5.0 g, 35.0 mmol) was added. After stirring for 12 h, the reaction mixture was treated with water, extracted with EtOAc, washed with water and brine in sequence, and dried over anhy. Na2SO4. After removal of solvents under reduced pressure, the crude product (3.3 g, 45% yield) was obtained as a white solid. was added extracted with EtOAc washed with water and brine in sequence dried over anhy After removal of solvents under reduced pressure

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flame-dried 500-mL flask equipped with a magnetic stirring bar was charged with N-(4-bromo-2-chloro-phenyl)-3-chloro-propionamide (29.7 g, 0.1 mol) and aluminium chloride (53.3 g, 0.4 mol). In a pre-heated oil bath, the flask was heated at 140° C. for 1 hr. After cooling to room temperature, the mixture was treated with ice-water slowly and extracted with EtOAc. The organic layer was washed with water and brine in sequence, dried over anhy. Na2SO4, filtered, and concentrated in vacuo. The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane) to afford the title compound (7.0 g, 27% yield) as a white solid. A flame-dried 500-mL flask equipped with a magnetic stirring bar After cooling to room temperature extracted with EtOAc The organic layer was washed with water and brine in sequence dried over anhy Na2SO4, filtered concentrated in vacuo The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane)

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flame-dried 500-mL flask equipped with a magnetic stirring bar was charged with N-(4-bromo-2-chloro-phenyl)-3-chloro-propionamide (29.7 g, 0.1 mol) and aluminium chloride (53.3 g, 0.4 mol). In a pre-heated oil bath, the flask was heated at 140° C. for 1 hr. After cooling to room temperature, the mixture was treated with ice-water slowly and extracted with EtOAc. The organic layer was washed with water and brine in sequence, dried over anhy. Na2SO4, filtered, and concentrated in vacuo. The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane) to afford the title compound (7.0 g, 27% yield) as a white solid. A flame-dried 500-mL flask equipped with a magnetic stirring bar After cooling to room temperature extracted with EtOAc The organic layer was washed with water and brine in sequence dried over anhy Na2SO4, filtered concentrated in vacuo The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 6-bromo-8-chloro-3,4-dihydro-1H-quinolin-2-one (7.0 g, 26.9 mmol) in DMF (100 mL) was treated with potassium tert-butoxide (6.0 g, 53.8 mmol) at 0° C. portionwise. The resulting mixture was stirred at 0° C. for 30 minutes before methyl iodide (5.0 g, 35.0 mmol) was added. After stirred for 12 hours, the reaction mixture was treated with water, extracted with EtOAc, washed with water and brine in sequence, and dried over anhydrous Na2SO4. After removal of solvent under reduced pressure, the crude product (3.3 g, 45%) was obtained as a white solid. was added extracted with EtOAc washed with water and brine in sequence dried over anhydrous Na2SO4 After removal of solvent under reduced pressure

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flame-dried 500-mL flask equipped with a magnetic stirring bar was charged with N-(4-bromo-2-chloro-phenyl)-3-chloro-propionamide (29.7 g, 0.1 mol) and aluminium chloride (53.3 g, 0.4 mol). In a pre-heated oil bath, the flask was heated at 140° C. for 1 hour. After cooling to room temperature, the mixture was treated slowly with ice-water and extracted with EtOAc. The organic layer was washed with water and brine in sequence, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane) to afford the title compound (7.0 g, 27%) as a white solid. A flame-dried 500-mL flask equipped with a magnetic stirring bar After cooling to room temperature extracted with EtOAc The organic layer was washed with water and brine in sequence dried over anhydrous Na2SO4 filtered concentrated in vacuo The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane)

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 6-bromo-7-fluoro-3,4-dihydroquinolin-2(1H)-one (122-3; 3 g, 0.0012 mol) in N,N-dimethylformamide (30 mL) was added N-chlorosuccinimide in N,N-dimethylformamide (3 mL) (1.4 g, 0.0105 mol) at 70° C. drop wise over a period of 2 h. Reaction mass was allowed to stir at 70° C. for 14 h. The reaction mixture was cooled and diluted with ice cold water. The precipitated solid was filtered and dried to obtain title compound. MS (M−1): 278.12. Reaction mass The reaction mixture was cooled diluted with ice cold water The precipitated solid was filtered dried

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 6-bromo-8-chloro-3,4-dihydroquinolin-2(1H)-one (80-1; 10 g, 0.038 mol) in toluene (130 mL) was added Lawesson's reagent (7.7 g, 0.019 mol). Reaction mass was refluxed at 100° C. for 3 h. The reaction mixture was concentrated and directly purified by silica gel column chromatography to obtain title compound. 1H NMR (400 MHz, DMSO-d6) δ: 11.25 (s, 1H), 7.61-7.60 (d, J=2.4 Hz, 1H), 7.48 (s, 1H), 2.96-2.93 (m, 2H), 2.85-2.81 (m, 2H). MS (M+2): 277. Reaction mass The reaction mixture was concentrated directly purified by silica gel column chromatography

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 6-bromo-3,4-dihydroquinolin-2(1H)-one (74-3; 20 g, 0.088 mol) in N,N-dimethylformamide (200 mL) was added N-chlorosuccinimide portion wise (17.7 g, 0.132 mol) at 80° C. Reaction mass was allowed to stir at 80° C. for 2 h. The reaction mixture was cooled and diluted with ice cold water. The precipitated solid filtered and dried to obtain title compound. 1H NMR (400 MHz, DMSO-d6) δ: 9.61 (bs, 1H), 7.52-7.51 (d, J=1.6 Hz, 1H), 7.41 (s, 1H), 2.93-2.90 (t, J=8 Hz, 2H). MS (M+1); 261.2. Reaction mass The reaction mixture was cooled diluted with ice cold water The precipitated solid filtered dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 6-bromo-8-chloro-3,4-dihydro-1H-quinolin-2-one (7.0 g, 26.9 mmol) in DMF (100 mL) was treated with potassium tert-butoxide (6.0 g, 53.8 mmol) at 0° C. in portions. The resulting mixture was stirred at 0° C. for 30 min before methyl iodide (5.0 g, 35.0 mmol) was added. After stirring for 12 h, the reaction mixture was treated with water, extracted with EtOAc, washed with water and brine in sequence, and dried over anhy. Na2SO4. After removal of solvents under reduced pressure, the crude product (3.3 g, 45% yield) was obtained as a white solid. was added extracted with EtOAc washed with water and brine in sequence dried over anhy After removal of solvents under reduced pressure

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flame-dried 500-mL flask equipped with a magnetic stirring bar was charged with N-(4-bromo-2-chloro-phenyl)-3-chloro-propionamide (29.7 g, 0.1 mol) and aluminium chloride (53.3 g, 0.4 mol). In a pre-heated oil bath, the flask was heated at 140° C. for 1 hr. After cooling to room temperature, the mixture was treated with ice-water slowly and extracted with EtOAc. The organic layer was washed with water and brine in sequence, dried over anhy. Na2SO4, filtered, and concentrated in vacuo. The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane) to afford the title compound (7.0 g, 27% yield) as a white solid. A flame-dried 500-mL flask equipped with a magnetic stirring bar After cooling to room temperature extracted with EtOAc The organic layer was washed with water and brine in sequence dried over anhy Na2SO4, filtered concentrated in vacuo The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane)