2-(dimethylamino)ethanesulfonic acid

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[8-(cis-3,5-Dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (101.7 mg, 0.21 mmol) were added to a tetrahydrofuran solution (5.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (33.8 mg, 0.21 mmol) at room temperature and the resulting mixture was stirred for 1 day. 1H-Benzotriazole-1-carboxyaldehyde (5.1 mg, 0.03 mmol) was added, the resulting mixture was further stirred for 1 day, and then the reaction mixture was poured into methylene chloride and washed with a 2 N aqueous sodium hydroxide solution. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (98.0 mg, 91%) as a pale yellow solid. the resulting mixture was further stirred for 1 day washed with a 2 N aqueous sodium hydroxide solution The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{8-[(3R)-3-Methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine (101.9 mg, 0.21 mmol) was added to a tetrahydrofuran solution (5.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (34.8 mg, 0.21 mmol) at room temperature and the resulting mixture was stirred for 105 minutes. The reaction mixture was poured into a 2 N aqueous sodium hydroxide solution and the resulting mixture was extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (96.8 mg, 90%) as a pale yellow solid. the resulting mixture was extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{8-[(3S)-3-Methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine (107.1 mg, 0.22 mmol) was added to a tetrahydrofuran solution (5.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (36.6 mg, 0.22 mmol) at room temperature and the resulting mixture was stirred for 45 minutes. The reaction mixture was poured into a 2 N aqueous sodium hydroxide solution and the resulting mixture was extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (100.2 mg, 88%) as a pale yellow solid. the resulting mixture was extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{9-Isobutyl-8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (123.4 mg, 0.27 mmol) was added to a tetrahydrofuran solution (7.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (44.6 mg, 0.27 mmol) at room temperature and the resulting mixture was stirred for 35 minutes. Methylene chloride was added to the reaction mixture and then the resulting mixture was poured into a 2 N aqueous sodium hydroxide solution and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (98.3 mg, 75%) as a pale yellow solid. extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{9-Isobutyl-8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (109.5 mg, 0.24 mmol) was added to a tetrahydrofuran solution (7.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (39.6 mg, 0.24 mmol) at room temperature and the resulting mixture was stirred for 70 minutes. Methylene chloride was added to the reaction mixture and the resulting mixture was poured into a 2 N aqueous sodium hydroxide solution and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (107.9 mg, 93%) as a pale yellow solid. extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[9-(Isobutyl)-6-morpholin-4-yl-8-piperazin-1-yl-9H-purin-2-yl]pyrimidin-2-amine (129.8 mg, 0.30 mmol) was added to a tetrahydrofuran solution (7.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (48.4 mg, 0.30 mmol) at room temperature and the resulting mixture was stirred for 75 minutes. Methylene chloride was added to the reaction mixture and the resulting mixture was poured into 2 N aqueous sodium hydroxide solution and extracted with methylene chloride-methanol (10:1). The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by medium pressure silica gel column chromatography (methylene chloride:methanol=49:1 to 32:1) to give the title compound (103.4 mg, 75%) as a pale yellow solid. extracted with methylene chloride-methanol (10:1) The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by medium pressure silica gel column chromatography (methylene chloride:methanol=49:1 to 32:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-[8-(cis-3,5-Dimethylpiperazin-1-yl)-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl]pyrimidin-2-amine (101.7 mg, 0.21 mmol) were added to a tetrahydrofuran solution (5.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (33.8 mg, 0.21 mmol) at room temperature and the resulting mixture was stirred for 1 day. 1H-Benzotriazole-1-carboxyaldehyde (5.1 mg, 0.03 mmol) was added, the resulting mixture was further stirred for 1 day, and then the reaction mixture was poured into methylene chloride and washed with a 2 N aqueous sodium hydroxide solution. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (98.0 mg, 91%) as a pale yellow solid. the resulting mixture was further stirred for 1 day washed with a 2 N aqueous sodium hydroxide solution The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{8-[(3R)-3-Methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine (101.9 mg, 0.21 mmol) was added to a tetrahydrofuran solution (5.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (34.8 mg, 0.21 mmol) at room temperature and the resulting mixture was stirred for 105 minutes. The reaction mixture was poured into a 2 N aqueous sodium hydroxide solution and the resulting mixture was extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (96.8 mg, 90%) as a pale yellow solid. the resulting mixture was extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{8-[(3S)-3-Methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine (107.1 mg, 0.22 mmol) was added to a tetrahydrofuran solution (5.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (36.6 mg, 0.22 mmol) at room temperature and the resulting mixture was stirred for 45 minutes. The reaction mixture was poured into a 2 N aqueous sodium hydroxide solution and the resulting mixture was extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (100.2 mg, 88%) as a pale yellow solid. the resulting mixture was extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{8-[(3S)-3-Methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine (107.1 mg, 0.22 mmol) was added to a tetrahydrofuran solution (5.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (36.6 mg, 0.22 mmol) at room temperature and the resulting mixture was stirred for 45 minutes. The reaction mixture was poured into a 2 N aqueous sodium hydroxide solution and the resulting mixture was extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (100.2 mg, 88%) as a pale yellow solid. the resulting mixture was extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{9-Isobutyl-8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (123.4 mg, 0.27 mmol) was added to a tetrahydrofuran solution (7.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (44.6 mg, 0.27 mmol) at room temperature and the resulting mixture was stirred for 35 minutes. Methylene chloride was added to the reaction mixture and then the resulting mixture was poured into a 2 N aqueous sodium hydroxide solution and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (98.3 mg, 75%) as a pale yellow solid. extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 5-{9-Isobutyl-8-[(3S)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9H-purin-2-yl}pyrimidin-2-amine (123.4 mg, 0.27 mmol) was added to a tetrahydrofuran solution (7.0 ml) of 1H-benzotriazole-1-carboxyaldehyde (44.6 mg, 0.27 mmol) at room temperature and the resulting mixture was stirred for 35 minutes. Methylene chloride was added to the reaction mixture and then the resulting mixture was poured into a 2 N aqueous sodium hydroxide solution and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the mixture was filtrated, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (98.3 mg, 75%) as a pale yellow solid. extracted with methylene chloride The organic layer was dried over anhydrous sodium sulfate the mixture was filtrated the filtrate was concentrated under reduced pressure the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1)