3-methoxy-4-(2-pyrrolidin-1-ylethoxy)aniline

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

実験手順: A suspension of K2CO3 (235 mg, 1.70 mmol), 2-(bromomethyl)-1,3-dioxolane (400 mg, 1.70 mmol), and 3-methoxy-4-(2-(pyrrolidin-1-yl)ethoxy)benzenamine (3.0 g, 14.5 mmol), preparation described in PCT application WO 2002/101146, in DMSO (17 mL) was heated at 80° C. for 24 hr. After removal of any precipitate by filtration, the filtrate was partitioned between EtOAc/H2O (100/20 mL). The organic layer was washed with brine and dried over MgSO4. After removal of the solvent under vacuum, the residue was chromatographed on silica gel using 0%-20% gradient EtOAc/Hexanes to elute the title compound as a yellow brownish oil (150 mg, 27%) MS (ESI) 323 (M+H)+. After removal of any precipitate by filtration the filtrate was partitioned between EtOAc/H2O (100/20 mL) The organic layer was washed with brine dried over MgSO4 After removal of the solvent under vacuum the residue was chromatographed on silica gel using 0%-20% gradient EtOAc/Hexanes to elute the title compound as a yellow brownish oil (150 mg, 27%)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of K2CO3 (235 mg, 1.70 mmol), 2-(bromomethyl)-1,3-dioxolane (400 mg, 1.70 mmol), and 3-methoxy-4-(2-(pyrrolidin-1-yl)ethoxy)benzenamine (3.0 g, 14.5 mmol), preparation described in PCT application WO 2002/101146, in DMSO (17 mL) was heated at 80° C. for 24 hr. After removal of any precipitate by filtration, the filtrate was partitioned between EtOAc/H2O (100/20 mL). The organic layer was washed with brine and dried over MgSO4. After removal of the solvent under vacuum, the residue was chromatographed on silica gel using 0%-20% gradient EtOAc/Hexanes to elute the title compound as a yellow brownish oil (150 mg, 27%) MS (ESI) 323 (M+H)+. After removal of any precipitate by filtration the filtrate was partitioned between EtOAc/H2O (100/20 mL) The organic layer was washed with brine dried over MgSO4 After removal of the solvent under vacuum the residue was chromatographed on silica gel using 0%-20% gradient EtOAc/Hexanes to elute the title compound as a yellow brownish oil (150 mg, 27%)

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

実験手順: Following preparation as described in PCT application WO 2002/101146, 3-methoxy-4-(2-(pyrrolidin-1-yl)ethoxy)benzenamine (59 mg, 0.25 mol) was stirred overnight in DMF (2 mL) containing with 4-(4-chlorophenyl)-1H-pyrrole-2-carboxylic acid (65 mg, 0.25 mol), EDC (96 mg, 0.50 mol), HOBT (77 mg, 0.50 mol) and NaHCO3 (116 mg, 1.37 mol). After dilution of the reaction with 40 mL of EtOAc, the organic layer was washed with H2O (10 mL×2) and brine. The organic layer was dried over Na2SO4, and cone, in vacuum to a brown oil. The oil was purified by flash column chromatography (silica gel, CH3OH in CH2Cl2, 0-10% gradient) to yield 109 mg (99%) of the title compound as a colorless oil. MS (ESI) 440 (M+H)+. preparation the organic layer was washed with H2O (10 mL×2) and brine The organic layer was dried over Na2SO4, and cone, in vacuum to a brown oil The oil was purified by flash column chromatography (silica gel, CH3OH in CH2Cl2, 0-10% gradient)

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

実験手順: Following preparation as described in PCT application WO 2002/101146, 3-methoxy-4-(2-(pyrrolidin-1-yl)ethoxy)benzenamine (59 mg, 0.25 mol) was stirred overnight in DMF (2 mL) containing with 4-(4-chlorophenyl)-1H-pyrrole-2-carboxylic acid (65 mg, 0.25 mol), EDC (96 mg, 0.50 mol), HOBT (77 mg, 0.50 mol) and NaHCO3 (116 mg, 1.37 mol). After dilution of the reaction with 40 mL of EtOAc, the organic layer was washed with H2O (10 mL×2) and brine. The organic layer was dried over Na2SO4, and cone, in vacuum to a brown oil. The oil was purified by flash column chromatography (silica gel, CH3OH in CH2Cl2, 0-10% gradient) to yield 109 mg (99%) of the title compound as a colorless oil. MS (ESI) 440 (M+H)+. preparation the organic layer was washed with H2O (10 mL×2) and brine The organic layer was dried over Na2SO4, and cone, in vacuum to a brown oil The oil was purified by flash column chromatography (silica gel, CH3OH in CH2Cl2, 0-10% gradient)

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

実験手順: A suspension of K2CO3 (235 mg, 1.70 mmol), 2-(bromomethyl)-1,3-dioxolane (400 mg, 1.70 mmol), and 3-methoxy-4-(2-(pyrrolidin-1-yl)ethoxy)benzenamine (3.0 g, 14.5 mmol), preparation described in Patent: WO2002/101146, in DMSO (17 mL) was heated at 80° C. for 24 hr. After removal of any precipitate by filtration, the filtrate was partitioned between EtOAc/H2O (100/20 mL). The organic layer was washed with brine and dried over MgSO4. After removal of the solvent under vacuum, the residue was chromatographed on silica gel using 0%-20% gradient EtOAc/Hexanes to elute the title compound as a yellow brownish oil (150 mg, 27%) MS (ESI) 323 (M+H)+. After removal of any precipitate by filtration the filtrate was partitioned between EtOAc/H2O (100/20 mL) The organic layer was washed with brine dried over MgSO4 After removal of the solvent under vacuum the residue was chromatographed on silica gel using 0%-20% gradient EtOAc/Hexanes to elute the title compound as a yellow brownish oil (150 mg, 27%)

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

実験手順: Following preparation as described in Patent: WO2002/101146, 3-methoxy-4-(2-(pyrrolidin-1-yl)ethoxy)benzenamine (59 mg, 0.25 mol) was stirred overnight in DMF (2 mL) containing with 4-(4-chlorophenyl)-1H-pyrrole-2-carboxylic acid (65 mg, 0.25 mol), EDC (96 mg, 0.50 mol), HOBT (77 mg, 0.50 mol) and NaHCO3 (116 mg, 1.37 mol). After dilution of the reaction with 40 mL of EtOAc, the organic layer was washed with H2O (10 mL×2) and brine. The organic layer was dried over Na2SO4, and conc. in vacuum to a brown oil. The oil was purified by flash column chromatography (silica gel, CH3OH in CH2Cl2, 0-10% gradient) to yield 109 mg (99%) of the title compound as a colorless oil. MS (ESI) 440 (M+H)+. preparation the organic layer was washed with H2O (10 mL×2) and brine The organic layer was dried over Na2SO4 The oil was purified by flash column chromatography (silica gel, CH3OH in CH2Cl2, 0-10% gradient)

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

実験手順: 6-[(S)-1-(Tetrahydrofuran-2-yl)methoxy]isochroman-1-one was firstly converted with thionyl chloride by method B into the corresponding dichloride, and then reacted with 3-methoxy-4-(2-pyrrolidin-1-ylethoxy)phenylamine by method A. The product with the molecular weight of 466.58 (C27H34N2O5) was obtained in this way; MS (ESI): 467 (M+H+). The product with the molecular weight of 466.58 (C27H34N2O5) was obtained in this way

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

実験手順: 5-Chloro-2-nitrobenzoic acid [Aldrich] (600 mg, 3 mmol) was suspended in dichloromethane (5 ml) and treated with oxalyl chloride (2 ml) and DMF (1 drop). On stirring, an immediate effervescence occurred which ceased after 1 hour. The solvent was removed in vacuo and the residue dissolved in dichloromethane (10 ml) and treated successively with DIEA resin (3.1 mmol/g, 1.95 g) and 3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (650 mg, 3 mmol). The mixture was stirred at RT for 16 hours then filtered, evaporated, and the residue purified by flash chromatography (methanol-dichloromethane-aqueous ammonia) to afford 5-chloro-N-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-2-nitro-benzamide as a yellow foam; The solvent was removed in vacuo the residue dissolved in dichloromethane (10 ml) The mixture was stirred at RT for 16 hours then filtered evaporated the residue purified by flash chromatography (methanol-dichloromethane-aqueous ammonia)

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

実験手順: To a solution of 3-methoxy-4-[2-(1-pyrrolidinyl)ethoxy]aniline (43 mmol, 10.0 g) in DCM was added triethylamine (52 mmol, 5.2 g) and 4-chloro-2-nitrobenzoyl chloride (9.5 g, 43 mmol). The solution was stirred overnight. The reaction mixture was extracted with 2N HCl. The resulting acidic aqueous solution was made basic by adding 2N NaOH. The combined basic aqueous solution was extracted with DCM. The organic phase was washed with brine, dried and concentrated giving the title compound (11.5 g, 69%). 1H NMR (DMSO-D6): δ 1.66 (4H, m), 2.49 (4H, m), 2.75 (2H, t, J=6.0 Hz), 3.72 (3H, s), 4.00 (2H, t, J=6.0 Hz), 6.94 (1H, d, J=8.6 Hz), 7.14 (1H, d, J=8.6 Hz), 7.79 (1H, d, J=8.1 Hz), 7.94 (1H, d, J=8.1 Hz), 8.23 (1H, s), 10.55 (1H, s). LCMS m/z=420 (m+H+). The reaction mixture was extracted with 2N HCl by adding 2N NaOH The combined basic aqueous solution was extracted with DCM The organic phase was washed with brine dried concentrated