1-(3-bromophenyl)ethanol

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a stirred and ice-cooled mixture of 1.09 g (27.4 mmol) NaH (60% in mineral oil) in 20 mL dry DMF was added a solution of 5.00 g (24.9 mmol) 1-(3-bromo-phenyl)-ethanol in 10 mL dry DMF under argon atmosphere. The mixture was stirred for 30 min at 0° C. 1.70 mL (27.4 mmol) methyl iodide was added and stirring was continued for 4 h at RT. The mixture was worked up by adding water, followed by extraction with EtOAc. The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (Cyc/EtOAc=9/1). ice-cooled The mixture was stirred for 30 min at 0° C stirring followed by extraction with EtOAc The combined organic phases were dried over sodium sulfate filtered concentrated in vacuo The crude material was purified by flash chromatography (Cyc/EtOAc=9/1)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 3-bromobenzaldehyde (5.0 g, 27 mmol) was dissolved in anhydrous dichloromethane (200 mL) under a dry nitrogen atmosphere and cooled in a dry ice/acetone bath to −78° C. Trimethyl aluminum 2M solution in toluene (16.2 mL, 32 mmol) was added dropwise. After 0.5 h the reaction mixture was allowed to warm to room temperature during which time the cloudiness of the reaction resolved to a clear yellow solution which then proceeded to a colorless solution. After stirring for 1 h at room temperature the reaction mixture was cooled in an ice bath and 1N HCl (100 mL) was added dropwise. The reaction mixture was transferred to a separatory funnel and the organic layer was isolated, dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography eluting with 1:1 Ethyl acetate/hexane to provide 5.4 g (99%) of A4.1a as a colorless oil. LCMS (M+H−OH)+=183, 185 to warm to room temperature during which time the cloudiness of the reaction was cooled in an ice bath The reaction mixture was transferred to a separatory funnel the organic layer was isolated dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure The crude product was purified by silica gel flash column chromatography eluting with 1:1 Ethyl acetate/hexane to provide 5.4 g (99%) of A4.1a as a colorless oil

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available 3-bromobenzaldehyde (5.0 g, 27 mmol) was dissolved in anhydrous dichloromethane (200 mL) under a dry nitrogen atmosphere and cooled in a dry ice/acetone bath to −78° C. Trimethyl aluminum 2M solution in toluene (16.2 mL, 32 mmol) was added dropwise. After 0.5 h the reaction mixture was allowed to warm to room temperature during which time the cloudiness of the reaction resolved to a clear yellow solution which then proceeded to a colorless solution. After stirring for 1 h at room temperature the reaction mixture was cooled in an ice bath and 1N HCl (100 mL) was added dropwise. The reaction mixture was transferred to a separatory funnel and the organic layer was isolated, dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The crude product was purified by silica gel flash column chromatography eluting with 1:1 Ethyl acetate/hexane to provide 5.4 g (99%) of A4.1a as a colorless oil. LCMS (M+H−OH)+=183, 185 to warm to room temperature during which time the cloudiness of the reaction was cooled in an ice bath The reaction mixture was transferred to a separatory funnel the organic layer was isolated dried over anhydrous magnesium sulfate filtered evaporated under reduced pressure The crude product was purified by silica gel flash column chromatography eluting with 1:1 Ethyl acetate/hexane to provide 5.4 g (99%) of A4.1a as a colorless oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 20 parts of m-bromo-α-methylbenzylalcohol and 16.8 parts of 3,4-dihydropyran is cooled in an ice-bath and there are added 2 drops of hydrochloric acid solution. The whole is stirred overnight at 0° C and then allowed to come to room temperature. The mixture is poured onto ether and shaken successively with a sodium hydrogen carbonate solution and twice with water. The organic layer is separated, dried, filtered and evaporated. The residue is distilled, yielding 2-(m-bromo-α-methylbenzyloxy)tetrahydropyran; bp. 168°-169° C at 12 mm. pressure. is cooled in an ice-bath to come to room temperature The mixture is poured onto ether The organic layer is separated dried filtered evaporated The residue is distilled

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 20 parts of m-bromo-α-methylbenzylalcohol and 16.8 parts of 3,4-dihydropyran is cooled in an ice-bath and there are added 2 drops of hydrochloric acid solution. The whole is stirred overnight at 0° C and then allowed to come to room temperature. The mixture is poured onto ether and shaken successively with a sodium hydrogen carbonate solution and twice with water. The organic layer is separated, dried, filtered and evaporated. The residue is distilled, yielding 2-(m-bromo-α-methylbenzyloxy)tetrahydropyran; bp. 168°-169° C at 12 mm. pressure. is cooled in an ice-bath to come to room temperature The mixture is poured onto ether The organic layer is separated dried filtered evaporated The residue is distilled

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

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (74 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (125 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (61 mg, yield 44%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (88 mg) was added to toluene/triethylamine=1.0/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (138 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 55%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (88 mg) was added to toluene/triethylamine=1.0/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (138 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (88 mg, yield 55%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (83 mg, yield 67%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (72 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (111 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 584%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column