2-chloropropanenitrile

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:

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

Procedure: A mixture of 5-chlorosalicylaldehyde (78 g., 0.5 mole), finely powdered anhydrous potassium carbonate (103.5 g., 0.75 mole) and acetone (500 ml.) is stirred under reflux and 2-chloropropionitrile (33.6 g., 0.375 mole) is added over a period of about 5 minutes. The mixture is heated under reflux for 1.5 hours and then treated with potassium carbonate (34.5 g., 0.25 mole) followed by more 2-chloropropionitrile (11.2 g., 0.125 mole). Heating and stirring are continued for 31/2 hours, after which the reaction mixture is filtered and the filter-cake washed with acetone. Evaporation of the combined filtrate gives 3-chloro-6-(1-cyanoethoxy)-benzaldehyde which is recrystallized from aqueous methanol. under reflux The mixture is heated under reflux for 1.5 hours Heating stirring 2 hours after which the reaction mixture is filtered the filter-cake washed with acetone Evaporation of the combined filtrate

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

Procedure: A mixture of 5-chlorosalicylaldehyde (78 g., 0.5 mole), finely powdered anhydrous potassium carbonate (103.5 g., 0.75 mole) and acetone (500 ml.) is stirred under reflux and 2-chloropropionitrile (33.6 g., 0.375 mole) is added over a period of about 5 minutes. The mixture is heated under reflux for 1.5 hours and then treated with potassium carbonate (34.5 g., 0.25 mole) followed by more 2-chloropropionitrile (11.2 g., 0.125 mole). Heating and stirring are continued for 31/2 hours, after which the reaction mixture is filtered and the filter-cake washed with acetone. Evaporation of the combined filtrate gives 3-chloro-6-(1-cyanoethoxy)-benzaldehyde which is recrystallized from aqueous methanol. under reflux The mixture is heated under reflux for 1.5 hours Heating stirring 2 hours after which the reaction mixture is filtered the filter-cake washed with acetone Evaporation of the combined filtrate

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

Procedure: To a solution of dimethylamine (2M solution in tetrahydrofuran, 4.0 mL, 8.0 mmol) was added 2-(1-chloroethyl)-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-ol (synthesized according to the method of reagent preparation 18 using 2-chloropropionitrile in step 1) (50 mg, 0.21 mmol) and the reaction mixture was stirred in a sealed tube for 16 hours at 80° C. After cooling to room temperature the reaction mixture was concentrated and the residue was partitioned between brine (50 mL) and ethyl acetate (50 mL). The organic layer was separated and washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated to give 2-[1-(dimethylamino)ethyl]-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-ol (50 mg, 96%). MS (EI) for C14H23N3O: 250 (MH+). synthesized After cooling to room temperature the reaction mixture was concentrated the residue was partitioned between brine (50 mL) and ethyl acetate (50 mL) The organic layer was separated washed with brine (20 mL) dried over sodium sulfate filtered concentrated

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

Procedure: To a solution of dimethylamine (2M solution in tetrahydrofuran, 4.0 mL, 8.0 mmol) was added 2-(1-chloroethyl)-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-ol (synthesized according to the method of reagent preparation 18 using 2-chloropropionitrile in step 1) (50 mg, 0.21 mmol) and the reaction mixture was stirred in a sealed tube for 16 hours at 80° C. After cooling to room temperature the reaction mixture was concentrated and the residue was partitioned between brine (50 mL) and ethyl acetate (50 mL). The organic layer was separated and washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated to give 2-[1-(dimethylamino)ethyl]-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-ol (50 mg, 96%). MS (EI) for C14H23N3O: 250 (MH+). synthesized After cooling to room temperature the reaction mixture was concentrated the residue was partitioned between brine (50 mL) and ethyl acetate (50 mL) The organic layer was separated washed with brine (20 mL) dried over sodium sulfate filtered concentrated

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To NaH (0.246 g, 10.2 mmol) in 10 ml of DMF at 20° is added 4-(3-methyl-2-butenoxy)phenol (1.33 g, 10.2 mmol) in 5 ml of DMF. After anion formation is complete, the reaction is cooled to 5° C. and 2-chloropropionitrile (1.095 g, 12.2 mmol) is added gradually. Then, the reaction mixture is warmed to RT and heated at 45° for 18 hrs. The reaction is cooled to RT, poured into ice water and extracted with ether. The combined organic layers are washed with 10% NaOH, followed with water until neutral, and with brine, and dried over calcium sulfate. Ether is removed under vacuum to give 2-[4-(3-methyl-2-butenoxy)phenoxy]propionitrile. Then, the reaction mixture is warmed to RT heated at 45° for 18 hrs The reaction is cooled to RT extracted with ether The combined organic layers are washed with 10% NaOH dried over calcium sulfate Ether is removed under vacuum

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To NaH (0.246 g, 10.2 mmol) in 10 ml of DMF at 20° is added 4-(3-methyl-2-butenoxy)phenol (1.33 g, 10.2 mmol) in 5 ml of DMF. After anion formation is complete, the reaction is cooled to 5° C. and 2-chloropropionitrile (1.095 g, 12.2 mmol) is added gradually. Then, the reaction mixture is warmed to RT and heated at 45° for 18 hrs. The reaction is cooled to RT, poured into ice water and extracted with ether. The combined organic layers are washed with 10% NaOH, followed with water until neutral, and with brine, and dried over calcium sulfate. Ether is removed under vacuum to give 2-[4-(3-methyl-2-butenoxy)phenoxy]propionitrile. Then, the reaction mixture is warmed to RT heated at 45° for 18 hrs The reaction is cooled to RT extracted with ether The combined organic layers are washed with 10% NaOH dried over calcium sulfate Ether is removed under vacuum