[4-(morpholin-4-ylmethyl)phenyl]methanamine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 4-(Morpholinomethyl)phenylmethylamine (8 g) and ethyl 3-(4-chlorophenyl) -2-hydroxyimino-3-oxopropionate (8.26 g) were dissolved in pyridine (120 ml) and the mixture was refluxed under heating for 12 hr. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography to give the objective ethyl 5-(4-chlorophenyl)-2-[4-(morpholinomethyl)phenyl]imidazole-4-carboxylate (8.46 g), melting point 183-185° C. the mixture was refluxed under heating for 12 hr The solvent was evaporated under reduced pressure

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

実験手順: N-(4-Morpholinomethylphenylmethyl)acetamide hydrochloride (28.4 g) was dissolved in 4N hydrochloric acid (114 ml) and the mixture was refluxed under heating for 3 hr 15 min. The solvent was evaporated and ethyl acetate was added. The resulting crystals were collected by filtration. The obtained crystals were dissolved in water (40 ml) and potassium carbonate was added to saturation, and the mixture was extracted with chloroform. The extract was dried over anhydrous sodium sulfate and, after drying, the solvent was evaporated under reduced pressure to give the objective 4-(morpholinomethyl)phenylmethylamine (17.4 g), melting point 47-49° C. the mixture was refluxed under heating for 3 hr 15 min The solvent was evaporated ethyl acetate was added The resulting crystals were collected by filtration The obtained crystals were dissolved in water (40 ml) potassium carbonate was added to saturation the mixture was extracted with chloroform The extract was dried over anhydrous sodium sulfate after drying the solvent was evaporated under reduced pressure

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

実験手順: Use a method similar to the General Procedure 1-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (400 mg, 0.94 mmol) with 4-(morpholin-4-ylmethyl)-benzylamine (291 mg, 1.41 mmol). Purify by chromatography on silica gel (80 g, pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 2:1 gradient) to obtain 7-chloro-6-[4-(morpholin-4-ylmethyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (304 mg, 67%). MS (APCI+) m/z: 482 (M+H)÷. Purify by chromatography on silica gel (80 g, pre-packed cartridge) eluting with hexane/EtOAc (1:0 to 2:1 gradient)

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

実験手順: Under a nitrogen atmosphere, add lithium aluminum hydride (1.13 g, 29.7 mmol) to THF (50 mL) at 0° C. followed by a solution of 4-(morpholin-4-ylmethyl)-benzonitrile (2 g, 9.89 mmol) in THF (10 mL). Stir at 0° C. for 1 h and at room temperature overnight. Cool the mixture to 0° C., and carefully add water (1.15 mL). Add diethyl ether (125 mL), 3N aqueous NaOH (1.15 mL), water (3.45 mL), and stir for 1 h at room temperature. Filter the solid residue and concentrate the filtrate in vacuo to obtain the title compound as a colorless oil (1.87 g, 94%). MS (APCI+) m/z: 207 (M+H)+. Cool the mixture to 0° C. Filter the solid residue concentrate the filtrate in vacuo

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

実験手順: To a suspension of 4-(morpholin-4-ylmethyl)benzonitrile (Description 122, 0.5 g, 2.5 mmol) in THF (7 mL) at 0° C. was added dropwise a solution of LiAlH4 (1.0 M in THF, 2.5 ml, 2.5 mmol). The reaction was stirred at 0° C. for 1 h. Additional LiAlH4 (1.0 M in THF, 1.0 ml, 1.0 mmol) was added and the reaction stirred for an additional 30 min. The reaction was quenched by the addition of water (0.13 mL) followed by 15% NaOH solution (0.13 ml) and stirred vigorously for 1 h. The reaction was filtered through celite, evaporated and azeotroped twice with toluene. The amine was used crude. the reaction stirred for an additional 30 min The reaction was quenched by the addition of water (0.13 mL) stirred vigorously for 1 h The reaction was filtered through celite evaporated azeotroped twice with toluene