反应详情

Sodium cyanoborohydride (242 mg, 3.85 mmol) and then acetic acid (220 μl, 3.84 mmol) were added to a solution of 1-(methylsulfonyl)-1H-indazol-5-amine (163 mg, 0.772 mmol) and 8-propyl-8-azabicyclo[3.2.1]octan-3-one (150 mg, 0.924 mmol) in methanol (3 ml), and the resulting mixture was stirred at room temperature for 4 days. A 1N-aqueous sodium hydroxide solution was added thereto, followed by extraction with ethyl acetate. The extract solution was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, and then distilled under reduced pressure to remove the solvent. The residue was purified successively by a silica gel column chromatography (chloroform/methanol=4/1), a preparative thin-layer chromatography (200×200×0.5 mm, 2 plates, eluent: chloroform/methanol=4/1) and partition by LC/MS (water containing 0.05% trifluoroacetic acid-acetonitrile containing 0.035% trifluoroacetic acid, 10%–100% gradient, the extraction of the organic layer with aqueous ammonia/ethyl acetate after the partition) to obtain 1-(methylsulfonyl)-N-(8-propyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazol-5-amine (8 mg, 3%).

1. extractionfollowed by extraction with ethyl acetate
2. washThe extract solution was washed with a saturated aqueous sodium chloride solution
3. dry with materialdried over sodium sulfate
4. distillationdistilled under reduced pressure
5. customto remove the solvent
6. customThe residue was purified successively by a silica gel column chromatography (chloroform/methanol=4/1)
7. customa preparative thin-layer chromatography (200×200×0.5 mm, 2 plates, eluent: chloroform/methanol=4/1) and partition by LC/MS (water containing 0.05% trifluoroacetic acid-acetonitrile containing 0.035% trifluoroacetic acid, 10%–100% gradient
8. extractionthe extraction of the organic layer with aqueous ammonia/ethyl acetate after the
9. custompartition)