1-[2-(trifluoromethoxy)phenyl]piperazine

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:

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

実験手順: A mixture comprising 0.459 g of Compound 1B, 0.445 g of 1-(2-trifluoromethoxyphenyl)piperaine (prepared as described by D. Clarke et al, in European Patent EP 711 757, 1996), 0.634 g sodium triacetoxyborohydride, 0.23 mL of glacial acetic acid and 15 mL of 1,2-dichloroethane was stirred for 4 h, under a nitrogen atmosphere. The resultant solution was then kept overnight at room temperature, followed by the addition of 10 mL of water, and alkalinization with a 20% aqueous Na2CO3 solution. This was followed by separation of phases, with the isolated aqueous phase being extracted with 2×20 mL dichloromethane, and with the collected organic phases being dried over anhydrous sodium sulphate. This was followed by the removal of solvents, via vacuum evaporation to dryness. The obtained product residue was purified by flash chromatography (ethyl acetate—petroleum ether gradient 90:10 to 10:0). This was followed by evaporation of the solvents, affording 0.44 g of the title compound (yield 51%). This was followed by separation of phases, with the isolated aqueous phase being extracted with 2×20 mL dichloromethane with the collected organic phases being dried over anhydrous sodium sulphate This was followed by the removal of solvents, via vacuum evaporation to dryness The obtained product residue was purified by flash chromatography (ethyl acetate—petroleum ether gradient 90:10 to 10:0) This was followed by evaporation of the solvents

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

実験手順: Compound 9 was prepared using the method described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-trifluoromethoxyphenyl)piperazine (0.70 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 9 (0.45 g, 32%); C28H33ClF3N3O2, LRMS (m/z)=537 (MH+). Compound 9 was prepared

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

実験手順: Compound 9 was prepared using the method described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-trifluoromethoxyphenyl)piperazine (0.70 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 9 (0.45 g, 32%); C28H33ClF3N3O 2, LRMS (m/z)=537 (MH+). Compound 9 was prepared

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: Compound 9 was prepared using the method described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-trifluoromethoxyphenyl)piperazine (0.70 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 9 (0.45 g, 32%); C28H33ClF3N3O 2, LRMS (m/z)=537 (MH+). Compound 9 was prepared

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of 1.23 g of 1-(2-trifluoromethoxyphenyl)piperazine, 0.73 mL of 97% 2-bromoethanol, 1.25 mL of DIPEA and 4 mL of DMF was heated at 65° C. for 6 h. After cooling to r.t., the mixture was diluted with H2O (50 mL) and extracted with CH2Cl2 (3×30 mL). The organic layer was dried (anhydrous Na2SO4) and evaporated to dryness in vacuo. The residue was purified by flash chromatography (CH2Cl2-MeOH 100:1.5) affording 0.911 g (63%) of the title compound. After cooling to r.t. extracted with CH2Cl2 (3×30 mL) The organic layer was dried (anhydrous Na2SO4) evaporated to dryness in vacuo The residue was purified by flash chromatography (CH2Cl2-MeOH 100:1.5)

反応条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was obtained following the procedure described for example 54, but using 1-(2-trifluoromethoxyphenyl)piperazine in place of 1-(4-nitro-2-methoxyphenyl)piperazine. The reaction mixture was heated at 120° C. for 8 h. The residue obtained by usual work-up and extraction with Et2O was purified by flash chromatography (petroleum ether-EtOAc gradient from 90:10 to 80:20) to afford the title compound. Yield: 41%. was purified by flash chromatography (petroleum ether-EtOAc gradient from 90:10 to 80:20)

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

実験手順: Compound 9 was prepared using the method described in Example 3, starting with compound 2 (1.0 g, 2.60 mmol), 1-(2-trifluoromethoxyphenyl)piperazine (0.70 g, 2.86 mmol), and cesium carbonate (1.27 g, 3.90 mmol) to give 9 (0.45 g, 32%); C28H33ClF3N3O2, LRMS (m/z)=537 (MH+). Compound 9 was prepared

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

実験手順: A mixture comprising 0.459 g of Compound 1B, 0.445 g of 1-(2-trifluoromethoxyphenyl)piperaine (prepared as described by D. Clarke et al, in European Patent EP 711 757, 1996), 0.634 g sodium triacetoxyborohydride, 0.23 mL of glacial acetic acid and 15 mL of 1,2-dichloroethane was stirred for 4 h, under a nitrogen atmosphere. The resultant solution was then kept overnight at room temperature, followed by the addition of 10 mL of water, and alkalinization with a 20% aqueous Na2CO3 solution. This was followed by separation of phases, with the isolated aqueous phase being extracted with 2×20 mL dichloromethane, and with the collected organic phases being dried over anhydrous sodium sulphate. This was followed by the removal of solvents, via vacuum evaporation to dryness. The obtained product residue was purified by flash chromatography (ethyl acetate—petroleum ether gradient 90:10 to 10:0). This was followed by evaporation of the solvents, affording 0.44 g of the title compound (yield 51%). This was followed by separation of phases, with the isolated aqueous phase being extracted with 2×20 mL dichloromethane with the collected organic phases being dried over anhydrous sodium sulphate This was followed by the removal of solvents, via vacuum evaporation to dryness The obtained product residue was purified by flash chromatography (ethyl acetate—petroleum ether gradient 90:10 to 10:0) This was followed by evaporation of the solvents