614-14-2

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

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (76 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 (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (57 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 (38 mg, yield 29%). 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-[(6,7Dimethoxy-4-quinolyl)oxy]2,5-dimethylaniline (89 mg) was added to toluene/triethylamine=10/1 (9 ml ) and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (126 mg), in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (63 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 (58 mg, yield 39%). 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-[(6,7Dimethoxy-4-quinolyl)oxy]2,5-dimethylaniline (89 mg) was added to toluene/triethylamine=10/1 (9 ml ) and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (126 mg), in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (63 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 (58 mg, yield 39%). 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 (90 mg) was added to toluene/triethylamine=10/1 (9 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 form 15 min. Subsequently, 1-phenyl-1-butanol (62 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 (59 mg, yield 40%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux form 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 (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepared a solution. A solution of triphosgene (118 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (59 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 (78 mg, yield 58%). the mixture was heated under reflux to prepared 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 (78 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepared a solution. A solution of triphosgene (118 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (59 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 (78 mg, yield 58%). the mixture was heated under reflux to prepared 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: To a mixture of 792 mg of 4-hydroxycoumarin and 809 mg of 1-phenyl- 1 -butanol of Preparation 12 in 25 mL of dioxane under an argon atmosphere is added 2.6 mL of boron trifluoride etherate. The resulting yellow solution is left to stir at room temperature overnight. The volatiles are removed under reduced pressure and the residue is partioned between diethyl ether and 1N sodium hydroxide. The basic aqueous phase is washed with diethyl ether, acidified to pH=1 with 6N hydrochloric acid. The resulting precipitant is repeatedly extracted with dichloromethane (methanol-chloroform co-solvents). The combined dichloromethane extracts are washed once with dilute sodium bicarbonate to remove most of the unreacted 4-hydroxycoumarin, then brine, dried (magnesium sulfate), and finally concentrated under reduced pressure. The residue is adsorbed onto silica and flash column chromatographed with 40% to 50% ethyl acetate in hexane to yield 183 mg of the title product as white crystals. The resulting yellow solution is left The volatiles are removed under reduced pressure The basic aqueous phase is washed with diethyl ether The resulting precipitant is repeatedly extracted with dichloromethane (methanol-chloroform co-solvents) The combined dichloromethane extracts are washed once with dilute sodium bicarbonate to remove most of the unreacted 4-hydroxycoumarin brine, dried (magnesium sulfate) finally concentrated under reduced pressure chromatographed with 40% to 50% ethyl acetate in hexane

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

Procedure: To a mixture of 792 mg of 4-hydroxycoumarin and 809 mg of 1-phenyl- 1 -butanol of Preparation 12 in 25 mL of dioxane under an argon atmosphere is added 2.6 mL of boron trifluoride etherate. The resulting yellow solution is left to stir at room temperature overnight. The volatiles are removed under reduced pressure and the residue is partioned between diethyl ether and 1N sodium hydroxide. The basic aqueous phase is washed with diethyl ether, acidified to pH=1 with 6N hydrochloric acid. The resulting precipitant is repeatedly extracted with dichloromethane (methanol-chloroform co-solvents). The combined dichloromethane extracts are washed once with dilute sodium bicarbonate to remove most of the unreacted 4-hydroxycoumarin, then brine, dried (magnesium sulfate), and finally concentrated under reduced pressure. The residue is adsorbed onto silica and flash column chromatographed with 40% to 50% ethyl acetate in hexane to yield 183 mg of the title product as white crystals. The resulting yellow solution is left The volatiles are removed under reduced pressure The basic aqueous phase is washed with diethyl ether The resulting precipitant is repeatedly extracted with dichloromethane (methanol-chloroform co-solvents) The combined dichloromethane extracts are washed once with dilute sodium bicarbonate to remove most of the unreacted 4-hydroxycoumarin brine, dried (magnesium sulfate) finally concentrated under reduced pressure chromatographed with 40% to 50% ethyl acetate in hexane

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

Procedure: To a stirring solution of 890 mg of commercially available butyrophenone in 30 mL of diethyl ether under an argon atmosphere at 0° C. is slowly added 250 mg of lithium aluminum hydride in portions. After 2 hours the grey suspension is slowly treated with 0.25 mL of water followed by 1.10 mL of 1N sodium hydroxide. After 0.5 hours the resulting whim precipitant is filtered through a pad of magnesium sulfate with diethyl ether washings. The filtrate is concentrated under reduced pressure to afford 0.90 g of the title product as a clear, colorless oil. This product may be used directly in the next reaction without further purification. at 0° C. After 0.5 hours the resulting whim precipitant is filtered through a pad of magnesium sulfate with diethyl ether washings The filtrate is concentrated under reduced pressure

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

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (76 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 (115 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (57 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 (38 mg, yield 29%). 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-[(6,7Dimethoxy-4-quinolyl)oxy]2,5-dimethylaniline (89 mg) was added to toluene/triethylamine=10/1 (9 ml ) and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (126 mg), in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 1-phenyl-1-butanol (63 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 (58 mg, yield 39%). 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 (90 mg) was added to toluene/triethylamine=10/1 (9 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 form 15 min. Subsequently, 1-phenyl-1-butanol (62 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 (59 mg, yield 40%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux form 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