7-CHLORO-3,4-DIHYDRO-2H-ISOQUINOLIN-1-ONE

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

実験手順: 7-Chloro-3,4-dihydroisoquinolin-1(2H)-one (I-1d: 100 mg, 0.552 mmol) was reacted with 3-bromo-4-ethyl pyridine (133.5 mg, 0.718 mmol), 1,4-dioxane (5 mL), copper iodide (10.48 mg, 0.0555 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (7.8 mg, 0.055 mmol) and potassium phosphate (351 mg, 1.657 mmol for 48 hours at 120° C. to afford the crude product. Purification by column chromatography on silica gel (50% ethyl acetate in hexane), followed by preparative HPLC afforded 25 mg of the product (15.72% yield). to afford the crude product Purification by column chromatography on silica gel (50% ethyl acetate in hexane)

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

実験手順: 7-Chloro-3,4-dihydroisoquinolin-1(2H)-one (I-1d: 100 mg, 0.552 mmol) was reacted with 4-cyclopropyl-3-iodopyridine (I-73c: 162 mg, 0.662 mmol), 1,4-dioxane (5 mL), copper iodide (31 mg, 0.165 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (8 mg, 0.055 mmol) and potassium phosphate (351 mg, 1.657 mmol for 48 hours at 120° C. to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCl3) afforded 42 mg of the product (25.45% yield). to afford the crude product Purification by column chromatography on silica gel (2% methanol in CHCl3)

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

実験手順: Using analogous reaction conditions as described in Example 1, 7-chloro-3,4-dihydro-2H-isoquinolin-1-one (I-1d: 150 mg, 0.824 mmol) was reacted with 3-iodo-4-methyl-pyridine (216 mg, 0.989 mmol), 1,4-dioxane (10 mL), copper iodide (15.69 mg, 0.0824 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (35.10 mg, 0.2472 mmol) and potassium phosphate (524 mg, 2.472 mmol) to afford the crude product. Purification by column chromatography on silica gel (1% methanol in CHCl3) afforded 70 mg of the product (31.25% yield). reaction conditions to afford the crude product Purification by column chromatography on silica gel (1% methanol in CHCl3)

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Copper iodide (15.6 mg, 0.0824 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (28.3 mg, 0.2472 mmol) and potassium phosphate (437.3 mg, 2.0604 mmol) were added to 1,4-dioxane (20 mL) degassed with argon for 30 minutes. The reaction mixture was purged with argon for a further 20 minutes followed by the addition of 7-chloro-3,4-dihydro-2H-isoquinolin-1-one (I-1d: 150 mg, 0.82417 mmol) and 3-bromo-pyridine (88.9 mL, 0.9065 mmol). The reaction mixture was heated to reflux at 110° C. for 12 hours. The reaction was monitored by TLC (10% methanol in CHCl3). The reaction mixture was filtered and the filtrate was concentrated. Purification by column chromatography on silica gel (10% methanol in CHCl3) afforded 90 mg of the product (42.2% yield). degassed with argon for 30 minutes The reaction mixture was purged with argon for a further 20 minutes The reaction mixture was heated The reaction mixture was filtered the filtrate was concentrated Purification by column chromatography on silica gel (10% methanol in CHCl3)

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

実験手順: P2O5 (3.1 g, 0.0495 mmol) was added to a stirred solution of [2-(4-chloro-phenyl)-ethyl]-carbamic acid ethyl ester (2.5 g, 0.01097 mmol) in POCl3 (10 mL) The resulting mixture was heated to reflux for 3 hours. The reaction was monitored by TLC (10% methanol in DCM). The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The concentrate was quenched with chilled water, basified with NaHCO3 solution and extracted with ethylacetate. The organic layer was washed with water, brine solution, dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography on silica gel (10% methanol in CHCl3) afforded 500 mg of the product (26.3% yield). was heated to reflux for 3 hours concentrated under reduced pressure The concentrate was quenched with chilled water extracted with ethylacetate The organic layer was washed with water, brine solution dried over Na2SO4 concentrated under reduced pressure Purification by column chromatography on silica gel (10% methanol in CHCl3)