2-(azepan-1-yl)ethanamine

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 mixture of 20.06 g (0.098 mole) of [(2-chloroethyl)sulfonyl]benzene 15.44 g (0.109 mole) of N-(2-aminoethyl)homopiperidine, and 15.0 g (0.149 mole) of triethylamine in 800 ml of acetonitrile was stirred at room temperature for 18 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and water. The methylene chloride solution was dried over magnesuim sulfate, and the solvent waas removed in vacuo to give an oil. This was dissolved in methanol, and the solution was treated with a solution of 2 equivalents of maleic acid (25.52 g, 0.22 mole) in methanol. A white solid precipitated at room temperature to give 32.3 g (60.7%) of title compound as a white solid; mp 144°-146° C. The solvent was removed in vacuo the residue was partitioned between methylene chloride and water The methylene chloride solution was dried over magnesuim sulfate the solvent waas removed in vacuo to give an oil A white solid precipitated at room temperature

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

実験手順: To a solution of 5.0 g (0.03 mole) of 1,1'-carbonyldiimidazole in 75 ml of tetrahydrofuran (THF) was added a solution of 4.0 g (0.028 mole) of N-(2-aminoethyl)homopiperidine in 75 ml of THF, and the reaction mixture was stirred at ambient temperature for 1.5 hr. A solution of 5.0 g (0.03 mole) of 1-phenylpiperazine in 50 ml of THF was added, and the reaction mixture was heated at reflux for 20 hr. The solution was concentrated under reduced pressure, and the residue was dissolved in 150 ml of benzene. The solution was washed thrice with 50 ml portions of water and once with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oil, which was converted to the hydrochloride with ethereal hydrogen chloride. The collected solid was recrystallized from 2-propanol to yield 6.7 g (53%) of title compound as a white solid, m.p. 190°-193° C. the reaction mixture was heated at reflux for 20 hr The solution was concentrated under reduced pressure the residue was dissolved in 150 ml of benzene The solution was washed thrice with 50 ml portions of water once with brine, dried over anhydrous sodium sulfate concentrated under reduced pressure to give an oil, which The collected solid was recrystallized from 2-propanol

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

実験手順: A mixture of 20.06 g (0.098 mole) of [(2-chloroethyl)sulfonyl]benzene 15.44 g (0.109 mole) of N-(2-aminoethyl)homopiperidine, and 15.0 g (0.149 mole) of triethylamine in 800 ml of acetonitrile was stirred at room temperature for 18 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and water. The methylene chloride solution was dried over magnesuim sulfate, and the solvent waas removed in vacuo to give an oil. This was dissolved in methanol, and the solution was treated with a solution of 2 equivalents of maleic acid (25.52 g, 0.22 mole) in methanol. A white solid precipitated at room temperature to give 32.3 g (60.7%) of title compound as a white solid; mp 144°-146° C. The solvent was removed in vacuo the residue was partitioned between methylene chloride and water The methylene chloride solution was dried over magnesuim sulfate the solvent waas removed in vacuo to give an oil A white solid precipitated at room temperature

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

実験手順: A mixture of 20.06 g (0.098 mole) of [(2-chloroethyl)sulfonyl]benzene 15.44 g (0.109 mole) of N-(2-aminoethyl)homopiperidine, and 15.0 g (0.149 mole) of triethylamine in 800 ml of acetonitrile was stirred at room temperature for 18 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and water. The methylene chloride solution was dried over magnesuim sulfate, and the solvent waas removed in vacuo to give an oil. This was dissolved in methanol, and the solution was treated with a solution of 2 equivalents of maleic acid (25.52 g, 0.22 mole) in methanol. A white solid precipitated at room temperature to give 32.3 g (60.7%) of title compound as a white solid; mp 144°-146° C. The solvent was removed in vacuo the residue was partitioned between methylene chloride and water The methylene chloride solution was dried over magnesuim sulfate the solvent waas removed in vacuo to give an oil A white solid precipitated at room temperature

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

実験手順: A mixture of nitrile 290 (5.58 g, 40.4 mmol) and Raney Nickel (50% w/w in water, ca. 5 mL) in EtOH (50 mL) and cNH3 (4 mL) was stirred under H2 (60 psi) for 16 h. The mixture was filtered through Celite, washed with EtOH (3×10 mL) and the solvent evaporated to give crude diamine 291 as an oil (2.03 g, 35%) which was used without further purification: 1H NMR δ 2.72 (t, J=6.1 Hz, 2H, CH2N), 2.60-2.68 (m, 4H, 2×CH2N), 2.53 (t, J=6.1 Hz, 2H, CH2N), 1.55-1.66 (m, 10H, 4×CH2, NH2). The mixture was filtered through Celite washed with EtOH (3×10 mL) the solvent evaporated

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Azepane (289) (4.9 mL, 43.8 mmol) was added dropwise to a stirred aqueous solution of glycolonitrile (55%, 5.0 g, 48.2 mmol) at 5° C. and the solution was stirred at 70° C. for 30 min. The solution was cooled, diluted with water (20 mL), washed with Et2O (3×50 mL). The organic fraction was dried and the solvent evaporated to give nitrile 290 (5.58 g, 92%) as a colourless oil: 1H NMR δ 3.56 (s, 2H, CH2CN), 2.71 (br dd, J=5.8, 5.5 Hz, 4H, 2×CH2N), 1.67-1.73 (m, 4H, 2×CH2), 1.59-1.64 (m, 4H, 2×CH2). The solution was cooled washed with Et2O (3×50 mL) The organic fraction was dried the solvent evaporated

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

実験手順: 2-(1-Azepanyl)ethylamine (289) (0.52 g, 3.6 mmol) was added to a stirred solution of chloride 21 (322 mg, 1.5 mmol) in DME (30 mL) and the solution stirred at reflux temperature for 3 h. The solvent was evaporated and the residue partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL). The organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give 1-oxide 46 (264 mg, 56%) as a yellow solid: mp (MeOH) 121-123° C.; 1H NMR δ 8.08 (s, 1H, H-9), 7.40 (s, 1H, H-5), 5.93 (br s, 1H, NH), 3.47-3.52 (m, 2H, CH2N), 2.97-3.03 (m, 4H, H-6, H-8), 2.74 (dd, J=6.0, 5.8 Hz, 2H, CH2N), 2.65-2.68 (m, 4H, 2×CH2N), 2.15 (p, J=7.4 Hz, 2H, H-7), 1.58-1.68 (m, 8H, 4×CH2); 13C NMR δ 158.8, 154.5, 148.8, 143.1, 129.7, 120.5, 114.6, 55.9, 55.1 (2), 38.8, 33.1, 32.3, 28.4 (2), 26.9 (2), 25.7. Anal. calcd for C18H25N5O: C, 66.0; H, 7.7; N, 21.4. Found: C, 66.0; H, 7.6; N, 21.5%. at reflux temperature for 3 h The solvent was evaporated the residue partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL) The organic fraction was dried the solvent evaporated The residue was purified by chromatography eluting with a gradient (0-10%) of MeOH/DCM

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

実験手順: 2-Azepan-1-ylethylamine (0.04 mL) and 4-[2-(3-chlorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl]pyrimidin-2-yl methyl sulfone (0.02 g) were mixed at room temperature and heated with an airgun until a homogenous melt was obtained (2 min). Upon cooling, water was added. The precipitated solid was filtered and dried to give the title compound as a beige solid (0.014 g); 1H NMR (d6-DMSO) δ 9.51(1H, s), 8.49(1H, bs), 8.16(1H, d), 7.70–7.65(2H, m), 7.60–7.50(3H, m), 7.00(1H, bs), 6.36(1H, bs), 2.6(6H, bs), 1.6(8H, bs); m/z 515(M+1)+. heated with an airgun until a homogenous melt was obtained (2 min) Upon cooling The precipitated solid was filtered dried

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

実験手順: To a solution of 5.0 g (0.03 mole) of 1,1'-carbonyldiimidazole in 75 ml of tetrahydrofuran (THF) was added a solution of 4.0 g (0.028 mole) of N-(2-aminoethyl)homopiperidine in 75 ml of THF, and the reaction mixture was stirred at ambient temperature for 1.5 hr. A solution of 5.0 g (0.03 mole) of 1-phenylpiperazine in 50 ml of THF was added, and the reaction mixture was heated at reflux for 20 hr. The solution was concentrated under reduced pressure, and the residue was dissolved in 150 ml of benzene. The solution was washed thrice with 50 ml portions of water and once with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oil, which was converted to the hydrochloride with ethereal hydrogen chloride. The collected solid was recrystallized from 2-propanol to yield 6.7 g (53%) of title compound as a white solid, m.p. 190°-193° C. the reaction mixture was heated at reflux for 20 hr The solution was concentrated under reduced pressure the residue was dissolved in 150 ml of benzene The solution was washed thrice with 50 ml portions of water once with brine, dried over anhydrous sodium sulfate concentrated under reduced pressure to give an oil, which The collected solid was recrystallized from 2-propanol

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

実験手順: A mixture of 20.06 g (0.098 mole) of [(2-chloroethyl)sulfonyl]benzene 15.44 g (0.109 mole) of N-(2-aminoethyl)homopiperidine, and 15.0 g (0.149 mole) of triethylamine in 800 ml of acetonitrile was stirred at room temperature for 18 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and water. The methylene chloride solution was dried over magnesuim sulfate, and the solvent waas removed in vacuo to give an oil. This was dissolved in methanol, and the solution was treated with a solution of 2 equivalents of maleic acid (25.52 g, 0.22 mole) in methanol. A white solid precipitated at room temperature to give 32.3 g (60.7%) of title compound as a white solid; mp 144°-146° C. The solvent was removed in vacuo the residue was partitioned between methylene chloride and water The methylene chloride solution was dried over magnesuim sulfate the solvent waas removed in vacuo to give an oil A white solid precipitated at room temperature