4-pentylaniline

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:; See reaction.notes.procedure_details.

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 4-pentylaniline to yield 2-[(4-pentylphenyl)amino]phenylacetic acid.

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 4-pentylaniline to yield 2-[(4-pentylphenyl)amino]phenylacetic acid.

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

Procedure: 28.5 g Chloral hydrate (172 mmole) and 170 g sodium sulphate were dissolved in 600 ml water (solution 1). 27.8 ml 4-n-Pentylaniline (157 mmole) was dissolved with 15 ml concentrated HCl in 475 ml water (solution 2). 29.6 ml 50% Aqueous hydroxylamine was dissolved with 42 ml concentrated HCl in 80 ml water (solution 3). While stirring, solution 1 was heated to 60° C., then solution 2 followed by solution 3 were added dropwise. The temperature was raised until reflux for 15 minutes. The reaction mixture was allowed to cool down to room temperature. The solid residue was filtered off, dissolved in 500 ml ethyl acetate and washed three times with 200 ml water. After evaporation, the residue, mainly containing compound 14, was slowly added to an ice cooled beaker containing 100 ml concentrated sulphuric acid, while stirring. After all compound 14 was added, the reaction mixture was allowed to reach room temperature followed by heating at 80° C. for 15 minutes. 1000 g Ice was added and the formed solid was filtered and redissolved in 300 ml ethyl acetate. This solution was washed three times with 200 ml water and evaporated. The resulting residue was purified by flash chromatography (Acros Silicagel 0.060-0.200 mm) using isooctane/acetone 65:35, affording compound 15 as an orange solid (11.4 g, 40% yield). were added dropwise The temperature was raised until reflux for 15 minutes The solid residue was filtered off dissolved in 500 ml ethyl acetate washed three times with 200 ml water After evaporation the residue, mainly containing compound 14, was slowly added to an ice cooled beaker containing 100 ml concentrated sulphuric acid while stirring After all compound 14 was added to reach room temperature by heating at 80° C. for 15 minutes 1000 g Ice was added the formed solid was filtered redissolved in 300 ml ethyl acetate This solution was washed three times with 200 ml water evaporated The resulting residue was purified by flash chromatography (Acros Silicagel 0.060-0.200 mm)

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

Procedure: 28.5 g Chloral hydrate (172 mmole) and 170 g sodium sulphate were dissolved in 600 ml water (solution 1). 27.8 ml 4-n-Pentylaniline (157 mmole) was dissolved with 15 ml concentrated HCl in 475 ml water (solution 2). 29.6 ml 50% Aqueous hydroxylamine was dissolved with 42 ml concentrated HCl in 80 ml water (solution 3). While stirring, solution 1 was heated to 60° C., then solution 2 followed by solution 3 were added dropwise. The temperature was raised until reflux for 15 minutes. The reaction mixture was allowed to cool down to room temperature. The solid residue was filtered off, dissolved in 500 ml ethyl acetate and washed three times with 200 ml water. After evaporation, the residue, mainly containing compound 14, was slowly added to an ice cooled beaker containing 100 ml concentrated sulphuric acid, while stirring. After all compound 14 was added, the reaction mixture was allowed to reach room temperature followed by heating at 80° C. for 15 minutes. 1000 g Ice was added and the formed solid was filtered and redissolved in 300 ml ethyl acetate. This solution was washed three times with 200 ml water and evaporated. The resulting residue was purified by flash chromatography (Acros Silicagel 0.060-0.200 mm) using isooctane/acetone 65:35, affording compound 15 as an orange solid (11.4 g, 40% yield). were added dropwise The temperature was raised until reflux for 15 minutes The solid residue was filtered off dissolved in 500 ml ethyl acetate washed three times with 200 ml water After evaporation the residue, mainly containing compound 14, was slowly added to an ice cooled beaker containing 100 ml concentrated sulphuric acid while stirring After all compound 14 was added to reach room temperature by heating at 80° C. for 15 minutes 1000 g Ice was added the formed solid was filtered redissolved in 300 ml ethyl acetate This solution was washed three times with 200 ml water evaporated The resulting residue was purified by flash chromatography (Acros Silicagel 0.060-0.200 mm)

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

Procedure: An operation similar to that of Example 520-1 was performed using 2-{[4-(carboxymethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid resin synthesized in Example 461-4 and 4-amylaniline (0.098 g) as starting materials. To the obtained resin were added tetrahydrofuran (2.0 mL) and 1 mol/L borane-tetrahydrofuran complex (2.0 mL), and the mixture was stirred at room temperature overnight. The resin was collected by filtration from the reaction mixture, washed once with tetrahydrofuran, twice with tetrahydrofuran/methanol=1:1 solution, and twice with methanol. Then, a solution (4.0 mL) of tetrahydrofuran-methanol-piperidine (1:1:2) was added to the resin, and the mixture was stirred at room temperature overnight. After completion of the reaction, the resin was collected by filtration, washed four times with tetrahydrofuran and twice with methanol, and vacuum dried to give the title pale-yellow resin (0.30 g). The resin was collected by filtration from the reaction mixture washed once with tetrahydrofuran, twice with tetrahydrofuran/methanol=1:1 solution Then, a solution (4.0 mL) of tetrahydrofuran-methanol-piperidine (1:1:2) was added to the resin the mixture was stirred at room temperature overnight After completion of the reaction the resin was collected by filtration washed four times with tetrahydrofuran twice with methanol, and vacuum dried

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

Procedure: An operation similar to that of Example 520-1 was performed using 2-{[4-(carboxymethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid resin synthesized in Example 461-4 and 4-amylaniline (0.098 g) as starting materials. To the obtained resin were added tetrahydrofuran (2.0 mL) and 1 mol/L borane-tetrahydrofuran complex (2.0 mL), and the mixture was stirred at room temperature overnight. The resin was collected by filtration from the reaction mixture, washed once with tetrahydrofuran, twice with tetrahydrofuran/methanol=1:1 solution, and twice with methanol. Then, a solution (4.0 mL) of tetrahydrofuran-methanol-piperidine (1:1:2) was added to the resin, and the mixture was stirred at room temperature overnight. After completion of the reaction, the resin was collected by filtration, washed four times with tetrahydrofuran and twice with methanol, and vacuum dried to give the title pale-yellow resin (0.30 g). The resin was collected by filtration from the reaction mixture washed once with tetrahydrofuran, twice with tetrahydrofuran/methanol=1:1 solution Then, a solution (4.0 mL) of tetrahydrofuran-methanol-piperidine (1:1:2) was added to the resin the mixture was stirred at room temperature overnight After completion of the reaction the resin was collected by filtration washed four times with tetrahydrofuran twice with methanol, and vacuum dried

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

Procedure: In the manner described in example 3, 2-bromophenylacetic acid is condensed with 4-pentylaniline to yield 2-[(4-pentylphenyl)amino]phenylacetic acid.

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

Procedure: 28.5 g Chloral hydrate (172 mmole) and 170 g sodium sulphate were dissolved in 600 ml water (solution 1). 27.8 ml 4-n-Pentylaniline (157 mmole) was dissolved with 15 ml concentrated HCl in 475 ml water (solution 2). 29.6 ml 50% Aqueous hydroxylamine was dissolved with 42 ml concentrated HCl in 80 ml water (solution 3). While stirring, solution 1 was heated to 60° C., then solution 2 followed by solution 3 were added dropwise. The temperature was raised until reflux for 15 minutes. The reaction mixture was allowed to cool down to room temperature. The solid residue was filtered off, dissolved in 500 ml ethyl acetate and washed three times with 200 ml water. After evaporation, the residue, mainly containing compound 14, was slowly added to an ice cooled beaker containing 100 ml concentrated sulphuric acid, while stirring. After all compound 14 was added, the reaction mixture was allowed to reach room temperature followed by heating at 80° C. for 15 minutes. 1000 g Ice was added and the formed solid was filtered and redissolved in 300 ml ethyl acetate. This solution was washed three times with 200 ml water and evaporated. The resulting residue was purified by flash chromatography (Acros Silicagel 0.060-0.200 mm) using isooctane/acetone 65:35, affording compound 15 as an orange solid (11.4 g, 40% yield). were added dropwise The temperature was raised until reflux for 15 minutes The solid residue was filtered off dissolved in 500 ml ethyl acetate washed three times with 200 ml water After evaporation the residue, mainly containing compound 14, was slowly added to an ice cooled beaker containing 100 ml concentrated sulphuric acid while stirring After all compound 14 was added to reach room temperature by heating at 80° C. for 15 minutes 1000 g Ice was added the formed solid was filtered redissolved in 300 ml ethyl acetate This solution was washed three times with 200 ml water evaporated The resulting residue was purified by flash chromatography (Acros Silicagel 0.060-0.200 mm)

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

Procedure: In a similar manner to Example 63, (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg) and 4-pentylaniline (55.5 mg) were used to obtain (2S,4S)-4-fluoro-1-[[N-[4-[N-(4-pentylphenyl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]pyrrolidine-2-carbonitrile (15.7 mg).