2-(dimethylamino)ethanesulfonyl chloride;hydrochloride

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

実験手順: To a solution of 1-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino]piperidine (VII, PREPARATION 56, 400 mg) in dry methylene chloride (5 ml) under nitrogen at 0° is added triethylamine (275 μl) and 2-(dimethylamino)ethanesulfonyl chloride hydrochloride (225 mg). The mixture is stirred at 0° for 1 hr and at 20°-25° for 23 during which additional sulfonyl chloride (20 mg) and triethylamine (14 μl) are added. The mixture is then diluted with 4 ml of water, the layers are separated, and the organic phase is washed with saline, dried over sodium sulfate and concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g), eluting with a gradient of methanol/chloroform (2.5/97.5-6/94). Pooling of fractions having an Rf of 0.36 by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid. Purification of this solid on two 2000 μ preparative silica gel plates, eluting with methanol/chloroform (10/90) and extracting the appropriate band, gives the title compound, NMR (CDCl3) 10.17, 7.71, 7.55, 7.35, 7.11, 6.94, 6.84, 6.69, 4.63, 4.50, 3.56, 3.45, 3.18, 3.30-3.00, 2.84, 2.63, 2.25, 1.93, 1.65 and 1.22 δ. are added the layers are separated the organic phase is washed with saline dried over sodium sulfate concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g) eluting with a gradient of methanol/chloroform (2.5/97.5-6/94) by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid Purification of this solid on two 2000 μ preparative silica gel plates eluting with methanol/chloroform (10/90) extracting the appropriate band

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

実験手順: To a solution of 1-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino]piperidine (VII, PREPARATION 56, 400 mg) in dry methylene chloride (5 ml) under nitrogen at 0° is added triethylamine (275 μl) and 2-(dimethylamino)ethanesulfonyl chloride hydrochloride (225 mg). The mixture is stirred at 0° for 1 hr and at 20°-25° for 23 during which additional sulfonyl chloride (20 mg) and triethylamine (14 μl) are added. The mixture is then diluted with 4 ml of water, the layers are separated, and the organic phase is washed with saline, dried over sodium sulfate and concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g), eluting with a gradient of methanol/chloroform (2.5/97.5-6/94). Pooling of fractions having an Rf of 0.36 by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid. Purification of this solid on two 2000 μ preparative silica gel plates, eluting with methanol/chloroform (10/90) and extracting the appropriate band, gives the title compound, NMR (CDCl3) 10.17, 7.71, 7.55, 7.35, 7.11, 6.94, 6.84, 6.69, 4.63, 4.50, 3.56, 3.45, 3.18, 3.30-3.00, 2.84, 2.63, 2.25, 1.93, 1.65 and 1.22 δ. are added the layers are separated the organic phase is washed with saline dried over sodium sulfate concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g) eluting with a gradient of methanol/chloroform (2.5/97.5-6/94) by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid Purification of this solid on two 2000 μ preparative silica gel plates eluting with methanol/chloroform (10/90) extracting the appropriate band

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

実験手順: To a solution of 1-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino]piperidine (VII, PREPARATION 56, 400 mg) in dry methylene chloride (5 ml) under nitrogen at 0° is added triethylamine (275 μl) and 2-(dimethylamino)ethanesulfonyl chloride hydrochloride (225 mg). The mixture is stirred at 0° for 1 hr and at 20°-25° for 23 during which additional sulfonyl chloride (20 mg) and triethylamine (14 μl) are added. The mixture is then diluted with 4 ml of water, the layers are separated, and the organic phase is washed with saline, dried over sodium sulfate and concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g), eluting with a gradient of methanol/chloroform (2.5/97.5-6/94). Pooling of fractions having an Rf of 0.36 by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid. Purification of this solid on two 2000 μ preparative silica gel plates, eluting with methanol/chloroform (10/90) and extracting the appropriate band, gives the title compound, NMR (CDCl3) 10.17, 7.71, 7.55, 7.35, 7.11, 6.94, 6.84, 6.69, 4.63, 4.50, 3.56, 3.45, 3.18, 3.30-3.00, 2.84, 2.63, 2.25, 1.93, 1.65 and 1.22 δ. are added the layers are separated the organic phase is washed with saline dried over sodium sulfate concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g) eluting with a gradient of methanol/chloroform (2.5/97.5-6/94) by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid Purification of this solid on two 2000 μ preparative silica gel plates eluting with methanol/chloroform (10/90) extracting the appropriate band

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

実験手順: To a solution of 1-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino]piperidine (VII, PREPARATION 56, 400 mg) in dry methylene chloride (5 ml) under nitrogen at 0° is added triethylamine (275 μl) and 2-(dimethylamino)ethanesulfonyl chloride hydrochloride (225 mg). The mixture is stirred at 0° for 1 hr and at 20°-250° for 23 hrs, during which additional sulfonyl chloride (20 mg) and triethylamine (14 μl) are added. The mixture is then diluted with 4 ml of water, the layers are separated, and the organic phase is washed with saline, dried over sodium sulfate and concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g), eluting with a gradient of methanol/chloroform (2.5/97.5-6/94). Pooling of fractions having an Rf of 0.36 by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid. Purification of this solid on two 2000 μ preparative silica gel plates, eluting with methanol/chloroform (10/90) and extracting the appropriate band, gives the title compound, NMR (CDCl3) 10.17, 7.71, 7.55, 7.35, 7.11, 6.94, 6.84, 6.69, 4.63, 4.50, 3.56, 3.45, 3.18, 3.30-3.00, 2.84, 2.63, 2.25, 1.93, 1.65 and 1.22 δ. are added the layers are separated the organic phase is washed with saline dried over sodium sulfate concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g) eluting with a gradient of methanol/chloroform (2.5/97.5-6/94) by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid Purification of this solid on two 2000 μ preparative silica gel plates eluting with methanol/chloroform (10/90) extracting the appropriate band