9-bromo-5,11-dihydrobenzo[b][1,4]benzodiazepin-6-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of Example 9 (116 mg, 0.4 mmol), 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (150 mg, 0.6 mmol), Pd(PPh3)4 (23 mg, 0.02 mmol), and CsF (121 mg, 0.8 mmol) in DME (20 mL) and methanol (10 mL) was heated to reflux for 16 hours, cooled to room temperature, and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 0.108 g (81%) of the desired product. MS (DCI) m/e 333 (M+H)+, 350 (M+NH4)+; 1H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.02 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.24 (d, J=1.8 Hz, 1H), 7.15-7.18 (m, 2H), 7.08 (dd, J=8.1, 1.5 Hz, 1H), 6.97-7.02 (m, 5H), 3.86 (s, 3H). to reflux for 16 hours partitioned between ethyl acetate and water The organic layer was washed with brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-chlorobenzoic acid (2.35 g, 10 mmol), 1,2-benzenediamine (1.08 g, 10 mmol) and copper (0.63 g, 10 mmol) in chlorobenzene (150 mL) was heated to reflux for 48 hours and filtered. The filter cake was washed with ethyl acetate several times. The combined filtrates were concentrated under vacuum and the residue was purified by flash column chromatography on silica gel with 8:2 hexanes/ethyl acetate to provide 1.20 g (22%) of the desired product. MS (DCI) m/e 289 (M+H)+, 307 (M+NH4)+; 1H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.02 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.24 (d, J=1.8 Hz, 1H), 7.06 (dd, J=8.4, 1.8 Hz, 1H), 6.92-6.95 (m, 5H). was heated to reflux for 48 hours filtered The filter cake was washed with ethyl acetate several times The combined filtrates were concentrated under vacuum the residue was purified by flash column chromatography on silica gel with 8:2 hexanes/ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-chlorobenzoic acid (2.35 g, 10 mmol), 1,2-benzenediamine (1.08 g, 10 mmol) and copper (0.63 g, 10 mmol) in chlorobenzene (150 mL) was heated to reflux for 48 hours and filtered. The filter cake was washed with ethyl acetate several times. The combined filtrates were concentrated under vacuum and the residue was purified by flash column chromatography on silica gel with 8:2 hexanes/ethyl acetate to provide 1.20 g (22%) of the desired product. MS (DCI) m/e 289 (M+H)+, 307 (M+NH4)+; 1H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.02 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.24 (d, J=1.8 Hz, 1H), 7.06 (dd, J=8.4, 1.8 Hz, 1H), 6.92-6.95 (m, 5H). was heated to reflux for 48 hours filtered The filter cake was washed with ethyl acetate several times The combined filtrates were concentrated under vacuum the residue was purified by flash column chromatography on silica gel with 8:2 hexanes/ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of Example 9 (116 mg, 0.4 mmol), 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (150 mg, 0.6 mmol), Pd(PPh3)4 (23 mg, 0.02 mmol), and CsF (121 mg, 0.8 mmol) in DME (20 mL) and methanol (10 mL) was heated to reflux for 16 hours, cooled to room temperature, and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 0.108 g (81%) of the desired product. MS (DCI) m/e 333 (M+H)+, 350 (M+NH4)+; 1H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.02 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.24 (d, J=1.8 Hz, 1H), 7.15-7.18 (m, 2H), 7.08 (dd, J=8.1, 1.5 Hz, 1H), 6.97-7.02 (m, 5H), 3.86 (s, 3H). to reflux for 16 hours partitioned between ethyl acetate and water The organic layer was washed with brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-chlorobenzoic acid (2.35 g, 10 mmol), 1,2-benzenediamine (1.08 g, 10 mmol) and copper (0.63 g, 10 mmol) in chlorobenzene (150 mL) was heated to reflux for 48 hours and filtered. The filter cake was washed with ethyl acetate several times. The combined filtrates were concentrated under vacuum and the residue was purified by flash column chromatography on silica gel with 8:2 hexanes/ethyl acetate to provide 1.20 g (22%) of the desired product. MS (DCI) m/e 289 (M+H)+, 307 (M+NH4)+; 1H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.02 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.24 (d, J=1.8 Hz, 1H), 7.06 (dd, J=8.4, 1.8 Hz, 1H), 6.92-6.95 (m, 5H). was heated to reflux for 48 hours filtered The filter cake was washed with ethyl acetate several times The combined filtrates were concentrated under vacuum the residue was purified by flash column chromatography on silica gel with 8:2 hexanes/ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of Example 9 (116 mg, 0.4 mmol), 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (150 mg, 0.6 mmol), Pd(PPh3)4 (23 mg, 0.02 mmol), and CsF (121 mg, 0.8 mmol) in DME (20 mL) and methanol (10 mL) was heated to reflux for 16 hours, cooled to room temperature, and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 0.108 g (81%) of the desired product. MS (DCI) m/e 333 (M+H)+, 350 (M+NH4)+; 1H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.02 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.24 (d, J=1.8 Hz, 1H), 7.15-7.18 (m, 2H), 7.08 (dd, J=8.1, 1.5 Hz, 1H), 6.97-7.02 (m, 5H), 3.86 (s, 3H). to reflux for 16 hours partitioned between ethyl acetate and water The organic layer was washed with brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-chlorobenzoic acid (2.35 g, 10 mmol), 1,2-benzenediamine (1.08 g, 10 mmol) and copper (0.63 g, 10 mmol) in chlorobenzene (150 mL) was heated to reflux for 48 hours and filtered. The filter cake was washed with ethyl acetate several times. The combined filtrates were concentrated under vacuum and the residue was purified by flash column chromatography on silica gel with 8:2 hexanes/ethyl acetate to provide 1.20 g (22%) of the desired product. MS (DCI) m/e 289 (M+H)+, 307 (M+NH4)+; 1H NMR (500 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.02 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.24 (d, J=1.8 Hz, 1H), 7.06 (dd, J=8.4, 1.8 Hz, 1H), 6.92-6.95 (m, 5H). was heated to reflux for 48 hours filtered The filter cake was washed with ethyl acetate several times The combined filtrates were concentrated under vacuum the residue was purified by flash column chromatography on silica gel with 8:2 hexanes/ethyl acetate