1-(1-bromopropan-2-yl)-4-fluorobenzene

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:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-(4-Piperazinyl)indoline (0.20 g) was dissolved in dimethylformamide (3 ml) and 4-(2-bromo-1-methylethyl)fluorobenzene (10.0 g) and triethylamine (0.14 ml) were added to the resultant solution followed by stirring at 60° C. overnight. After adding water, the liquid reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. After evaporating the solvent, the resulting residue was purified by NH-silica gel column chromatography (methanol/methylene chloride system) to give the title compound (178 mg) as an oil. the liquid reaction mixture was extracted with ethyl acetate The organic layer was washed with brine dried over magnesium sulfate After evaporating the solvent the resulting residue was purified by NH-silica gel column chromatography (methanol/methylene chloride system)

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

実験手順: A mixture of (±)-2-(4-fluorophenyl)propyl bromide (3.03 g, 13.96 mmol), N-Boc-piperazine (2.60 g, 13.96 mmol), potassium carbonate (3.86 g, 27.93 mmol) and sodium iodide (2.09 g, 13.96 mmol), in anhydrous isopropyl alcohol (100 ml) was refluxed for 16 h. The inorganics were filtered off and the solvent evaporated in vacuo. The resulting residue was partitioned between CH2Cl2 (3×150 ml) and water (50 ml). The combined extracts were dried (Na2SO4) and evaporated and the residue chromatographed on silica gel eluting with hexane to give 1.8 g (40%) of product. This material was dissolved in 99% formic acid (50 ml) and the solution stirred at room temperature for 16 h. The solvent was removed under vacuum and the residue basified by addition of saturated K2CO3 solution and then extracted with n-butanol (100 ml). The n-butanol was evaporated in vacuo and the residue chromatographed on silica gel eluting with CH2Cl2 /MeOH/NH3 (60:8:1) to give the title-product (0.34 g, 27%), δ(360 MHz, CDCl3) 1.24 (3H, d, J=7.0 Hz, Me), 2.30-2.46 (6H, m, 3 of CH2), 2.78-2.98 (5H, m, 2 of CH2 and CH), 6.94-7.00 (2H, m, Ar--H), 7.12-7.26 (2H, m, Ar--H). The inorganics were filtered off the solvent evaporated in vacuo The resulting residue was partitioned between CH2Cl2 (3×150 ml) and water (50 ml) The combined extracts were dried (Na2SO4) evaporated the residue chromatographed on silica gel eluting with hexane

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

実験手順: A mixture of Intermediate 3 (0.31 g, 1.0 mmol), 2-(4-fluorophenyl)propyl bromide (0.228 g, 1.05 mmol), triethylamine (0.202 g, 2.0 mmol) and sodium iodide (0.165 g, 1.1 mmol), in DMF (20 ml) was heated at 90° C., with stirring, for 16 h. The mixture was cooled to room temperature and partitioned between dichloromethane and water. The CH2Cl2 layer was separated, dried (Na2SO4) and evaporated under vacuum. The crude product was chromatographed through silica gel eluting with CH2Cl2 /MeOH/NH3 (90:10:1) to give the title-indole (0.125 g, 28%). The 3.0 hydrogen oxalate monohydrate salt was prepared, mp 203-205° C., (Found: C, 52.11; H, 5.60; N, 11.45. C26H31N6F. 3.0 (C2H2O4) 1.0H2O requires C, 52.31; H, 5.35; N, 11.44%), δ(360 MHz, D6 -DMSO) 1.17 (3H, d, J=6.8 Hz, Me), 1.92-2.06 (2H, m, CH2), 2.44-3.26 (15H, m, 7 of CH2 and CH), 7.08-7.13 (2H, m, Ar--H), 7.26-7.33 (4H, m, Ar--H), 7.50 (1H, d, J=8.6 Hz, Ar--H), 7.78 (1H, d, J=1.5 Hz, Ar--H), 9.01 (2H, s, Ar--H), 11.16 (1H, s, NH). partitioned between dichloromethane and water The CH2Cl2 layer was separated dried (Na2SO4) evaporated under vacuum The crude product was chromatographed through silica gel eluting with CH2Cl2 /MeOH/NH3 (90:10:1)