N-[4-(hydroxymethyl)phenyl]prop-2-enamide

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: p-Aminobenzyl alcohol (12.31 g, 100 mmol) was dissolved in a mixture of dichloromethane (200 mL) and tetrahydrofuran (20 mL) containing N,N-diisopropylethylamine (35 mL, 200 mmol). The resulting homogeneous solution was then cooled to 0° C. and acryloyl chloride (8.2 mL, 100 mmol) was added drop-wise over a 30-minute period while keeping the internal temperature of the reaction mixture below 20° C. The reaction mixture was stirred at 0° C. for about 60 minutes. The reaction mixture was poured into ice-cold 1M hydrochloric acid (0.6 L) and the organic layer was separated and evaporated to dryness to give a crude material (5 g) consisting primarily of the bis-acylated side product. The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) and the combined ethyl acetate layers were dried with sodium sulfate, filtered and concentrated under reduced pressure to provide a residue. Trituration of the residue with ethyl acetate yielded the title compound (10.5 g, 98.5% pure). An additional 2 g of the title compound were obtained by trituration of the crude material obtained from the dichloromethane layer. the internal temperature of the reaction mixture below 20° C the organic layer was separated evaporated to dryness to give a crude material (5 g) The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) the combined ethyl acetate layers were dried with sodium sulfate filtered concentrated under reduced pressure to provide a residue

反応条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-[4-(hydroxymethyl)phenyl]acrylamide (intermediate 79; 0.3 g, 1.7 mmol) in tetrahydrofuran (6 mL) was added trans-4-(methylamino)cyclohexyl hydroxy(di-2-thienyl)acetate (intermediate 5; 0.5 g, 1.42 mmol). The mixture was placed in a sealed vessel and stirred for 4 days at 75° C. The solvent was removed under reduced pressure and the crude obtained was purified by preparative reversed-phase HPLC (System 2) to give the title compound (34%). The mixture was placed in a sealed vessel The solvent was removed under reduced pressure the crude obtained was purified by preparative reversed-phase HPLC (System 2)

反応条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-[4-(hydroxymethyl)phenyl]acrylamide (intermediate 79; 0.3 g, 1.7 mmol) in tetrahydrofuran (6 mL) was added trans-4-(methylamino)cyclohexyl hydroxy(di-2-thienyl)acetate (intermediate 5; 0.5 g, 1.42 mmol). The mixture was placed in a sealed vessel and stirred for 4 days at 75° C. The solvent was removed under reduced pressure and the crude obtained was purified by preparative reversed-phase HPLC (System 2) to give the title compound (34%). The mixture was placed in a sealed vessel The solvent was removed under reduced pressure the crude obtained was purified by preparative reversed-phase HPLC (System 2)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: p-Aminobenzyl alcohol (12.31 g, 100 mmol) was dissolved in a mixture of dichloromethane (200 mL) and tetrahydrofuran (20 mL) containing N,N-diisopropylethylamine (35 mL, 200 mmol). The resulting homogeneous solution was then cooled to 0° C. and acryloyl chloride (8.2 mL, 100 mmol) was added drop-wise over a 30-minute period while keeping the internal temperature of the reaction mixture below 20° C. The reaction mixture was stirred at 0° C. for about 60 minutes. The reaction mixture was poured into ice-cold 1M hydrochloric acid (0.6 L) and the organic layer was separated and evaporated to dryness to give a crude material (5 g) consisting primarily of the bis-acylated side product. The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) and the combined ethyl acetate layers were dried with sodium sulfate, filtered and concentrated under reduced pressure to provide a residue. Trituration of the residue with ethyl acetate yielded the title compound (10.5 g, 98.5% pure). An additional 2 g of the title compound were obtained by trituration of the crude material obtained from the dichloromethane layer. the internal temperature of the reaction mixture below 20° C the organic layer was separated evaporated to dryness to give a crude material (5 g) The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) the combined ethyl acetate layers were dried with sodium sulfate filtered concentrated under reduced pressure to provide a residue

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: p-Aminobenzyl alcohol (12.31 g, 100 mmol) was dissolved in a mixture of dichloromethane (200 mL) and tetrahydrofuran (20 mL) containing N,N-diisopropylethylamine (35 mL, 200 mmol). The resulting homogeneous solution was then cooled to 0° C. and acryloyl chloride (8.2 mL, 100 mmol) was added drop-wise over a 30-minute period while keeping the internal temperature of the reaction mixture below 20° C. The reaction mixture was stirred at 0° C. for about 60 minutes. The reaction mixture was poured into ice-cold 1M hydrochloric acid (0.6 L) and the organic layer was separated and evaporated to dryness to give a crude material (5 g) consisting primarily of the bis-acylated side product. The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) and the combined ethyl acetate layers were dried with sodium sulfate, filtered and concentrated under reduced pressure to provide a residue. Trituration of the residue with ethyl acetate yielded the title compound (10.5 g, 98.5% pure). An additional 2 g of the title compound were obtained by trituration of the crude material obtained from the dichloromethane layer. the internal temperature of the reaction mixture below 20° C the organic layer was separated evaporated to dryness to give a crude material (5 g) The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) the combined ethyl acetate layers were dried with sodium sulfate filtered concentrated under reduced pressure to provide a residue

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: p-Aminobenzyl alcohol (12.31 g, 100 mmol) was dissolved in a mixture of dichloromethane (200 mL) and tetrahydrofuran (20 mL) containing N,N-diisopropylethylamine (35 mL, 200 mmol). The resulting homogeneous solution was then cooled to 0° C. and acryloyl chloride (8.2 mL, 100 mmol) was added drop-wise over a 30-minute period while keeping the internal temperature of the reaction mixture below 20° C. The reaction mixture was stirred at 0° C. for about 60 minutes. The reaction mixture was poured into ice-cold 1M hydrochloric acid (0.6 L) and the organic layer was separated and evaporated to dryness to give a crude material (5 g) consisting primarily of the bis-acylated side product. The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) and the combined ethyl acetate layers were dried with sodium sulfate, filtered and concentrated under reduced pressure to provide a residue. Trituration of the residue with ethyl acetate yielded the title compound (10.5 g, 98.5% pure). An additional 2 g of the title compound were obtained by trituration of the crude material obtained from the dichloromethane layer. the internal temperature of the reaction mixture below 20° C the organic layer was separated evaporated to dryness to give a crude material (5 g) The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) the combined ethyl acetate layers were dried with sodium sulfate filtered concentrated under reduced pressure to provide a residue

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: p-Aminobenzyl alcohol (12.31 g, 100 mmol) was dissolved in a mixture of dichloromethane (200 mL) and tetrahydrofuran (20 mL) containing N,N-diisopropylethylamine (35 mL, 200 mmol). The resulting homogeneous solution was then cooled to 0° C. and acryloyl chloride (8.2 mL, 100 mmol) was added drop-wise over a 30-minute period while keeping the internal temperature of the reaction mixture below 20° C. The reaction mixture was stirred at 0° C. for about 60 minutes. The reaction mixture was poured into ice-cold 1M hydrochloric acid (0.6 L) and the organic layer was separated and evaporated to dryness to give a crude material (5 g) consisting primarily of the bis-acylated side product. The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) and the combined ethyl acetate layers were dried with sodium sulfate, filtered and concentrated under reduced pressure to provide a residue. Trituration of the residue with ethyl acetate yielded the title compound (10.5 g, 98.5% pure). An additional 2 g of the title compound were obtained by trituration of the crude material obtained from the dichloromethane layer. the internal temperature of the reaction mixture below 20° C the organic layer was separated evaporated to dryness to give a crude material (5 g) The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) the combined ethyl acetate layers were dried with sodium sulfate filtered concentrated under reduced pressure to provide a residue

反応条件: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of N-[4-(hydroxymethyl)phenyl]acrylamide (intermediate 79; 0.3 g, 1.7 mmol) in tetrahydrofuran (6 mL) was added trans-4-(methylamino)cyclohexyl hydroxy(di-2-thienyl)acetate (intermediate 5; 0.5 g, 1.42 mmol). The mixture was placed in a sealed vessel and stirred for 4 days at 75° C. The solvent was removed under reduced pressure and the crude obtained was purified by preparative reversed-phase HPLC (System 2) to give the title compound (34%). The mixture was placed in a sealed vessel The solvent was removed under reduced pressure the crude obtained was purified by preparative reversed-phase HPLC (System 2)