6,7-二氯-3,4-二氢-2H-异喹啉-1-one

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

实验步骤: Using an analogous procedure and workup as described for the preparation of Example 1A above, 6,7-dichloro-3,4-dihydroisoquinolin-1(2H)-one (I-55d: 100 mg, 0.463 mmol) was reacted with 3-bromo-4-(trifluoromethyl)pyridine (115 mg, 0.509 mmol), 1,4-dioxane (3 mL), copper iodide (7 mg, 0.046 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (20 mg, 0.1388 mmol) and potassium phosphate (245 mg, 1.157 mmol) in a sealed tube at 120° C. for 16 hours to afford the crude product. Purification by column chromatography on silica gel (20% ethylacetate in hexane) afforded 14 mg of the product (8.3% yield). to afford the crude product Purification by column chromatography on silica gel (20% ethylacetate in hexane)

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

实验步骤: Using an analogous procedure and workup as described for the preparation of intermediate I-1d above, ethyl 3,4-dichlorophenethylcarbamate (I-55c: 6 g, 22.989 mmol) in POCl3 (60 mL) was reacted with P2O5 (6.52 g, 45.977 mmol) at 120° C. for 1 hour to afford the crude product. Purification by column chromatography on silica gel (30% ethylacetate in hexane) afforded 1.01 g of the product. LCMS: 53.61%, m/z=216.0 (M+1) workup as described for the preparation of intermediate I-1d above to afford the crude product Purification by column chromatography on silica gel (30% ethylacetate in hexane)

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

实验步骤: Using an analogous reaction conditions as described in example 1, 6,7-dichloro-3,4-dihydro-2H-isoquinolin-1-one (I-41d: 0.15 g, 0.6944 mmol) was reacted with 3-iodo-4-methyl-pyridine (0.152 g, 0.6944 mmol), 1,4-dioxane (20 mL), copper iodide (0.013 g, 0.0494 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (0.032 mL, 0.2083 mmol) and potassium phosphate (0.368 g, 1.736 mmol) to afford the crude product. Purification by preparative HPLC afforded 18 mg of the product (8.4% yield). an analogous reaction conditions to afford the crude product Purification by preparative HPLC

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

实验步骤: Using an analogous reaction procedure and workup as described in Example 1, [2-(3,4-dichloro-phenyl)-ethyl]-carbamic acid ethyl ester (I-41c: 3.5 g, 13.409 mmol) in POCl3 (35 mL) was reacted with P2O5 (3.80 g, 26.819 mmol) at 120° C. for 1 hour to afford the crude product. Purification by column chromatography on silica gel (30% ethylacetate in hexane) afforded 0.350 g of the crude product which was used in the next step without further purification. an analogous reaction procedure to afford the crude product Purification by column chromatography on silica gel (30% ethylacetate in hexane)