N-benzyl-2-chloroethanamine;hydrochloride

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

実験手順: To a chilled suspension of 39.5 g (0.823 mol) 50% sodium hydride in 500 mL dimethylformamide add 37.32 g (0.233 mol) 4-(1H imidazol-1-yl)phenol. When the addition is complete, stir the reaction mixture at room temperature until gas evolution ceases. After this time, chill the reaction mixture below 0° C. and slowly add 60.22 g (0.292 mol) N-benzyl(2-chloro)ethylamine hydrochloride. When the addition is complete, heat the reaction mixture to 65° C. Follow the progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol) (9:1). At the completion of the reaction, add 20 mL water to the cooled mixture. Filter the slats and remove the solvents in vacuo to obtain an oil. Column chromatograph the oil on silica gel using methylene chloride+methanol (1+99→1+19) as eluent. Collect the appropriate fractions and remove the solvents to obtain the title compound as the free base. Dissolve the free base in excess methanolic HCl solution and remove the solvent in vacuo to provide the title compound. When the addition When the addition heat the reaction mixture to 65° C the progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol) (9:1) At the completion of the reaction Filter the slats remove the solvents in vacuo to obtain an oil Collect the appropriate fractions remove the solvents

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Combine N-(3-aminophenyl)acetamide (31 g, 0.206 mol) and N-(2-chloroethyl)benzenemethanamine hydrochloride (17.0 g, 0.083 mol) and heat to 180° C. for 1 h. After this time, allow to cool to approximately 85° C. and add isopropanol (100 mL) to precipitate a solid. Decant the solvent and dissolve the white residue in refluxing methanol (800 mL). Filter hot and allow the solution to cool to room temperature. After 2 h, filter the resulting white solid and wash with methanol (50 mL) to give the title compound. to precipitate a solid Decant the solvent dissolve the white residue in refluxing methanol (800 mL) Filter hot to cool to room temperature filter the resulting white solid wash with methanol (50 mL)

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

実験手順: Combine 3-methoxybenzenamine (81.2 g, 0.66 mol) with N-(2-chloroethyl)-benzenemethanamine hydrochloride (45.3 g, 0.22 mol) and heat to 190° C. for 13 h. Add methylene chloride to precipitate a solid. Filter the solid and wash with methylene chloride. Triturate the solid with 100 mL of ethanol, filter the solid and wash with ethanol to give the title compound. Add methylene chloride to precipitate a solid Filter the solid wash with methylene chloride Triturate the solid with 100 mL of ethanol filter the solid wash with ethanol

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

実験手順: To a suspension of 39.5 g (0.82 mol) sodium hydride in 500 mL DMF add 37.3 g (0.233 mol) 4-(1H-imidazol-yl)phenol portionwise. Chill the reaction mixture on an ice/MeOH bath during the addition. After addition, stir the reaction mixture at room temperature until gas evolution ceases. After this time, return the reaction mixture to the ice bath and add 50.2 g (0.29 g) N-benzyl-2-chloroethylamine hydrochloride portionwise. After addition is complete, heat the stirring suspension to 65° C. Followthe progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol, 9:1). At the completion of the reaction, cool to room temperature and slowly add 20 mL H2O. Remove the solidsby suction filtration and evaporate the solvents. Chromatograph the resulting oil on silica gel using (CH2Cl2 :MeOH, 98:2), to isolate the title compound as the free base. Dissolve the free base in excess 3 M methanolic HCl and evaporate the solvents to give the title compound. Chill the reaction mixture on an ice/MeOH bath during the addition After addition After addition heat the stirring suspension to 65° C progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol, 9:1) At the completion of the reaction cool to room temperature Remove the solidsby suction filtration evaporate the solvents

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

実験手順: To a suspension of 39.5 g (0.82 mol) sodium hydride in 500 mL DMF add 37.3 g (0.233 mol) 4-(1H-imidazol-yl)phenol portionwise. Chill the reaction mixture on an ice/MeOH bath during the addition. After addition, stir the reaction mixture at room temperature until gas evolution ceases. After this time, return the reaction mixture to the ice bath and add 50.2 g (0.29 g) N-benzyl-2-chloroethylamine hydrochloride portionwise. After addition is complete, heat the stirring suspension to 65° C. Followthe progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol, 9:1). At the completion of the reaction, cool to room temperature and slowly add 20 mL H2O. Remove the solidsby suction filtration and evaporate the solvents. Chromatograph the resulting oil on silica gel using (CH2Cl2 :MeOH, 98:2), to isolate the title compound as the free base. Dissolve the free base in excess 3 M methanolic HCl and evaporate the solvents to give the title compound. Chill the reaction mixture on an ice/MeOH bath during the addition After addition After addition heat the stirring suspension to 65° C progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol, 9:1) At the completion of the reaction cool to room temperature Remove the solidsby suction filtration evaporate the solvents

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

実験手順: A solution of 13 (8.618 g, 42.0 mmol) and aniline (11.75 g, 126 mmol) in toluene (40 niL) was heated to 130° C. (1.5 h). The mixture was triturated with dichloromethane (200 mL) and filtered. Recrystallization from ethanol (220 mL) afforded the title compound 14 as white crystals. The mixture was triturated with dichloromethane (200 mL) filtered Recrystallization from ethanol (220 mL)

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

実験手順: A solution of N-benzyl-2-aminoethanol (12, 79.05 g, 0.523 mole) in chloroform (400 niL) was treated with thionyl chloride (80 mL, 1.09 mole) at room temperature. The resulting mixture was heated to reflux (6 h). The solvent was removed in vacuo, the residue dissloved in hot ethanol (1.3 L) and cooled overnight. The solids were collected via suction filtration and dried in vacuo at 65° C. (24 h) to afford the title compound 13 as white plates. The resulting mixture was heated to reflux (6 h) The solvent was removed in vacuo cooled overnight The solids were collected via suction filtration dried in vacuo at 65° C. (24 h)

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

実験手順: A solution of N-benzyl-2-aminoethanol (12, 79.05 g, 0.523 mole) in chloroform (400 niL) was treated with thionyl chloride (80 mL, 1.09 mole) at room temperature. The resulting mixture was heated to reflux (6 h). The solvent was removed in vacuo, the residue dissloved in hot ethanol (1.3 L) and cooled overnight. The solids were collected via suction filtration and dried in vacuo at 65° C. (24 h) to afford the title compound 13 as white plates. The resulting mixture was heated to reflux (6 h) The solvent was removed in vacuo cooled overnight The solids were collected via suction filtration dried in vacuo at 65° C. (24 h)

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

実験手順: To a chilled suspension of 39.5 g (0.823 mol) 50% sodium hydride in 500 mL dimethylformamide add 37.32 g (0.233 mol) 4-(1H imidazol-1-yl)phenol. When the addition is complete, stir the reaction mixture at room temperature until gas evolution ceases. After this time, chill the reaction mixture below 0° C. and slowly add 60.22 g (0.292 mol) N-benzyl(2-chloro)ethylamine hydrochloride. When the addition is complete, heat the reaction mixture to 65° C. Follow the progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol) (9:1). At the completion of the reaction, add 20 mL water to the cooled mixture. Filter the slats and remove the solvents in vacuo to obtain an oil. Column chromatograph the oil on silica gel using methylene chloride+methanol (1+99→1+19) as eluent. Collect the appropriate fractions and remove the solvents to obtain the title compound as the free base. Dissolve the free base in excess methanolic HCl solution and remove the solvent in vacuo to provide the title compound. When the addition When the addition heat the reaction mixture to 65° C the progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol) (9:1) At the completion of the reaction Filter the slats remove the solvents in vacuo to obtain an oil Collect the appropriate fractions remove the solvents

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

実験手順: 2-Benzylaminoethanol (18.8 ml, 20 g, 0.13 mol) was converted to N-(2-chloroethyl)-N-benzylamine hydrochloride with thionyl chloride (19 ml, 31 g, 0.26 mol) according to the procedure described in J. Chem. Soc. 1955, 896. N-(2-chloroethyl)-N-benzylamine hydrochloride (4.0 g, 19 mmol) was converted to N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride by the procedure of Syn. Comm. 18, 45-50 (1988), using o-toluidine (6.1 ml, 6.1 g, 57 mmol) in place of aniline. 1-benzyl-4-(2-methylphenyl)piperazine-2-carboxamide was prepared from 2,3-dibromopropionamide (7.9 g, 34 mmol) by the procedure of J. Med. Chem. 35, 743-750 (1992) using N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride (4.95 g, 18 mmol) in place of N-benzyl-N'-phenyl-1,2-diaminoethane hydrochloride.

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

実験手順: 2-Benzylaminoethanol (18.8 ml, 20 g, 0.13 mol) was converted to N-(2-chloroethyl)-N-benzylamine hydrochloride with thionyl chloride (19 ml, 31 g, 0.26 mol) according to the procedure described in J. Chem. Soc. 1955, 896. N-(2-chloroethyl)-N-benzylamine hydrochloride (4.0 g, 19 mmol) was converted to N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride by the procedure of Syn. Comm. 18, 45-50 (1988), using o-toluidine (6.1 ml, 6.1 g, 57 mmol) in place of aniline. 1-benzyl-4-(2-methylphenyl)piperazine-2-carboxamide was prepared from 2,3-dibromopropionamide (7.9 g, 34 mmol) by the procedure of J. Med. Chem. 35, 743-750 (1992) using N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride (4.95 g, 18 mmol) in place of N-benzyl-N'-phenyl-1,2-diaminoethane hydrochloride.

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

実験手順: A solution of 2 (8.618 g, 42.0 mmol) and aniline (11.75 g, 126 mmol) in toluene (40 mL) was heated to 130° C. (1.5 h). The mixture was triturated with dichloromethane (200 mL) and filtered. Recrystallization from ethanol (220 mL) afforded the title compound 3 as white crystals. The mixture was triturated with dichloromethane (200 mL) filtered Recrystallization from ethanol (220 mL)