4-isothiocyanato-N,N-dimethylnaphthalen-1-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 3-amino-7-chloro-5-phenyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (INTERMEDIATE 1) (0.299 g, 1 mmol) in dichloroethane (15 mi) was added 4-isothiocyanato-N,N-dimethyl-1-naphthalenamine (0.230 g, 1 mmol). The reaction mixture was stirred at room temperature for 17 hours. The solvent was evaporated in vacuo, the residue was triturated with ether and the title compound was obtained as a colorless solid (0.345 g, 65%). 1H-NMR (CD3OD): δ 8.25 (d, 8.4 Hz, 2H), 8.00 (d, J=8.4 Hz, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.85-7.81 (m, 2H), 7.77-7.72 (m, 2H), 7.65 (d, J=8.8 Hz, 1H), 7.61-7.58 (m, 4H), 7.51-7.47 (m, 2H), 7.29 (d, J=2.4 Hz, 1H), 6.01 (s, 1H) and 3.49 (s, 9H). MS (ESI) (M+H)+=528. The solvent was evaporated in vacuo the residue was triturated with ether

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-amino-7-chloro-1,3-dihydro-5-phenyl-1-(2-propenyl)-2H-1,4-benzodiazepin-2-one (INTERMEDIATE 6) (0.162 g, 0.5 mmol) in dichloroethane (5 ml) was added 4-isothiocyanato-N,N-dimethyl-1-naphthalenamine (0.115 g, 0.5 mmol). The reaction mixture was stirred at 70° C. for 4 hours; The solvent was evaporated in vacuo, the residue was triturated with ether and the title compound was obtained as a colorless, solid (0.152 g, 55%). 1H-NMR (CDCl3): δ 8.29-8.27 (m, 1H), 8.08-8.06 (m, 1H), 7.90 (s, 1H), 7.60-7.36 (m, 10H), 7.32 (d, J=2.4 Hz, 1H), 7.09 (d, J=8 Hz, 1H), 6.14 (d, J=7.6 Hz, 1H), 5.76-5.69 (m, 1H), 5.15 (s, 1H), 5.12 (dd, J=1.2 and 7.0 Hz, 1H), 4.57-4.39 (m, 2H) and 2.93 (s, 6H). MS (ESI) (M+H)+=554. The solvent was evaporated in vacuo the residue was triturated with ether

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-amino-7-chloro-1,3-dihydro-5-phenyl-1-(2-propenyl)-2H-1,4-benzodiazepin-2-one (INTERMEDIATE 6) (0.162 g, 0.5 mmol) in dichloroethane (5 ml) was added 4-isothiocyanato-N,N-dimethyl-1-naphthalenamine (0.115 g, 0.5 mmol). The reaction mixture was stirred at 70° C. for 4 hours; The solvent was evaporated in vacuo, the residue was triturated with ether and the title compound was obtained as a colorless, solid (0.152 g, 55%). 1H-NMR (CDCl3): δ 8.29-8.27 (m, 1H), 8.08-8.06 (m, 1H), 7.90 (s, 1H), 7.60-7.36 (m, 10H), 7.32 (d, J=2.4 Hz, 1H), 7.09 (d, J=8 Hz, 1H), 6.14 (d, J=7.6 Hz, 1H), 5.76-5.69 (m, 1H), 5.15 (s, 1H), 5.12 (dd, J=1.2 and 7.0 Hz, 1H), 4.57-4.39 (m, 2H) and 2.93 (s, 6H). MS (ESI) (M+H)+=554. The solvent was evaporated in vacuo the residue was triturated with ether

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-amino-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (INTERMEDIATE 8) (0.03 g, 1 mmol) in dichloroethane (5 ml) was added 4-isothiocyanato-N,N-dimethyl-1-naphthalenamine (0.025 g, 1 mmol). The reaction mixture was stirred at 70° C. for 4 hours. The solvent was evaporated in vacuo, the residue was triturated with ether and the title compound was obtained as a colorless solid (35 mg, 60%). 1H-NMR (CDCl3): δ 8.26 (d, J=8.4 Hz, 1H), 8.03 (d, J=7.6 Hz, 1H), 7.93 (br s, 1H), 7.73-7.06 (m, 11H) 6.10 (d, J=7.6 Hz, 1H), 3.40 (s, 3H) and 2.92 (s, 6H). MS (ESI) (M+H)+=562. The solvent was evaporated in vacuo the residue was triturated with ether

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-amino-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (INTERMEDIATE 8) (0.03 g, 1 mmol) in dichloroethane (5 ml) was added 4-isothiocyanato-N,N-dimethyl-1-naphthalenamine (0.025 g, 1 mmol). The reaction mixture was stirred at 70° C. for 4 hours. The solvent was evaporated in vacuo, the residue was triturated with ether and the title compound was obtained as a colorless solid (35 mg, 60%). 1H-NMR (CDCl3): δ 8.26 (d, J=8.4 Hz, 1H), 8.03 (d, J=7.6 Hz, 1H), 7.93 (br s, 1H), 7.73-7.06 (m, 11H) 6.10 (d, J=7.6 Hz, 1H), 3.40 (s, 3H) and 2.92 (s, 6H). MS (ESI) (M+H)+=562. The solvent was evaporated in vacuo the residue was triturated with ether

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-amino-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (INTERMEDIATE 8) (0.03 g, 1 mmol) in dichloroethane (5 ml) was added 4-isothiocyanato-N,N-dimethyl-1-naphthalenamine (0.025 g, 1 mmol). The reaction mixture was stirred at 70° C. for 4 hours. The solvent was evaporated in vacuo, the residue was triturated with ether and the title compound was obtained as a colorless solid (35 mg, 60%). 1H-NMR (CDCl3): δ 8.26 (d, J=8.4 Hz, 1H), 8.03 (d, J=7.6 Hz, 1H), 7.93 (br s, 1H), 7.73-7.06 (m, 11H) 6.10 (d, J=7.6 Hz, 1H), 3.40 (s, 3H) and 2.92 (s, 6H). MS (ESI) (M+H)+=562. The solvent was evaporated in vacuo the residue was triturated with ether