2-bromo-6-chloro-4-fluorobenzaldehyde

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 103e (1.0 g, 4.90 mmol, 1.0 eq.), 2-bromo-6-chloro-4-fluorobenzaldehyde (2.76 g, 9.8 mmol, 2.0 eq.), Pd2(dba)3 (224 mg, 0.24 mmol, 0.050 eq.), Xantphos (283 mg, 0.49 mmol, 0.10 eq.), potassium acetate (1.44 g, 14.7 mmol, 3.0 eq.), and 1,4-dioxane (50 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 80° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol to afford 128a as a yellow solid (992 mg, 50%). MS: [M+H]+ 405.1 A 100-mL round-bottomed flask equipped with a reflux condenser The system was evacuated refilled with N2 After this time the reaction was cooled to room temperature filtered The filtrate was concentrated under reduced pressure the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 103e (1.0 g, 4.90 mmol, 1.0 eq.), 2-bromo-6-chloro-4-fluorobenzaldehyde (2.76 g, 9.8 mmol, 2.0 eq.), Pd2(dba)3 (224 mg, 0.24 mmol, 0.050 eq.), Xantphos (283 mg, 0.49 mmol, 0.10 eq.), potassium acetate (1.44 g, 14.7 mmol, 3.0 eq.), and 1,4-dioxane (50 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 80° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol to afford 128a as a yellow solid (992 mg, 50%). MS: [M+H]+ 405.1 A 100-mL round-bottomed flask equipped with a reflux condenser The system was evacuated refilled with N2 After this time the reaction was cooled to room temperature filtered The filtrate was concentrated under reduced pressure the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 103e (1.0 g, 4.90 mmol, 1.0 eq.), 2-bromo-6-chloro-4-fluorobenzaldehyde (2.76 g, 9.8 mmol, 2.0 eq.), Pd2(dba)3 (224 mg, 0.24 mmol, 0.050 eq.), Xantphos (283 mg, 0.49 mmol, 0.10 eq.), potassium acetate (1.44 g, 14.7 mmol, 3.0 eq.), and 1,4-dioxane (50 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 80° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol to afford 128a as a yellow solid (992 mg, 50%). MS: [M+H]+ 405.1 A 100-mL round-bottomed flask equipped with a reflux condenser The system was evacuated refilled with N2 After this time the reaction was cooled to room temperature filtered The filtrate was concentrated under reduced pressure the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 103e (1.0 g, 4.90 mmol, 1.0 eq.), 2-bromo-6-chloro-4-fluorobenzaldehyde (2.76 g, 9.8 mmol, 2.0 eq.), Pd2(dba)3 (224 mg, 0.24 mmol, 0.050 eq.), Xantphos (283 mg, 0.49 mmol, 0.10 eq.), potassium acetate (1.44 g, 14.7 mmol, 3.0 eq.), and 1,4-dioxane (50 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 80° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol to afford 128a as a yellow solid (992 mg, 50%). MS: [M+H]+ 405.1 A 100-mL round-bottomed flask equipped with a reflux condenser The system was evacuated refilled with N2 After this time the reaction was cooled to room temperature filtered The filtrate was concentrated under reduced pressure the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 103e (1.0 g, 4.90 mmol, 1.0 eq.), 2-bromo-6-chloro-4-fluorobenzaldehyde (2.76 g, 9.8 mmol, 2.0 eq.), Pd2(dba)3 (224 mg, 0.24 mmol, 0.050 eq.), Xantphos (283 mg, 0.49 mmol, 0.10 eq.), potassium acetate (1.44 g, 14.7 mmol, 3.0 eq.), and 1,4-dioxane (50 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 80° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol to afford 128a as a yellow solid (992 mg, 50%). MS: [M+H]+ 405.1 A 100-mL round-bottomed flask equipped with a reflux condenser The system was evacuated refilled with N2 After this time the reaction was cooled to room temperature filtered The filtrate was concentrated under reduced pressure the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 103e (1.0 g, 4.90 mmol, 1.0 eq.), 2-bromo-6-chloro-4-fluorobenzaldehyde (2.76 g, 9.8 mmol, 2.0 eq.), Pd2(dba)3 (224 mg, 0.24 mmol, 0.050 eq.), Xantphos (283 mg, 0.49 mmol, 0.10 eq.), potassium acetate (1.44 g, 14.7 mmol, 3.0 eq.), and 1,4-dioxane (50 mL). The system was evacuated and refilled with N2. The reaction mixture was heated at 80° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol to afford 128a as a yellow solid (992 mg, 50%). MS: [M+H]+ 405.1 A 100-mL round-bottomed flask equipped with a reflux condenser The system was evacuated refilled with N2 After this time the reaction was cooled to room temperature filtered The filtrate was concentrated under reduced pressure the residue was purified on silica-gel column eluting with 80:1 dichloromethane/methanol