3-(2-chlorophenoxy)azetidine;hydrochloride

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

実験手順: DIPEA (143 mg, 1.1 mmol) followed by HOBt (39 mg, 0.29 mmol) and EDCI (56 mg, 0.29 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (67 g, 0.27 mmol) in DMF (2 mL). After 2 minutes of stirring, 3-(2-chloro-phenoxy)-azetidinehydrochloride (prepared by the method used for the synthesis of Intermediate 71) (60 mg, 0.27 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between cold water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative HPLC afforded 48 mg (42.8% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 411, 99.1%. 1H NMR (300 MHz, DMSO-d6): δ 13.7 (s, 1H), 8.2 (t, 1H), 7.54 (m, 2H), 7.28 (m, 5H), 7.08 (d, 1H), 7.0 (t, 1H), 6.86 (d, 1H), 5.1 (m, 1H), 4.64 (m, 1H), 4.36 (m, 1H), 4.2 (m, 1H), 3.84 (m, 3H). was added the resulting mixture was stirred at room temperature overnight The reaction mixture was partitioned between cold water and ethyl acetate The organic layer was dried over sodium sulfate concentrated under reduced pressure Purification by preparative HPLC

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

実験手順: DIPEA (141 mg, 1.1 mmol) followed by HOBt (39 mg, 0.29 mmol) and EDCI (56 mg, 0.29 mmol) were added to a stirred solution of [(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 3-aminopyridine, and subsequently, application of Step 3 of the General Scheme) (67.5 mg, 0.27 mmol) in DMF (3 mL). After 2 minutes of stirring, 3-(2-chloro-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (60 mg, 0.27 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between cold water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative HPLC afforded 33 mg (29.4% Yield) of 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 413, 98.7%. 1H NMR (300 MHz, DMSO-d6): δ 9.42 (s, 1H), 9.2 (d, 1H), 8.7 (m, 2H), 8.4 (m, 1H), 7.64 (m, 1H), 7.42 (m, 1H), 7.24 (m, 1H), 7.0 (t, 1H), 6.9 (d, 1H), 5.12 (m, 1H), 4.68 (m, 1H), 4.38 (m, 1H), 4.24 (m, 1H), 3.96 (m, 1H), 3.84 (m, 1H). prepared by the method was added the resulting mixture was stirred at room temperature overnight The reaction mixture was partitioned between cold water and ethyl acetate The organic layer was dried over sodium sulfate concentrated under reduced pressure Purification by preparative HPLC

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

実験手順: DIPEA (141 mg, 1.09 mmol) was added to a stirred solution of [(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid (prepared from Intermediate 68 by means of Step 3 of the General Scheme) (67 mg, 0.27 mmol) in DMF (3 mL) followed by HOBt (39 mg, 0.28 mmol) and EDCI (56 mg, 0.28 mmol). After 2 minutes of stirring, 3-(2-chloro-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (60 mg, 0.27 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. Partitioning with cold water and ethyl acetate and concentration of the organic layer after drying over sodium sulfate afforded a residue which was purified by column chromatography (using silica gel 60-120 and 100% EtOAc as eluent) to afford 30 mg (26.7% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 411, 98.45%. 1H NMR (300 MHz, DMSO-d6): δ 8.34 (d, 1H), 8.28 (d, 1H), 8.12 (t, 1H), 7.72 (d, 1H), 7.44 (m, 3H), 7.38 (m, 1H), 7.26 (m, 1H), 6.8 (m, 1H), 6.7 (d, 1H), 5.1 (m, 1H), 4.7 (m, 1H), 4.4 (m, 1H), 4.2 (m, 1H), 3.8 (m, 3H). was added the resulting mixture was stirred at ambient temperature overnight Partitioning with cold water and ethyl acetate and concentration of the organic layer after drying over sodium sulfate afforded a residue which was purified by column chromatography (using silica gel 60-120 and 100% EtOAc as eluent)

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

実験手順: DIPEA (143 mg, 1.1 mmol) followed by HOBt (39 mg, 0.29 mmol) and EDCI (56 mg, 0.29 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (67 g, 0.27 mmol) in DMF (2 mL). After 2 minutes of stirring, 3-(2-chloro-phenoxy)-azetidinehydrochloride (prepared by the method used for the synthesis of Intermediate 71) (60 mg, 0.27 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between cold water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative HPLC afforded 48 mg (42.8% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 411, 99.1%. 1H NMR (300 MHz, DMSO-d6): δ 13.7 (s, 1H), 8.2 (t, 1H), 7.54 (m, 2H), 7.28 (m, 5H), 7.08 (d, 1H), 7.0 (t, 1H), 6.86 (d, 1H), 5.1 (m, 1H), 4.64 (m, 1H), 4.36 (m, 1H), 4.2 (m, 1H), 3.84 (m, 3H). was added the resulting mixture was stirred at room temperature overnight The reaction mixture was partitioned between cold water and ethyl acetate The organic layer was dried over sodium sulfate concentrated under reduced pressure Purification by preparative HPLC

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

実験手順: DIPEA (141 mg, 1.1 mmol) followed by HOBt (39 mg, 0.29 mmol) and EDCI (56 mg, 0.29 mmol) were added to a stirred solution of [(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 3-aminopyridine, and subsequently, application of Step 3 of the General Scheme) (67.5 mg, 0.27 mmol) in DMF (3 mL). After 2 minutes of stirring, 3-(2-chloro-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (60 mg, 0.27 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between cold water and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative HPLC afforded 33 mg (29.4% Yield) of 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 413, 98.7%. 1H NMR (300 MHz, DMSO-d6): δ 9.42 (s, 1H), 9.2 (d, 1H), 8.7 (m, 2H), 8.4 (m, 1H), 7.64 (m, 1H), 7.42 (m, 1H), 7.24 (m, 1H), 7.0 (t, 1H), 6.9 (d, 1H), 5.12 (m, 1H), 4.68 (m, 1H), 4.38 (m, 1H), 4.24 (m, 1H), 3.96 (m, 1H), 3.84 (m, 1H). prepared by the method was added the resulting mixture was stirred at room temperature overnight The reaction mixture was partitioned between cold water and ethyl acetate The organic layer was dried over sodium sulfate concentrated under reduced pressure Purification by preparative HPLC

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

実験手順: DIPEA (141 mg, 1.09 mmol) was added to a stirred solution of [(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid (prepared from Intermediate 68 by means of Step 3 of the General Scheme) (67 mg, 0.27 mmol) in DMF (3 mL) followed by HOBt (39 mg, 0.28 mmol) and EDCI (56 mg, 0.28 mmol). After 2 minutes of stirring, 3-(2-chloro-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (60 mg, 0.27 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. Partitioning with cold water and ethyl acetate and concentration of the organic layer after drying over sodium sulfate afforded a residue which was purified by column chromatography (using silica gel 60-120 and 100% EtOAc as eluent) to afford 30 mg (26.7% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 411, 98.45%. 1H NMR (300 MHz, DMSO-d6): δ 8.34 (d, 1H), 8.28 (d, 1H), 8.12 (t, 1H), 7.72 (d, 1H), 7.44 (m, 3H), 7.38 (m, 1H), 7.26 (m, 1H), 6.8 (m, 1H), 6.7 (d, 1H), 5.1 (m, 1H), 4.7 (m, 1H), 4.4 (m, 1H), 4.2 (m, 1H), 3.8 (m, 3H). was added the resulting mixture was stirred at ambient temperature overnight Partitioning with cold water and ethyl acetate and concentration of the organic layer after drying over sodium sulfate afforded a residue which was purified by column chromatography (using silica gel 60-120 and 100% EtOAc as eluent)