1-chloro-2-isothiocyanatobenzene

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:

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

Procedure: To a solution of 1.85 g of potassium t-butoxide in 32.3 ml of a dry tetrahydrofuran was added 2.83 g of methyl 2-cyanomethylbenzoate with stirring under an ice-cooling in a stream of nitrogen, and then to the mixture was added 3.02 g of 2-chlorophenyl isothiocyanate for 10 minutes. The mixture was stirred under an ice-cooling for 10 minutes. To the reaction mixture was added 2.72 g of methyl bromoacetate for 10 minutes, and the mixture was stirred for 80 minutes at room temperature. The reaction mixture was cooled under an ice-bath, and 363 mg of potassium t-butoxide was added to the cold mixture. The mixture was stirred for 1 hour under an ice-cooling. To the reaction mixture was added 70 ml of water for 2 minutes, and the mixture was stirred for 15 minutes. Precipitates were collected by a filtration, and successively washed with water, methanol and hexane, and dried under reduced pressure to obtain 4.87 g of the desired product as white colorless crystals. cooling in a stream of nitrogen The mixture was stirred under an ice- cooling for 10 minutes the mixture was stirred for 80 minutes at room temperature The reaction mixture was cooled under an ice-bath The mixture was stirred for 1 hour under an ice- cooling the mixture was stirred for 15 minutes Precipitates were collected by a filtration successively washed with water, methanol and hexane dried under reduced pressure

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

Procedure: A mixture of 1-chloro-2-isothiocyanatobenzene 1 (0.4 g, 2.33 mmol) and 2-chloropyridine-4-carbohydrazide 11 (0.4 g, 2.33 mmol) in DMF was stirred at ambient temperature for 18 hours, concentrated to dryness, and 20 mL of 10% K2CO3 (aq.) was added. The resulting mixture was stirred under reflux for 6 hours. The clear solution was cooled to ambient temperature, washed with ether, and acidified with 1N HCl. The solid was collected, washed with H2O and ether, and dried to afford compound 13 (4.3 g). Yield: 86%. concentrated to dryness, and 20 mL of 10% K2CO3 (aq.) was added The resulting mixture was stirred under reflux for 6 hours The clear solution was cooled to ambient temperature washed with ether The solid was collected washed with H2O and ether dried

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

Procedure: A mixture of 1-chloro-2-isothiocyanatobenzene 1 (3 g, 17.68 mmol) and isonicotinohydrazide 2 (2.43 g, 17.68 mmol) in acetonitrile was stirred at ambient temperature for 18 hours, concentrated to dryness, and 100 mL of 10% K2CO3 (aq.) was added. The resulting mixture was stirred under reflux for 6 hours. The clear solution was cooled to ambient temperature, washed with ether and acidified with 1N HCl. The solid was collected, washed with H2O and ether, and dried to afford compound 4 (4.3 g). Yield: 86%. concentrated to dryness, and 100 mL of 10% K2CO3 (aq.) was added The resulting mixture was stirred under reflux for 6 hours The clear solution was cooled to ambient temperature washed with ether The solid was collected washed with H2O and ether dried

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

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

Procedure: The compound was prepared substantially in accordance with the procedure detailed in Example 1, using 2,2-diphenylethylamine (1.61 g, 8.1 mmol) and 2-chlorophenyl isothiocyanate (1.1 ml, 8.2 mmol) in 30 ml of DMF. The crude material was purified by recrystallization (hexanes/EtOAc). The compound was prepared substantially in accordance with the procedure The crude material was purified by recrystallization (hexanes/EtOAc)

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

Procedure: By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (190 mg, 0.60 mmol) obtained in Example 1, (3), and 2-chlorophenyl isothiocyanate (196 μL, 1.50 mmol), the title compound (127 mg, yield 44%) was obtained in the same manner as that of Example 20.

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

Procedure: By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (190 mg, 0.60 mmol) obtained in Example 1, (3), and 2-chlorophenyl isothiocyanate (196 μL, 1.50 mmol), the title compound (127 mg, yield 44%) was obtained in the same manner as that of Example 20.