2-[4-(chloromethyl)phenyl]benzonitrile

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 6-chloro-3-propylpyrimidine-2,4(1H,3H)-dione (3 g), 4-chloromethyl-2'-cyanobiphenyl (4.76 g) and potassium carbonate (2.64 g) in DMF (50 ml) was stirred at room temperature for 3 hours and then at 60° C. for 2 hours. The reaction mixture was concentrated to dryness in vacuo and then the residue was dissolved in methylene chloride. The insoluble material was removed from the reaction mixture by filtration and the filtrate was concentrated to dryness. The resulting residue was purified by column chromatography on silica gel to give colorless crystals (5.9 g, 98%). at 60° C. for 2 hours The reaction mixture was concentrated to dryness in vacuo the residue was dissolved in methylene chloride The insoluble material was removed from the reaction mixture by filtration the filtrate was concentrated to dryness The resulting residue was purified by column chromatography on silica gel

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

Procedure: To vigorously stirred 2-phenylbenzonitrile (68.1 g) under ice-cooling was added titanium tetrachloride (432 g) dropwise for 30 minutes. The precipitated crystals were pulverized and then chloromethyl-methyl ether (61 g) was added dropwise for 20 minutes with stirring under ice-cooling. After stirring at 60° C. for 2 hours, additional chloromethyl-methyl ether (15.3 g) was added and the mixture was stirred for an additional hour. To the reaction mixture was added ethyl acetate (200 ml) dropwise with stirring under ice-cooling. Then ice was added until hydrogen chloride gas development ceased and iced water (400 ml) was added before stirring for a while. The precipitated crystals were filtered and dried. The filtrate was extracted with ethyl acetate, washed with water, and concentrated to dryness in vacuo. The resulting residue was purified by column chromatography on silica gel to give crystals which were combined with the previously obtained crystal and recrystallized from methanol to yield pale yellow prisms (41.8 g, 48%). cooling After stirring at 60° C. for 2 hours the mixture was stirred for an additional hour with stirring under ice- cooling before stirring for a while The precipitated crystals were filtered dried The filtrate was extracted with ethyl acetate washed with water concentrated to dryness in vacuo The resulting residue was purified by column chromatography on silica gel to give crystals which recrystallized from methanol

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

Procedure: A mixture of 6-chloro-3-propylpyrimidine-2,4(1H,3H)-dione (3 g), 4-chloromethyl-2'-cyanobiphenyl (4.76 g) and potassium carbonate (2.64 g) in DMF (50 ml) was stirred at room temperature for 3 hours and then at 60° C. for 2 hours. The reaction mixture was concentrated to dryness in vacuo and then the residue was dissolved in methylene chloride. The insoluble material was removed from the reaction mixture by filtration and the filtrate was concentrated to dryness. The resulting residue was purified by column chromatography on silica gel to give colorless crystals (5.9 g, 98%). at 60° C. for 2 hours The reaction mixture was concentrated to dryness in vacuo the residue was dissolved in methylene chloride The insoluble material was removed from the reaction mixture by filtration the filtrate was concentrated to dryness The resulting residue was purified by column chromatography on silica gel

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

Procedure: A mixture of 6-chloro-3-propylpyrimidine-2,4(1H,3H)-dione (3 g), 4-chloromethyl-2'-cyanobiphenyl (4.76 g) and potassium carbonate (2.64 g) in DMF (50 ml) was stirred at room temperature for 3 hours and then at 60° C. for 2 hours. The reaction mixture was concentrated to dryness in vacuo and then the residue was dissolved in methylene chloride. The insoluble material was removed from the reaction mixture by filtration and the filtrate was concentrated to dryness. The resulting residue was purified by column chromatography on silica gel to give colorless crystals (5.9 g, 98%). at 60° C. for 2 hours The reaction mixture was concentrated to dryness in vacuo the residue was dissolved in methylene chloride The insoluble material was removed from the reaction mixture by filtration the filtrate was concentrated to dryness The resulting residue was purified by column chromatography on silica gel

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

Procedure: To vigorously stirred 2-phenylbenzonitrile (68.1 g) under ice-cooling was added titanium tetrachloride (432 g) dropwise for 30 minutes. The precipitated crystals were pulverized and then chloromethyl-methyl ether (61 g) was added dropwise for 20 minutes with stirring under ice-cooling. After stirring at 60° C. for 2 hours, additional chloromethyl-methyl ether (15.3 g) was added and the mixture was stirred for an additional hour. To the reaction mixture was added ethyl acetate (200 ml) dropwise with stirring under ice-cooling. Then ice was added until hydrogen chloride gas development ceased and iced water (400 ml) was added before stirring for a while. The precipitated crystals were filtered and dried. The filtrate was extracted with ethyl acetate, washed with water, and concentrated to dryness in vacuo. The resulting residue was purified by column chromatography on silica gel to give crystals which were combined with the previously obtained crystal and recrystallized from methanol to yield pale yellow prisms (41.8 g, 48%). cooling After stirring at 60° C. for 2 hours the mixture was stirred for an additional hour with stirring under ice- cooling before stirring for a while The precipitated crystals were filtered dried The filtrate was extracted with ethyl acetate washed with water concentrated to dryness in vacuo The resulting residue was purified by column chromatography on silica gel to give crystals which recrystallized from methanol

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 methyl 2-butylbenzimidazole-7-carboxylate (1.5 g) in DMF (15 ml) was added sodium hydride (60% oil, 0.13 g) under ice-cooling. The mixture was stirred for 20 minutes and there was added 4-(2-cyanophenyl)benzyl chloride (1.5 g). The resultant mixture was stirred for further 5 hours at room temperature and there was added water, followed by extraction with ethyl acetate. The organic layer was washed with water and dried. The solvent was evaporated to dryness, and the residue was purified by column chromatography on silica gel to give a pale yellow oil (2.3 g, 82%). cooling followed by extraction with ethyl acetate The organic layer was washed with water dried The solvent was evaporated to dryness the residue was purified by column chromatography on silica gel

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

Procedure: A mixture of 6-chloro-3-propylpyrimidine-2,4(1H,3H)-dione (3 g), 4-chloromethyl-2'-cyanobiphenyl (4.76 g) and potassium carbonate (2.64 g) in DMF (50 ml) was stirred at room temperature for 3 hours and then at 60° C. for 2 hours. The reaction mixture was concentrated to dryness in vacuo and then the residue was dissolved in methylene chloride. The insoluble material was removed from the reaction mixture by filtration and the filtrate was concentrated to dryness. The resulting residue was purified by column chromatography on silica gel to give colorless crystals (5.9 g, 98%). at 60° C. for 2 hours The reaction mixture was concentrated to dryness in vacuo the residue was dissolved in methylene chloride The insoluble material was removed from the reaction mixture by filtration the filtrate was concentrated to dryness The resulting residue was purified by column chromatography on silica gel

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

Procedure: To vigorously stirred 2-phenylbenzonitrile (68.1 g) under ice-cooling was added titanium tetrachloride (432 g) dropwise for 30 minutes. The precipitated crystals were pulverized and then chloromethyl-methyl ether (61 g) was added dropwise for 20 minutes with stirring under ice-cooling. After stirring at 60° C. for 2 hours, additional chloromethyl-methyl ether (15.3 g) was added and the mixture was stirred for an additional hour. To the reaction mixture was added ethyl acetate (200 ml) dropwise with stirring under ice-cooling. Then ice was added until hydrogen chloride gas development ceased and iced water (400 ml) was added before stirring for a while. The precipitated crystals were filtered and dried. The filtrate was extracted with ethyl acetate, washed with water, and concentrated to dryness in vacuo. The resulting residue was purified by column chromatography on silica gel to give crystals which were combined with the previously obtained crystal and recrystallized from methanol to yield pale yellow prisms (41.8 g, 48%). cooling After stirring at 60° C. for 2 hours the mixture was stirred for an additional hour with stirring under ice- cooling before stirring for a while The precipitated crystals were filtered dried The filtrate was extracted with ethyl acetate washed with water concentrated to dryness in vacuo The resulting residue was purified by column chromatography on silica gel to give crystals which recrystallized from methanol