ethyl (3aR,6aR)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[2,3-c]pyrrole-5-carboxylate

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(4′-Bromobiphenyl-4-yl)pyridazin-3(2H)-one (1.92 g, 5.86 mmol), palladium(II) acetate (0.158 g, 0.234 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.407 g, 0.703 mmol) and cesium carbonate (3.06 g, 9.38 mmol) were suspended in 25 mL of THF. A solution of (3aR,6aR)-ethyl hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate in 10 mL of THF was added and the mixture was heated at 70° C. under N2 for 20 hours. The mixture was allowed to cool to ambient temperature, diluted with 70 mL of EtOAc, and filtered through a ¼ pad of Celite®. The Celite® pad was washed with an additional 70 mL of EtOAc and the filtrate was absorbed on silica gel and chromatographed (eluting with 0-40% EtOAc in DCM) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (dd, J=3.7, 1.7 Hz, 1H), 7.64 (s, 4H), 7.53 (d, J=8.8 Hz, 2H), 7.25 (dd, J=9.8, 3.4 Hz, 1H), 7.07 (dd, J=9.5, 1.7 Hz, 1H), 6.64 (d, J=8.5 Hz, 2H), 4.20-4.32 (m, 1H), 4.12 (q, J=7.5 Hz, 2H), 3.70-3.81(m, 1H), 3.59-3.69 (m, 2H), 3.48-3.58 (m, 1H), 3.36-3.48 (m, 2H), 2.99-3.10 (m, 1H), 2.20 (ddd, J=13.0, 7.3 Hz, 1H), 1.95 (ddd, J=12.9, 6.4 Hz, 1H), 1.24 (t, J=7.1 Hz, 3H). MS (ESI+) m/z 431(M+H)+. to cool to ambient temperature filtered through a ¼ pad of Celite® The Celite® pad was washed with an additional 70 mL of EtOAc the filtrate was absorbed on silica gel chromatographed (eluting with 0-40% EtOAc in DCM)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The catalyst solution was added to the vessel containing the 4,4′-dibromobiphenyl, cesium carbonate, and the product of Example 41C and the mixture was heated to 98° C. for 12 hours. The mixture was cooled to 20° C. and 80 g of dichloromethane was added. The resulting mixture was stirred and then filtered to remove the catalyst. The resulting solution was concentrated under reduced pressure and the residue was purified by column chromatography to yield 5.65 g of the title compound. The catalyst solution was added to the vessel filtered to remove the catalyst The resulting solution was concentrated under reduced pressure the residue was purified by column chromatography

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(4′-Bromobiphenyl-4-yl)pyridazin-3(2H)-one (1.92 g, 5.86 mmol), palladium(II) acetate (0.158 g, 0.234 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.407 g, 0.703 mmol) and cesium carbonate (3.06 g, 9.38 mmol) were suspended in 25 mL of THF. A solution of (3aR,6aR)-ethyl hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate in 10 mL of THF was added and the mixture was heated at 70° C. under N2 for 20 hours. The mixture was allowed to cool to ambient temperature, diluted with 70 mL of EtOAc, and filtered through a ¼ pad of Celite®. The Celite® pad was washed with an additional 70 mL of EtOAc and the filtrate was absorbed on silica gel and chromatographed (eluting with 0-40% EtOAc in DCM) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (dd, J=3.7, 1.7 Hz, 1H), 7.64 (s, 4H), 7.53 (d, J=8.8 Hz, 2H), 7.25 (dd, J=9.8, 3.4 Hz, 1H), 7.07 (dd, J=9.5, 1.7 Hz, 1H), 6.64 (d, J=8.5 Hz, 2H), 4.20-4.32 (m, 1H), 4.12 (q, J=7.5 Hz, 2H), 3.70-3.81(m, 1H), 3.59-3.69 (m, 2H), 3.48-3.58 (m, 1H), 3.36-3.48 (m, 2H), 2.99-3.10 (m, 1H), 2.20 (ddd, J=13.0, 7.3 Hz, 1H), 1.95 (ddd, J=12.9, 6.4 Hz, 1H), 1.24 (t, J=7.1 Hz, 3H). MS (ESI+) m/z 431(M+H)+. to cool to ambient temperature filtered through a ¼ pad of Celite® The Celite® pad was washed with an additional 70 mL of EtOAc the filtrate was absorbed on silica gel chromatographed (eluting with 0-40% EtOAc in DCM)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The catalyst solution was added to the vessel containing the 4,4′-dibromobiphenyl, cesium carbonate, and the product of Example 41C and the mixture was heated to 98° C. for 12 hours. The mixture was cooled to 20° C. and 80 g of dichloromethane was added. The resulting mixture was stirred and then filtered to remove the catalyst. The resulting solution was concentrated under reduced pressure and the residue was purified by column chromatography to yield 5.65 g of the title compound. The catalyst solution was added to the vessel filtered to remove the catalyst The resulting solution was concentrated under reduced pressure the residue was purified by column chromatography

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(4′-Bromobiphenyl-4-yl)pyridazin-3(2H)-one (1.92 g, 5.86 mmol), palladium(II) acetate (0.158 g, 0.234 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.407 g, 0.703 mmol) and cesium carbonate (3.06 g, 9.38 mmol) were suspended in 25 mL of THF. A solution of (3aR,6aR)-ethyl hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate in 10 mL of THF was added and the mixture was heated at 70° C. under N2 for 20 hours. The mixture was allowed to cool to ambient temperature, diluted with 70 mL of EtOAc, and filtered through a ¼″ pad of Celite®. The Celite® pad was washed with an additional 70 mL of EtOAc and the filtrate was absorbed on silica gel and chromatographed (eluting with 0-40% EtOAc in DCM) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (dd, J=3.7, 1.7 Hz, 1H), 7.64 (s, 4H), 7.53 (d, J=8.8 Hz, 2H), 7.25 (dd, J=9.8, 3.4 Hz, 1H), 7.07 (dd, J=9.5, 1.7 Hz, 1H), 6.64 (d, J=8.5 Hz, 2H), 4.20-4.32 (m, 1H), 4.12 (q, J=7.5 Hz, 2H), 3.70-3.81 (m, 1H), 3.59-3.69 (m, 2H), 3.48-3.58 (m, 1H), 3.36-3.48 (m, 2H), 2.99-3.10 (m, 1H), 2.20 (ddd, J=13.0, 7.3 Hz, 1H), 1.95 (ddd, J=12.9, 6.4 Hz, 1H), 1.24 (t, J=7.1 Hz, 3H). MS (ESI+) m/z 431 (M+H)+. to cool to ambient temperature filtered through a ¼″ pad of Celite® The Celite® pad was washed with an additional 70 mL of EtOAc the filtrate was absorbed on silica gel chromatographed (eluting with 0-40% EtOAc in DCM)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The catalyst solution was added to the vessel containing the 4,4′-dibromobiphenyl, cesium carbonate, and the product of Example 41C and the mixture was heated to 98° C. for 12 hours. The mixture was cooled to 20° C. and 80 g of dichloromethane was added. The resulting mixture was stirred and then filtered to remove the catalyst. The resulting solution was concentrated under reduced pressure and the residue was purified by column chromatography to yield 5.65 g of the title compound. The catalyst solution was added to the vessel filtered to remove the catalyst The resulting solution was concentrated under reduced pressure the residue was purified by column chromatography

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-(4′-Bromobiphenyl-4-yl)pyridazin-3(2H)-one (1.92 g, 5.86 mmol), palladium(II) acetate (0.158 g, 0.234 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.407 g, 0.703 mmol) and cesium carbonate (3.06 g, 9.38 mmol) were suspended in 25 mL of THF. A solution of (3aR,6aR)-ethyl hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate in 10 mL of THF was added and the mixture was heated at 70° C. under N2 for 20 hours. The mixture was allowed to cool to ambient temperature, diluted with 70 mL of EtOAc, and filtered through a ¼ pad of Celite®. The Celite® pad was washed with an additional 70 mL of EtOAc and the filtrate was absorbed on silica gel and chromatographed (eluting with 0-40% EtOAc in DCM) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (dd, J=3.7, 1.7 Hz, 1H), 7.64 (s, 4H), 7.53 (d, J=8.8 Hz, 2H), 7.25 (dd, J=9.8, 3.4 Hz, 1H), 7.07 (dd, J=9.5, 1.7 Hz, 1H), 6.64 (d, J=8.5 Hz, 2H), 4.20-4.32 (m, 1H), 4.12 (q, J=7.5 Hz, 2H), 3.70-3.81(m, 1H), 3.59-3.69 (m, 2H), 3.48-3.58 (m, 1H), 3.36-3.48 (m, 2H), 2.99-3.10 (m, 1H), 2.20 (ddd, J=13.0, 7.3 Hz, 1H), 1.95 (ddd, J=12.9, 6.4 Hz, 1H), 1.24 (t, J=7.1 Hz, 3H). MS (ESI+) m/z 431(M+H)+. to cool to ambient temperature filtered through a ¼ pad of Celite® The Celite® pad was washed with an additional 70 mL of EtOAc the filtrate was absorbed on silica gel chromatographed (eluting with 0-40% EtOAc in DCM)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The catalyst solution was added to the vessel containing the 4,4′-dibromobiphenyl, cesium carbonate, and the product of Example 41C and the mixture was heated to 98° C. for 12 hours. The mixture was cooled to 20° C. and 80 g of dichloromethane was added. The resulting mixture was stirred and then filtered to remove the catalyst. The resulting solution was concentrated under reduced pressure and the residue was purified by column chromatography to yield 5.65 g of the title compound. The catalyst solution was added to the vessel filtered to remove the catalyst The resulting solution was concentrated under reduced pressure the residue was purified by column chromatography