1-chloro-N,N-dimethylpropan-2-amine;hydrochloride

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

Procedure: In a similar fashion, 3-(2-pyridyl)-5-(3-cyano-5-hydroxyphenyl) -1,2,4-oxadiazole (31 mg, 0.12 mmol), potassium carbonate (381mg, 2.8 mmol) and 2-dimethylaminopropyl chloride hydrochloride (51 mg, 0.32 mmol) in N,N-dimethylformamide (1 mL) were heated in a sealed vial at 150° C. for 5 minutes. Standard work up and chromatography afforded 10 mg (24%) of 3-(2-pyridyl)-5-(3-cyano-5-(dimethylaminopropoxy)phenyl) -1,2,4-oxadiazole: 1H NMR (CDCl3): δ-8.86 (d, 1H), 8.23 (d, 1H), 8.14 (s, 1H), 8.03 (s, 1H), 7.91 (t, 1H), 7.49 (m, 1H), 7.41 (s, 1H), 4.17 (t, 2H), 2.49 (t, 2H), 2.28 (s, 6H), 2.02 (q, 2H).

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

Procedure: In a similar fashion, 3-(2-pyridyl)-5-(3-cyano-5-hydroxyphenyl) -1,2,4-oxadiazole (31 mg, 0.12 mmol), potassium carbonate (381mg, 2.8 mmol) and 2-dimethylaminopropyl chloride hydrochloride (51 mg, 0.32 mmol) in N,N-dimethylformamide (1 mL) were heated in a sealed vial at 150° C. for 5 minutes. Standard work up and chromatography afforded 10 mg (24%) of 3-(2-pyridyl)-5-(3-cyano-5-(dimethylaminopropoxy)phenyl) -1,2,4-oxadiazole: 1H NMR (CDCl3): δ-8.86 (d, 1H), 8.23 (d, 1H), 8.14 (s, 1H), 8.03 (s, 1H), 7.91 (t, 1H), 7.49 (m, 1H), 7.41 (s, 1H), 4.17 (t, 2H), 2.49 (t, 2H), 2.28 (s, 6H), 2.02 (q, 2H).

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

Procedure: Sodium hydride (4.28 g; 0.18 mole) is added portionwise with cooling (5°-10° C.) under nitrogen to a solution of 11-cyano-6,11-dihydrodibenz[b,e]oxepin (16.0 g; 0.72 mole), of Example 1A, in dry DMF (320 ml) and stirred at ambient temperature for 11/2 hours. At this time, 2-dimethylaminopropyl chloride hydrochloride (15.92 g; 0.10 mole) is added portionwise while maintaining the temperature below 10° C. Upon completion of the addition, stirring is continued at 80° C. for 20 hours. The reaction mixture is cooled, poured into 2 liters of ice water and extracted with ether. The ether is back extracted with 2 N HCl and the acidic washes combined and made basic with potassium carbonate. After extraction with ether and drying (K2CO3) the ether is removed in vacuo to give a solid. Trituration with hexane and drying provides 7.0 g (32%) of a solid (m.p. 112°-114° C.) of 11-cyano-11-[3-(dimethylamino)propyl]-6,11-dihydrodibenz[b,e]oxepin. while maintaining the temperature below 10° C Upon completion of the addition The reaction mixture is cooled extracted with ether The ether is back extracted with 2 N HCl After extraction with ether drying (K2CO3) the ether is removed in vacuo to give a solid Trituration with hexane and drying

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

Procedure: 46.1 g. of biphenyl in 400 ml. of absolute ether are added at about -33° C. while stirring to 600 ml. of dry, condensed ammonia. 4.2 g. of lithium wire (about 2 cm long pieces, de-greased with cyclohexane) are then added at about -50° C. within 15 minutes. The mixture is held at boiling temperature for 2 hours. It is then cooled to about -70° C. and 15.8 g. of racemic 2-chloro-N,N,1-trimethylethylamine hydrochloride are added portionwise over a period of 10 minutes. The mixture is again warmed to boiling temperature (about -33° C.) and stirred at this temperature for 2 hours. 32 g. of ammonium chloride are then added and the ammonia is distilled off. Subsequently, the mixture is worked-up aqueous: the ether solution is washed with water. The aqueous phase is adjusted to a pH greater than 12 with sodium hydroxide solution and extracted further twice with ether. The ether phases are combined and extracted twice with 2 N aqueous hydrochloric acid. The acid extracts are again made alkaline and extracted with ether. The ether phases are dried, filtered and concentrated. There is obtained an oily product which, after chromatography on a 20-fold amount of silica gel using methylene chloride/methanol (10:1) as the solvent, yields α,N,N-trimethyl-1-phenyl-2,5-cyclohexadien-1-ethylamine. This product is dissolved in ether and converted with hydrogen chloride into the hydrochloride which is recrystallized from methylene chloride/ether. The product has a melting point of 158°-159° C. of dry condensed ammonia for 2 hours The mixture is again warmed temperature (about -33° C.) stirred at this temperature for 2 hours the ammonia is distilled off the ether solution is washed with water extracted further twice with ether extracted twice with 2 N aqueous hydrochloric acid extracted with ether The ether phases are dried filtered concentrated There is obtained an oily product which

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

Procedure: 46.1 g. of biphenyl in 400 ml. of absolute ether are added at about -33° C. while stirring to 600 ml. of dry, condensed ammonia. 4.2 g. of lithium wire (about 2 cm long pieces, de-greased with cyclohexane) are then added at about -50° C. within 15 minutes. The mixture is held at boiling temperature for 2 hours. It is then cooled to about -70° C. and 15.8 g. of racemic 2-chloro-N,N,1-trimethylethylamine hydrochloride are added portionwise over a period of 10 minutes. The mixture is again warmed to boiling temperature (about -33° C.) and stirred at this temperature for 2 hours. 32 g. of ammonium chloride are then added and the ammonia is distilled off. Subsequently, the mixture is worked-up aqueous: the ether solution is washed with water. The aqueous phase is adjusted to a pH greater than 12 with sodium hydroxide solution and extracted further twice with ether. The ether phases are combined and extracted twice with 2 N aqueous hydrochloric acid. The acid extracts are again made alkaline and extracted with ether. The ether phases are dried, filtered and concentrated. There is obtained an oily product which, after chromatography on a 20-fold amount of silica gel using methylene chloride/methanol (10:1) as the solvent, yields α,N,N-trimethyl-1-phenyl-2,5-cyclohexadien-1-ethylamine. This product is dissolved in ether and converted with hydrogen chloride into the hydrochloride which is recrystallized from methylene chloride/ether. The product has a melting point of 158°-159° C. of dry condensed ammonia for 2 hours The mixture is again warmed temperature (about -33° C.) stirred at this temperature for 2 hours the ammonia is distilled off the ether solution is washed with water extracted further twice with ether extracted twice with 2 N aqueous hydrochloric acid extracted with ether The ether phases are dried filtered concentrated There is obtained an oily product which

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

Procedure: In a similar fashion, 3-(2-pyridyl)-5-(3-cyano-5-hydroxyphenyl)-1,2,4-oxadiazole (31 mg, 0.12 mmol), potassium carbonate (381 mg, 2.8 mmol) and 2-dimethylaminopropyl chloride hydrochloride (51 mg, 0.32 mmol) in N,N-dimethylformamide (1 mL) were heated in a sealed vial at 150° C. for 5 minutes. Standard work up and chromatography afforded 10 mg (24%) of 3-(2-pyridyl)-5-(3-cyano-5-(dimethylaminopropoxy)phenyl)-1,2,4-oxadiazole: 1H NMR (CDCl3): δ −8.86 (d, 1H), 8.23 (d, 1H), 8.14 (s, 1H), 8.03 (s, 1H), 7.91 (t, 1H), 7.49 (m, 1H), 7.41 (s, 1H), 4.17 (t, 2H), 2.49 (t, 2H), 2.28 (s, 6H), 2.02 (q, 2H).

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

Procedure: In a similar fashion, 3-(2-pyridyl)-5-(3-cyano-5-hydroxyphenyl) -1,2,4-oxadiazole (31 mg, 0.12 mmol), potassium carbonate (381mg, 2.8 mmol) and 2-dimethylaminopropyl chloride hydrochloride (51 mg, 0.32 mmol) in N,N-dimethylformamide (1 mL) were heated in a sealed vial at 150° C. for 5 minutes. Standard work up and chromatography afforded 10 mg (24%) of 3-(2-pyridyl)-5-(3-cyano-5-(dimethylaminopropoxy)phenyl) -1,2,4-oxadiazole: 1H NMR (CDCl3): δ-8.86 (d, 1H), 8.23 (d, 1H), 8.14 (s, 1H), 8.03 (s, 1H), 7.91 (t, 1H), 7.49 (m, 1H), 7.41 (s, 1H), 4.17 (t, 2H), 2.49 (t, 2H), 2.28 (s, 6H), 2.02 (q, 2H).