1-(2-chloroethyl)-4-methoxybenzene

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:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 5.0 grams (0.032 mole) of ethyl piperidin-4-ylcarboxylate, 5.4 grams (0.032 mole) of 1-(2-chloroethyl)-4-methoxybenzene and 4.4 grams (0.032 mole) of potassium carbonate in 50 mL of dried N,N-dimethylformamide was heated at 70° C. for about 16 hours. After this time the reaction mixture was cooled and partitioned between diethyl ether and water. The organic layer was separated and washed with water and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with diethyl ether/hexane mixtures as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 2.4 grams of ethyl N-[2-(4-methoxyphenyl)ethyl]piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure. After this time the reaction mixture was cooled partitioned between diethyl ether and water The organic layer was separated washed with water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue, which concentrated under reduced pressure

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

Procedure: A stirred mixture of 5.0 grams (0.032 mole) of ethyl piperidin-4-ylcarboxylate, 5.4 grams (0.032 mole) of 1-(2-chloroethyl)-4-methoxybenzene and 4.4 grams (0.032 mole) of potassium carbonate in 50 mL of dried N,N-dimethylformamide was heated at 70° C. for about 16 hours. After this time the reaction mixture was cooled and partitioned between diethyl ether and water. The organic layer was separated and washed with water and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with diethyl ether/hexane mixtures as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 2.4 grams of ethyl N-[2-(4-methoxyphenyl)ethyl]-piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure. After this time the reaction mixture was cooled partitioned between diethyl ether and water The organic layer was separated washed with water The organic layer was dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue, which concentrated under reduced pressure

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 4.7 parts of 1-(2-chloroethyl)-4-methoxybenzene, 14 parts of N-(4-piperidinyl)-1-(4-thiazolylmethyl)-1H-benzimidazol-2-amine dihydrobromide.monohydrate, 15 parts of sodium carbonate, 0.3 parts of sodium iodide and 90 parts of N,N-dimethylacetamide was stirred overnight at 80° C. Water was added and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The oily residue was converted into the hydrobromide salt in ethanol. The salt was filtered off and dried, yielding 9 parts of N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-1-(4-thiazolyl)-methyl)-1H-benzimidazol-2-amine dihydrobromide. dihydrate; mp. 239.2° C. (compound 17). the product was extracted with 4-methyl-2-pentanone The extract was dried filtered evaporated The salt was filtered off dried

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

Procedure: A mixture of 4.7 parts of 1-(2-chloroethyl)-4-methoxybenzene, 14 parts of N-(4-piperidinyl)-1-(4-thiazolylmethyl)-1H-benzimidazol-2-amine dihydrobromide.monohydrate, 15 parts of sodium carbonate, 0.3 parts of sodium iodide and 90 parts of N,N-dimethylacetamide was stirred overnight at 80° C. Water was added and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The oily residue was converted into the hydrobromide salt in ethanol. The salt was filtered off and dried, yielding 9 parts of N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-1-(4-thiazolyl)-methyl)-1H-benzimidazol-2-amine dihydrobromide. dihydrate; mp. 239.2° C. (compound 17). the product was extracted with 4-methyl-2-pentanone The extract was dried filtered evaporated The salt was filtered off dried

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

Procedure: A mixture of 1.9 parts of 1-(2-chloroethyl)-4-methoxybenzene, 5 parts of 7-[(4-fluorophenyl)methyl]-8-(4-piperidinylmethyl)-7H-purin-6-ol dihydrobromide, 4 parts of sodium carbonate and 45 parts of N,N-dimethylacetamide was stirred overnight at 70° C. After cooling, the reaction mixture was filtered over diatomaceous earth and the filtrate was evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetontrile. The product was filtered off and dried, yielding 2.2 parts (46%) of 7-[(4-fluorophenyl)methyl]-8-[[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methyl]-7H-purin-6-ol; mp. 122.2° C. (compound 62). After cooling the reaction mixture was filtered over diatomaceous earth the filtrate was evaporated The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol The pure fractions were collected the eluent was evaporated The residue was crystallized from acetontrile The product was filtered off dried

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

Procedure: A mixture of 1.9 parts of 1-(2-chloroethyl)-4-methoxybenzene, 5 parts of 7-[(4-fluorophenyl)methyl]-8-(4-piperidinylmethyl)-7H-purin-6-ol dihydrobromide, 4 parts of sodium carbonate and 45 parts of N,N-dimethylacetamide was stirred overnight at 70° C. After cooling, the reaction mixture was filtered over diatomaceous earth and the filtrate was evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetontrile. The product was filtered off and dried, yielding 2.2 parts (46%) of 7-[(4-fluorophenyl)methyl]-8-[[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methyl]-7H-purin-6-ol; mp. 122.2° C. (compound 62). After cooling the reaction mixture was filtered over diatomaceous earth the filtrate was evaporated The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol The pure fractions were collected the eluent was evaporated The residue was crystallized from acetontrile The product was filtered off dried

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

Procedure: 2-{(2-Hydroxy-ethyl)-[2-(4-methoxy-phenyl)-ethyl]-amino}-ethanol was prepared according to the general method as outlined in example 83. Starting from diethanolamine (10.0 g, excess). and 1-(2-chloroethyl)4-methoxybenzene (8.5 g, 50 mmol). Yield 1 -1 g, (92%); yellow oil; MS: 240 (M+H)+.