7-chloro-3,4-dihydro-1H-quinolin-2-one

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of the product from step (ii) (0.174 g) and sodium hydride (60% wt. disp. oil, 0.039 g) in DMF (10 ml) was stirred at 50° C. for 1 hour. The product from example 3 step (vi)-(vii) (0.200 g) was added and the mixture was refluxed at 90° C. for 3 hours. The mixture was partitioned between 2M sodium hydroxide and diethyl ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate and the organic layer dried and concentrated under reduced pressure to give an oil. The residue was purified using RP prep HPLC. Yield 0.061 g The mixture was partitioned between 2M sodium hydroxide and diethyl ether extracted with ethyl acetate the organic layer dried concentrated under reduced pressure to give an oil The residue was purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the product from step (i) (4.95 g) and 5% platinum on carbon (0.400 g) and a few drops of 2M hydrochloric acid in ethyl acetate (30 ml) was hydrogenated under a pressure of 3 bar. The catalyst was removed by filtration through celite and the filtrate was evaporated under reduced pressure to a brown solid, which was triturated with diethyl ether to give a pink solid. Yield 1.28 g The catalyst was removed by filtration through celite the filtrate was evaporated under reduced pressure to a brown solid, which was triturated with diethyl ether to give a pink solid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.665 millimols, i.e. a yield of 90% relative to the 7-chloro-1,2,3,4-tetrahydroquinolinone converted, and a yield of 91.2% relative to the 1-diethylamino-4-aminopentane converted, and

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To solution of 7-chloro-3,4-dihydroquinolin-2(1H)-one (110-1; 2.92 g, 0.016 mol) in N,N-dimethylformamide (30 mL), was added N-bromosuccinimide (3.14 g, 0.0176 mol) portion-wise at room temperature. The resulting mixture was stirred at room temperature for 16 h. After 16 h, the reaction mixture was diluted with cold water, solid get precipitated, filtered the solid, washed the solid with water and dried under reduced pressure to afford the compound. 1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 7.56 (s, 1H), 7.01 (s, 1H), 2.87-2.84 (t, J=7.2 Hz, 2H), 2.45-2.41 (t, J=7.6 Hz, 2H); MS (M+1): 259.9. After 16 h get precipitated filtered the solid washed the solid with water dried under reduced pressure to afford the compound

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-chloro-2-iodoaniline (14.0 g, 0.0552 mol) in dimethyl sulphoxide, ethyl acrylate (30.38 mL, 0.276 mol) and n-tributyltinhydride (22.3 mL, 0.0828 mol), AIBN (3.6 g, 0.022 mol) was added at room temperature. The reaction mixture was heated to 120° C. and stirred for 16 h. The reaction mixture was cooled to room temperature; the reaction mixture was diluted with water. The aqueous phase was extracted with ethyl acetate (3×500 mL), the combined organic layer was washed with cold water, saturated aqueous sodium chloride solution and dried over sodium sulphate, the solvent was evaporated under vacuum and the residue was purified with silica gel (60-120 mesh) silica gel column chromatography by 0-20% ethyl acetate in hexane to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 7.17-7.15 (d, J=7.6 Hz, 1H), 6.93-6.91 (d, J=8.0 Hz, 1H), 6.85 (s, 1H), 2.85-2.81 (t, J=7.2 Hz, 2H), 2.44-2.41 (t, J=8 Hz, 2H); MS (M+1): 181.9. The reaction mixture was cooled to room temperature The aqueous phase was extracted with ethyl acetate (3×500 mL) the combined organic layer was washed with cold water, saturated aqueous sodium chloride solution dried over sodium sulphate the solvent was evaporated under vacuum the residue was purified with silica gel (60-120 mesh) silica gel column chromatography by 0-20% ethyl acetate in hexane

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of the product from step (ii) (0.174 g) and sodium hydride (60% wt. disp. oil, 0.039 g) in DMF (10 ml) was stirred at 50° C. for 1 hour. The product from example 3 step (vi)-(vii) (0.200 g) was added and the mixture was refluxed at 90° C. for 3 hours. The mixture was partitioned between 2M sodium hydroxide and diethyl ether. The aqueous layer was acidified with 2M hydrochloric acid, extracted with ethyl acetate and the organic layer dried and concentrated under reduced pressure to give an oil. The residue was purified using RP prep HPLC. Yield 0.061 g The mixture was partitioned between 2M sodium hydroxide and diethyl ether extracted with ethyl acetate the organic layer dried concentrated under reduced pressure to give an oil The residue was purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the product from step (i) (4.95 g) and 5% platinum on carbon (0.400 g) and a few drops of 2M hydrochloric acid in ethyl acetate (30 ml) was hydrogenated under a pressure of 3 bar. The catalyst was removed by filtration through celite and the filtrate was evaporated under reduced pressure to a brown solid, which was triturated with diethyl ether to give a pink solid. Yield 1.28 g The catalyst was removed by filtration through celite the filtrate was evaporated under reduced pressure to a brown solid, which was triturated with diethyl ether to give a pink solid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3.665 millimols, i.e. a yield of 90% relative to the 7-chloro-1,2,3,4-tetrahydroquinolinone converted, and a yield of 91.2% relative to the 1-diethylamino-4-aminopentane converted, and