(2-aminophenyl)-(2-fluorophenyl)methanone

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

実験手順: The procedure of Example 1 was carried out using 2-amino-2'-fluorobenzophenone (1.26 gm, 5.86 mmol), N-Boc-β-(2-thienyl)-DL-alanine (1.75 gm, 6.45 mmol), and DCC (6.45 ml of 1.0M solution in CH2Cl2) in CH2Cl2 (25 ml). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which was deprotected and cyclized by the procedure of Example 2. After stirring 3 days, the mixture was evaporated in vacuo, treated with H2O (50 ml) and extracted with EtOAc (2×100 ml). The combined organic extracts were washed with brine (50 ml), dried over MgSO4, filtered, and evaporated to dryness in vacuo. The resulting foam was crystallized from Et2O to give the title compound as a white solid. The solid was dried in vacuo at 65° C.: (m.p. 189°-91° C.). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which the mixture was evaporated in vacuo treated with H2O (50 ml) extracted with EtOAc (2×100 ml) The combined organic extracts were washed with brine (50 ml) dried over MgSO4 filtered evaporated to dryness in vacuo The resulting foam was crystallized from Et2O

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

実験手順: The procedure of Example 1 was carried out using 2-amino-2'-fluorobenzophenone (1.26 gm, 5.86 mmol), N-Boc-β-(2-thienyl)-DL-alanine (1.75 gm, 6.45 mmol), and DCC (6.45 ml of 1.0M solution in CH2Cl2) in CH2Cl2 (25 ml). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which was deprotected and cyclized by the procedure of Example 2. After stirring 3 days, the mixture was evaporated in vacuo, treated with H2O (50 ml) and extracted with EtOAc (2×100 ml). The combined organic extracts were washed with brine (50 ml), dried over MgSO4, filtered, and evaporated to dryness in vacuo. The resulting foam was crystallized from Et2O to give the title compound as a white solid. The solid was dried in vacuo at 65° C.: (m.p. 189°-91° C.). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which the mixture was evaporated in vacuo treated with H2O (50 ml) extracted with EtOAc (2×100 ml) The combined organic extracts were washed with brine (50 ml) dried over MgSO4 filtered evaporated to dryness in vacuo The resulting foam was crystallized from Et2O

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

実験手順: The procedure of Example 1 was carried out using 2-amino-2'-fluorobenzophenone (1.26 gm, 5.86 mmol), N-Boc-β-(2-thienyl)-DL-alanine (1.75 gm, 6.45 mmol), and DCC (6.45 ml of 1.0M solution in CH2Cl2) in CH2Cl2 (25 ml). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which was deprotected and cyclized by the procedure of Example 2. After stirring 3 days, the mixture was evaporated in vacuo, treated with H2O (50 ml) and extracted with EtOAc (2×100 ml). The combined organic extracts were washed with brine (50 ml), dried over MgSO4, filtered, and evaporated to dryness in vacuo. The resulting foam was crystallized from Et2O to give the title compound as a white solid. The solid was dried in vacuo at 65° C.: (m.p. 189°-91° C.). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which the mixture was evaporated in vacuo treated with H2O (50 ml) extracted with EtOAc (2×100 ml) The combined organic extracts were washed with brine (50 ml) dried over MgSO4 filtered evaporated to dryness in vacuo The resulting foam was crystallized from Et2O

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

実験手順: A solution of 86 g (0.4 mole) of 2-amino-2'-fluorobenzophenone in 3 liters of methylene chloride was cooled to -65° C. and 54 g (0.4 mole) of ethyl methylthioacetate was added. A solution of 46 g (0.42 mole) of 95% tertiary butoxy chloride in 100 ml of methylene chloride was added dropwise, keeping the temperature below -65° C. One hour after addition was complete, 41 g (0.4 mole) of triethylamine was added dropwise and the mixture allowed to warm to room temperature. The solution was concentrated to about 1400 ml and then washed with water. The organic solution was concentrated and the residue dissolved in 800 ml methanol containing 60 ml of concentrated hydrochloric acid. The mixture was heated at reflux for one hour followed by cooling. The mixture stood overnight, then the crystals were collected and recrystallized from 20% aqueous ethanol to give 66 g (55%)pale yellow needles; m.p. 147.0°-148.5° C. the temperature below -65° C One hour after addition The solution was concentrated to about 1400 ml washed with water The organic solution was concentrated the residue dissolved in 800 ml methanol containing 60 ml of concentrated hydrochloric acid The mixture was heated at reflux for one hour by cooling the crystals were collected recrystallized from 20% aqueous ethanol

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

実験手順: The procedure of Example 1 was carried out using 2-amino-2'-fluorobenzophenone (1.26 gm, 5.86 mmol), N-Boc-β-(2-thienyl)-DL-alanine (1.75 gm, 6.45 mmol), and DCC (6.45 ml of 1.0M solution in CH2Cl2) in CH2Cl2 (25 ml). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which was deprotected and cyclized by the procedure of Example 2. After stirring 3 days, the mixture was evaporated in vacuo, treated with H2O (50 ml) and extracted with EtOAc (2×100 ml). The combined organic extracts were washed with brine (50 ml), dried over MgSO4, filtered, and evaporated to dryness in vacuo. The resulting foam was crystallized from Et2O to give the title compound as a white solid. The solid was dried in vacuo at 65° C.: (m.p. 189°-91° C.). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which the mixture was evaporated in vacuo treated with H2O (50 ml) extracted with EtOAc (2×100 ml) The combined organic extracts were washed with brine (50 ml) dried over MgSO4 filtered evaporated to dryness in vacuo The resulting foam was crystallized from Et2O

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

実験手順: The procedure of Example 1 was carried out using 2-amino-2'-fluorobenzophenone (1.26 gm, 5.86 mmol), N-Boc-β-(2-thienyl)-DL-alanine (1.75 gm, 6.45 mmol), and DCC (6.45 ml of 1.0M solution in CH2Cl2) in CH2Cl2 (25 ml). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which was deprotected and cyclized by the procedure of Example 2. After stirring 3 days, the mixture was evaporated in vacuo, treated with H2O (50 ml) and extracted with EtOAc (2×100 ml). The combined organic extracts were washed with brine (50 ml), dried over MgSO4, filtered, and evaporated to dryness in vacuo. The resulting foam was crystallized from Et2O to give the title compound as a white solid. The solid was dried in vacuo at 65° C.: (m.p. 189°-91° C.). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which the mixture was evaporated in vacuo treated with H2O (50 ml) extracted with EtOAc (2×100 ml) The combined organic extracts were washed with brine (50 ml) dried over MgSO4 filtered evaporated to dryness in vacuo The resulting foam was crystallized from Et2O