反应详情

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.

1. additionare added
2. customthe layers are separated
3. washthe organic phase is washed with saline
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customto give a solid which
7. customis chromatographed on silica gel (70-230 mesh, 46 g)
8. washeluting with a gradient of methanol/chloroform (2.5/97.5-6/94)
9. customby TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure
10. customgives an impure solid
11. customPurification of this solid on two 2000 μ preparative silica gel plates
12. washeluting with methanol/chloroform (10/90)
13. extractionextracting the appropriate band