(5-bromo-2-fluorophenyl)methanamine;hydrochloride

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

実験手順: 40.0 mg (0.144 mmol) of [3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-acetic acid from Example 93A, 36.0 mg (0.150 mmol) of 5-bromo-2-fluorobenzylamine hydrochloride, 22.1 mg (0.163 mmol) of HOBt and 17.6 mg (0.136 mmol) of N,N-diisopropyl-ethylamine are placed in 1.5 ml of dimethylformamide and treated with 33.9 mg (0.177 mmol) of EDC hydrochloride. This is stirred overnight at room temperature, then diluted with 15 ml of water and extracted with ethyl acetate. After evaporation of the organic phase, the crude product is purified by preparative HPLC [Method 13]. 21 mg (32% of theory) of the target compound are thus obtained. extracted with ethyl acetate After evaporation of the organic phase the crude product is purified by preparative HPLC [Method 13] 21 mg (32% of theory) of the target compound are thus obtained

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

実験手順: 40.0 mg (0.144 mmol) of [3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-acetic acid from Example 93A, 36.0 mg (0.150 mmol) of 5-bromo-2-fluorobenzylamine hydrochloride, 22.1 mg (0.163 mmol) of HOBt and 17.6 mg (0.136 mmol) of N,N-diisopropyl-ethylamine are placed in 1.5 ml of dimethylformamide and treated with 33.9 mg (0.177 mmol) of EDC hydrochloride. This is stirred overnight at room temperature, then diluted with 15 ml of water and extracted with ethyl acetate. After evaporation of the organic phase, the crude product is purified by preparative HPLC [Method 13]. 21 mg (32% of theory) of the target compound are thus obtained. extracted with ethyl acetate After evaporation of the organic phase the crude product is purified by preparative HPLC [Method 13] 21 mg (32% of theory) of the target compound are thus obtained

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

実験手順: Add ethyl chloroformate (0.24 mL, 2.49 mmol) to a solution of 5-bromo-2-fluorobenzylamine hydrochloride (500 mg, 2.08 mmol) in dichloromethane (8 mL) and diisopropylethylamine (0.90 mL, 5.20 mmol). After 3 h dilute the reaction with diethyl ether and wash twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate to give the title compound as a colorless oil (0.527 g, 92%). After 3 h dilute wash twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride Dry (sodium sulfate) filter concentrate

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

実験手順: Add ethyl chloroformate (0.24 mL, 2.49 mmol) to a solution of 5-bromo-2-fluorobenzylamine hydrochloride (500 mg, 2.08 mmol) in dichloromethane (8 mL) and diisopropylethylamine (0.90 mL, 5.20 mmol). After 3 h dilute the reaction with diethyl ether and wash twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate to give the title compound as a colorless oil (0.527 g, 92%). After 3 h dilute wash twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride Dry (sodium sulfate) filter concentrate

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

実験手順: Dissolve 5-bromo-2-fluorobenzylamine hydrochloride (500 mg, 2.08 mmol) in dichloromethane (8 mL) and diisopropylethylamine (0.90 mL, 5.20 mmol) and treat with methanesulfonyl chloride (0.19 mL, 2.49 mmol). After 4.5 h dilute with ethyl acetate and wash with 0.5 N hydrochloric acid, an aqueous saturated solution of sodium bicarbonate, and an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate to give the title compound as a pale orange oil, which crystallizes upon standing (573 mg, 98%). wash with 0.5 N hydrochloric acid Dry (sodium sulfate) filter concentrate

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

実験手順: Add acetyl chloride (0.18 mL, 2.49 mmol) to a mixture of 5-bromo-2-fluorobenzylamine hydrochloride (500 mg, 2.08 mmol) in dichloromethane (8 mL) and diisopropylethylamine (0.90 mL, 5.20 mmol) and stir 3 h. Dilute with diethyl ether and separate the layers. Wash the organic layer twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate to give the title compound as a white crystalline solid (490 mg, 96%). separate the layers Wash the organic layer twice with 1 N hydrochloric acid Dry (sodium sulfate) filter concentrate

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

実験手順: Add acetyl chloride (0.18 mL, 2.49 mmol) to a mixture of 5-bromo-2-fluorobenzylamine hydrochloride (500 mg, 2.08 mmol) in dichloromethane (8 mL) and diisopropylethylamine (0.90 mL, 5.20 mmol) and stir 3 h. Dilute with diethyl ether and separate the layers. Wash the organic layer twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate to give the title compound as a white crystalline solid (490 mg, 96%). separate the layers Wash the organic layer twice with 1 N hydrochloric acid Dry (sodium sulfate) filter concentrate

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 5-bromo-2-fluorobenzylamine hydrochloride (15.0 g, 62 mmol), methyl dimethoxyacetate (10.0 g, 75 mmol), and DIPEA (10.3 mL, 62 mmol) in methanol (15 mL) was heated at 60° C. for 16 h in a bomb apparatus. After cooling to RT, the solvent was evaporated and DCM (150 mL) was added. The solution was washed with water (2×30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. It was purified by column chromatography on silica gel using EtOAc/Hexanes (1:1) to give the title compound. 1H NMR (CDCl3, 300 MHz) δ=3.42 (s, 6H), 4.53 (d, J=4.8 Hz, 2H), 4.81 (s, 1H), 6.96 (t, J=6.8 Hz, 1H), 7.40-7.42 (m, 1H), 7.51-7.54 (m, 1H). MS(ES+): m/z=305.73/307.69 [MH+]. HPLC: tR=2.89 min (polar—5 min, ZQ2). After cooling to RT the solvent was evaporated DCM (150 mL) was added The solution was washed with water (2×30 mL) dried over Na2SO4 filtered concentrated under reduced pressure to give the crude product It was purified by column chromatography on silica gel

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

実験手順: 40.0 mg (0.144 mmol) of [3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-acetic acid from Example 93A, 36.0 mg (0.150 mmol) of 5-bromo-2-fluorobenzylamine hydrochloride, 22.1 mg (0.163 mmol) of HOBt and 17.6 mg (0.136 mmol) of N,N-diisopropyl-ethylamine are placed in 1.5 ml of dimethylformamide and treated with 33.9 mg (0.177 mmol) of EDC hydrochloride. This is stirred overnight at room temperature, then diluted with 15 ml of water and extracted with ethyl acetate. After evaporation of the organic phase, the crude product is purified by preparative HPLC [Method 13]. 21 mg (32% of theory) of the target compound are thus obtained. extracted with ethyl acetate After evaporation of the organic phase the crude product is purified by preparative HPLC [Method 13] 21 mg (32% of theory) of the target compound are thus obtained

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

実験手順: Add ethyl chloroformate (0.24 mL, 2.49 mmol) to a solution of 5-bromo-2-fluorobenzylamine hydrochloride (500 mg, 2.08 mmol) in dichloromethane (8 mL) and diisopropylethylamine (0.90 mL, 5.20 mmol). After 3 h dilute the reaction with diethyl ether and wash twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate to give the title compound as a colorless oil (0.527 g, 92%). After 3 h dilute wash twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride Dry (sodium sulfate) filter concentrate

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

実験手順: Dissolve 5-bromo-2-fluorobenzylamine hydrochloride (500 mg, 2.08 mmol) in dichloromethane (8 mL) and diisopropylethylamine (0.90 mL, 5.20 mmol) and treat with methanesulfonyl chloride (0.19 mL, 2.49 mmol). After 4.5 h dilute with ethyl acetate and wash with 0.5 N hydrochloric acid, an aqueous saturated solution of sodium bicarbonate, and an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate to give the title compound as a pale orange oil, which crystallizes upon standing (573 mg, 98%). wash with 0.5 N hydrochloric acid Dry (sodium sulfate) filter concentrate

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

実験手順: Add acetyl chloride (0.18 mL, 2.49 mmol) to a mixture of 5-bromo-2-fluorobenzylamine hydrochloride (500 mg, 2.08 mmol) in dichloromethane (8 mL) and diisopropylethylamine (0.90 mL, 5.20 mmol) and stir 3 h. Dilute with diethyl ether and separate the layers. Wash the organic layer twice with 1 N hydrochloric acid and once with an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate to give the title compound as a white crystalline solid (490 mg, 96%). separate the layers Wash the organic layer twice with 1 N hydrochloric acid Dry (sodium sulfate) filter concentrate