piperazine-1-carbonitrile

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

Procedure: In a flask fitted with stirrer, thermometer, and drying tube is placed 100 ml. of chloroform, 12.0 g. (0.05 mole) of 4-amino-2-bromo-6,7-dimethoxyquinazoline (prepared by the method of U.S. Pat. No. 3,511,836) and 5.8 g. (0.052 mole) of 1-cyanopiperazine. The mixture is maintained at 50° C. for 24 hours after which 2N potassium hydroxide solution is added at room temperature to adjust to pH 9.5. The organic layer is separated and the aqueous phase extracted again with chloroform and the combined extracts are evaporated to dryness to obtain 2-(4-cyanopiperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline. In a flask fitted with stirrer thermometer, and drying tube is added at room temperature The organic layer is separated the aqueous phase extracted again with chloroform the combined extracts are evaporated to dryness

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

Procedure: In a flask fitted with stirrer, thermometer, and drying tube is placed 100 ml. of chloroform, 12.0 g. (0.05 mole) of 4-amino-2-bromo-6,7-dimethoxyquinazoline (prepared by the method of U.S. Pat. No. 3,511,836) and 5.8 g. (0.052 mole) of 1-cyanopiperazine. The mixture is maintained at 50° C. for 24 hours after which 2N potassium hydroxide solution is added at room temperature to adjust to pH 9.5. The organic layer is separated and the aqueous phase extracted again with chloroform and the combined extracts are evaporated to dryness to obtain 2-(4-cyanopiperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline. In a flask fitted with stirrer thermometer, and drying tube is added at room temperature The organic layer is separated the aqueous phase extracted again with chloroform the combined extracts are evaporated to dryness

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

Procedure: A stirred solution of 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (3.48 g, 15.65 mmol), piperazine-1-carbonitrile (2 g, 17.99 mmol) and DIPEA (3.54 mL, 20.34 mmol) in DMF (20 mL) was heated at 70° C. for 1 hour. The solution was evaporated and partitioned between DCM and 1M aqueous K2CO3. The organic phase was washed with brine, dried over MgSO4, evaporated and triturated with ether. The precipitate was collected by filtration, washed with ether and dried under vacuum to afford 4-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazine-1-carbonitrile (4.29 g, 92%) as a cream crystalline solid. The solution was evaporated partitioned between DCM and 1M aqueous K2CO3 The organic phase was washed with brine dried over MgSO4 evaporated triturated with ether The precipitate was collected by filtration washed with ether dried under vacuum

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

Procedure: In a flask fitted with stirrer, thermometer, and drying tube is placed 100 ml. of chloroform, 12.0 g. (0.05 mole) of 4-amino-2-bromo-6,7-dimethoxyquinazoline (prepared by the method of U.S. Pat. No. 3,511,836) and 5.8 g. (0.052 mole) of 1-cyanopiperazine. The mixture is maintained at 50° C. for 24 hours after which 2N potassium hydroxide solution is added at room temperature to adjust to pH 9.5. The organic layer is separated and the aqueous phase extracted again with chloroform and the combined extracts are evaporated to dryness to obtain 2-(4-cyanopiperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline. In a flask fitted with stirrer thermometer, and drying tube is added at room temperature The organic layer is separated the aqueous phase extracted again with chloroform the combined extracts are evaporated to dryness