1-methylcyclohexan-1-amine

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: A solution of 1,3-propanesultone (5.00 g, 40 mmol) in toluene (10 mL) was added dropwise to a the crude solution of 1-methyl-1-cyclohexylamine in MTBK (total volume 30 mL). The mixture was heated to reflux for 18 hours then cooled to room temperature. The solid was collected by suction filtration, rinsed with acetone (2×8 mL). The solid was dried overnight at 45° C. in the vacuum oven. The title compound was obtained as a fine white solid (9.22 g). However, the proton NMR and the ES-MS were not clean. The solid was suspended in methanol (45 mL) and the suspension was warmed to reflux. Water (12 mL) was added dropwise until a clear yellow solution was obtained. The mixture was slowly cool to room temperature with stirring. The solid was collected by suction-filtration, rinsed with methanol (2×5 mL). Another crop was collected from the filtrate. Both crops were dried overnight at 45° C. in the vacuum oven. The title compound was obtained as a fine white solid (6.82 g, 29.0 mmol, 66% overall yield). Both crops were identical and were mixed for submitting the compound. 1H NMR (500 MHz, D2O) δ 1.04-1.11 (m, 1H), 1.19 (s, 3H), 1.31 (q, J=12.2 Hz, 2H), 1.40 (qt, J=12.2 Hz, 2H), 1.46-1.62 (m, 2H), 1.63 (br d, J=11.7 Hz, 2H), 1.94 (q, J=7.3 Hz, 2H), 2.86 (t, J=7.1 Hz, 2H), 3.03 (t, J=7.6 Hz, 2H); 13C NMR (125 MHz, D2O) δ 19.1, 21.5, 22.0, 24.6, 34.1, 39.1, 48.2, 60.2; ES-MS 236 (M+H). The mixture was heated to reflux for 18 hours The solid was collected by suction filtration rinsed with acetone (2×8 mL) The solid was dried overnight at 45° C. in the vacuum oven

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

実験手順: A suspension of N-(4-chloromethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.1g), amino-methylcyclohexane (0.05g) and potassium carbonate (0.1g) in dimethylformamide (10ml) was stirred at room temperature overnight. The solvent was evaporated, and to the residue was added water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give N-(4-((cyclohexylmethyl)aminomethyl)-phenyl)-7-(4-methyl-phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 122) (0.06g) as colorless crystals. The solvent was evaporated to the residue was added water The mixture was extracted with ethyl acetate The organic layer was washed with water and saturated sodium chloride solution dried with anhydrous magnesium sulfate Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane

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

実験手順: A suspension of N-(4-chloromethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.1g), amino-methylcyclohexane (0.05g) and potassium carbonate (0.1g) in dimethylformamide (10ml) was stirred at room temperature overnight. The solvent was evaporated, and to the residue was added water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give N-(4-((cyclohexylmethyl)aminomethyl)-phenyl)-7-(4-methyl-phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 122) (0.06g) as colorless crystals. The solvent was evaporated to the residue was added water The mixture was extracted with ethyl acetate The organic layer was washed with water and saturated sodium chloride solution dried with anhydrous magnesium sulfate Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane

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

実験手順: A solution of 1,3-propanesultone (5.00 g, 40 mmol) in toluene (10 mL) was added dropwise to a the crude solution of 1-methyl-1-cyclohexylamine in MTBK (total volume 30 mL). The mixture was heated to reflux for 18 hours then cooled to room temperature. The solid was collected by suction filtration, rinsed with acetone (2×8 mL). The solid was dried overnight at 45° C. in the vacuum oven. The title compound was obtained as a fine white solid (9.22 g). However, the proton NMR and the ES-MS were not clean. The solid was suspended in methanol (45 mL) and the suspension was warmed to reflux. Water (12 mL) was added dropwise until a clear yellow solution was obtained. The mixture was slowly cool to room temperature with stirring. The solid was collected by suction-filtration, rinsed with methanol (2×5 mL). Another crop was collected from the filtrate. Both crops were dried overnight at 45° C. in the vacuum oven. The title compound was obtained as a fine white solid (6.82 g, 29.0 mmol, 66% overall yield). Both crops were identical and were mixed for submitting the compound. 1H NMR (500 MHz, D2O) δ 1.04-1.11 (m, 1H), 1.19 (s, 3H), 1.31 (q, J=12.2 Hz, 2H), 1.40 (qt, J=12.2 Hz, 2H), 1.46-1.62 (m, 2H), 1.63 (br d, J=11.7 Hz, 2H), 1.94 (q, J=7.3 Hz, 2H), 2.86 (t, J=7.1 Hz, 2H), 3.03 (t, J=7.6 Hz, 2H); 13C NMR (125 MHz, D2O) δ 19.1, 21.5, 22.0, 24.6, 34.1, 39.1, 48.2, 60.2; ES-MS 236 (M+H). The mixture was heated to reflux for 18 hours The solid was collected by suction filtration rinsed with acetone (2×8 mL) The solid was dried overnight at 45° C. in the vacuum oven

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Dissolve 1-methylcyclohexanamine (0.78 g, 6.89 mmol) in anhydrous THF (100 mL) and cool to 0° C. Add Et3N (3.49 g, 34.45 mmol) and 4-chlorobutanoyl chloride (1.94 g, 13.78 mmol) with stirring under N2. Stir the reaction mixture for 2 hours at room temperature and add water (100 mL). Extract the aqueous with EtOAc (3×200 mL) and then combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 30-80% of EtOAc-Hexane) to give 1.35 g (90%) of 4-chloro-N-(1-methylcyclohexyl)butanamide as a colorless oil. Extract the aqueous with EtOAc (3×200 mL) dry with Na2SO4 filter concentrate purify by flash column chromatography (silica gel, 30-80% of EtOAc-Hexane)

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

実験手順: A suspension of N-(4-chloromethylphenyl)-7—(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.1 g), amino-methylcyclohexane (0.05 g) and potassium carbonate (0.1 g) in dimethylformamide (10 ml) was stirred at room temperature over night. The solvent. was evaporated, and to the residue was added water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give N-(4—((cyclohexylmethyl)aminomethyl)phenyl)-7—(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 122) (0.06 g) as colorless crystals. was evaporated to the residue was added water The mixture was extracted with ethyl acetate The organic layer was washed with water and saturated sodium chloride solution dried with anhydrous magnesium sulfate Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane

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

実験手順: A suspension of N-(4-chloromethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.1 g), amino-methylcyclohexane (0.05 g) and potassium carbonate (0.1 g) in dimethylformamide (10 ml) was stirred at room temperature over night. The solvent was evaporated, and to the residue was added water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give N-(4-((cyclohexylmethyl)aminomethyl)phenyl)-7-(4-methyl-phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 122) (0.06 g) as colorless crystals. The solvent was evaporated to the residue was added water The mixture was extracted with ethyl acetate The organic layer was washed with water and saturated sodium chloride solution dried with anhydrous magnesium sulfate Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane

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

実験手順: A suspension of N-(4-chloromethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.1 g), amino-methylcyclohexane (0.05 g) and potassium carbonate (0.1 g) in dimethylformamide (10 ml) was stirred at room temperature over night. The solvent was evaporated, and to the residue was added water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give N-(4-((cyclohexylmethyl)aminomethyl)phenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 122) (0.06 g) as colorless crystals. The solvent was evaporated to the residue was added water The mixture was extracted with ethyl acetate The organic layer was washed with water and saturated sodium chloride solution dried with anhydrous magnesium sulfate Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane

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

実験手順: A suspension of N-(4-chloromethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.1g), amino-methylcyclohexane (0.05g) and potassium carbonate (0.1g) in dimethylformamide (10ml) was stirred at room temperature overnight. The solvent was evaporated, and to the residue was added water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, and dried with anhydrous magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give N-(4-((cyclohexylmethyl)aminomethyl)-phenyl)-7-(4-methyl-phenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 122) (0.06g) as colorless crystals. The solvent was evaporated to the residue was added water The mixture was extracted with ethyl acetate The organic layer was washed with water and saturated sodium chloride solution dried with anhydrous magnesium sulfate Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane

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

実験手順: A solution of 1,3-propanesultone (5.00 g, 40 mmol) in toluene (10 mL) was added dropwise to a the crude solution of 1-methyl-1-cyclohexylamine in MTBK (total volume 30 mL). The mixture was heated to reflux for 18 hours then cooled to room temperature. The solid was collected by suction filtration, rinsed with acetone (2×8 mL). The solid was dried overnight at 45° C. in the vacuum oven. The title compound was obtained as a fine white solid (9.22 g). However, the proton NMR and the ES-MS were not clean. The solid was suspended in methanol (45 mL) and the suspension was warmed to reflux. Water (12 mL) was added dropwise until a clear yellow solution was obtained. The mixture was slowly cool to room temperature with stirring. The solid was collected by suction-filtration, rinsed with methanol (2×5 mL). Another crop was collected from the filtrate. Both crops were dried overnight at 45° C. in the vacuum oven. The title compound was obtained as a fine white solid (6.82 g, 29.0 mmol, 66% overall yield). Both crops were identical and were mixed for submitting the compound. 1H NMR (500 MHz, D2O) δ 1.04-1.11 (m, 1H), 1.19 (s, 3H), 1.31 (q, J=12.2 Hz, 2H), 1.40 (qt, J=12.2 Hz, 2H), 1.46-1.62 (m, 2H), 1.63 (br d, J=11.7 Hz, 2H), 1.94 (q, J=7.3 Hz, 2H), 2.86 (t, J=7.1 Hz, 2H), 3.03 (t, J=7.6 Hz, 2H); 13C NMR (125 MHz, D2O) δ 19.1, 21.5, 22.0, 24.6, 34.1, 39.1, 48.2, 60.2; ES-MS 236 (M+H). The mixture was heated to reflux for 18 hours The solid was collected by suction filtration rinsed with acetone (2×8 mL) The solid was dried overnight at 45° C. in the vacuum oven