4-FLUOROPHTHALONITRILE

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

Procedure: The compound obtained using 2-{[4-(2-aminoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester synthesized in Example 7 and 4-fluorophthalonitrile as starting materials and by operations similar to those of Example 265-1 and Example 265-2 was treated with dichloromethane and trifluoroacetic acid, and the mixture was stirred at room temperature for 12 hr. The reaction solution was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography (elution solvent; 0.05% trifluoroacetic acid-water:0.05% trifluoroacetic acid-acetonitrile) to give the title compound. The compound obtained The reaction solution was concentrated under reduced pressure the residue was purified by high performance liquid chromatography (elution solvent; 0.05% trifluoroacetic acid-water:0.05% trifluoroacetic acid-acetonitrile)

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

Procedure: The compound obtained using 2-{[4-(2-aminoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester synthesized in Example 7 and 4-fluorophthalonitrile as starting materials and by operations similar to those of Example 265-1 and Example 265-2 was treated with dichloromethane and trifluoroacetic acid, and the mixture was stirred at room temperature for 12 hr. The reaction solution was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography (elution solvent; 0.05% trifluoroacetic acid-water:0.05% trifluoroacetic acid-acetonitrile) to give the title compound. The compound obtained The reaction solution was concentrated under reduced pressure the residue was purified by high performance liquid chromatography (elution solvent; 0.05% trifluoroacetic acid-water:0.05% trifluoroacetic acid-acetonitrile)

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

Procedure: To a solution of N-(9-ethyl-9H-carbazol-3-yl)-5-hydroxy-3-methylpentanamine (0.40 g, 1.23 mmol) in DMF (10.0 mL) was added potassium-t-butoxide (0.304 g, 2.71 mmol) under argon atmosphere. The mixture was stirred at room temperature for 15 min, and 4-fluorophthalonitrile (0.270 g, 1.85 mmol) was added thereto. The reaction solution was stirred at room temperature for 14 hr, and ethyl acetate (100 mL) was added thereto. The organic layer was washed with cold water (2×25 mL) and saturated brine (2×25 mL), and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC to give the title compound (0.285 g, 51%) as a white powder. The reaction solution was stirred at room temperature for 14 hr The organic layer was washed with cold water (2×25 mL) and saturated brine (2×25 mL) dried the solvent was evaporated under reduced pressure The obtained residue was purified by preparative HPLC

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

Procedure: To a solution of N-(9-ethyl-9H-carbazol-3-yl)-5-hydroxy-3-methylpentanamine (0.40 g, 1.23 mmol) in DMF (10.0 mL) was added potassium-t-butoxide (0.304 g, 2.71 mmol) under argon atmosphere. The mixture was stirred at room temperature for 15 min, and 4-fluorophthalonitrile (0.270 g, 1.85 mmol) was added thereto. The reaction solution was stirred at room temperature for 14 hr, and ethyl acetate (100 mL) was added thereto. The organic layer was washed with cold water (2×25 mL) and saturated brine (2×25 mL), and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC to give the title compound (0.285 g, 51%) as a white powder. The reaction solution was stirred at room temperature for 14 hr The organic layer was washed with cold water (2×25 mL) and saturated brine (2×25 mL) dried the solvent was evaporated under reduced pressure The obtained residue was purified by preparative HPLC

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

Procedure: To a solution of N-(9-ethyl-9H-carbazol-3-yl)-5-hydroxy-3-methylpentanamine (0.40 g, 1.23 mmol) in DMF (10.0 mL) was added potassium-t-butoxide (0.304 g, 2.71 mmol) under argon atmosphere. The mixture was stirred at room temperature for 15 min, and 4-fluorophthalonitrile (0.270 g, 1.85 mmol) was added thereto. The reaction solution was stirred at room temperature for 14 hr, and ethyl acetate (100 mL) was added thereto. The organic layer was washed with cold water (2×25 mL) and saturated brine (2×25 mL), and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by preparative HPLC to give the title compound (0.285 g, 51%) as a white powder. The reaction solution was stirred at room temperature for 14 hr The organic layer was washed with cold water (2×25 mL) and saturated brine (2×25 mL) dried the solvent was evaporated under reduced pressure The obtained residue was purified by preparative HPLC

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

Procedure: Using 4-fluorophthalonitrile (500 mg), (2S,3S)-3-(1-hydroxy-1-methylethyl)-2-methylpyrrolidine 1/2 oxalate (870 mg) and lithium carbonate (341 mg), the title compound was obtained as a yellow solid (yield: 42 mg) by an operation similar to that in Example 3.

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

Procedure: The compound obtained using 2-{[4-(2-aminoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester synthesized in Example 7 and 4-fluorophthalonitrile as starting materials and by operations similar to those of Example 265-1 and Example 265-2 was treated with dichloromethane and trifluoroacetic acid, and the mixture was stirred at room temperature for 12 hr. The reaction solution was concentrated under reduced pressure, and the residue was purified by high performance liquid chromatography (elution solvent; 0.05% trifluoroacetic acid-water:0.05% trifluoroacetic acid-acetonitrile) to give the title compound. The compound obtained The reaction solution was concentrated under reduced pressure the residue was purified by high performance liquid chromatography (elution solvent; 0.05% trifluoroacetic acid-water:0.05% trifluoroacetic acid-acetonitrile)