Tetrahydrofuran → HCID 178526691, compound

To 150 ml of a tetrahydrofuran suspension containing 10 g of trans-4-aminocyclohexanol was added 15 ml of triethylamine, 50 ml of a tetrahydrofuran solution containing 2-chloro-5-nitropyridine was further added thereto under ice-cooling, and then, the mixture was stirred at room temperature for 18 hours. Water was added to the reaction mixture and the mixture was extracted with chloroform. The extract was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel flash column chromatography (solvent: ethyl acetate-hexane (2:1)) to obtain 8.52 g of trans-4-(5-nitro-2-pyridylamino)cyclohexanol. (2) To 10 ml of a dichloromethane solution containing 1.0 g of the compound obtained in the above (1) was added 1.8 ml of triethylamine, 0.65 ml of methanesulfonyl chloride was further added thereto under ice-cooling, and the mixture was stirred for 1 hour. An aqueous saturated sodium bicarbonate solution was added to the reaction mixture and the mixture was extracted with chloroform. The extract was washed with water and brine, dried over anhydrous sodium sulfate, and then, the solvent was removed under reduced pressure. 1.37 g of sodium azide was added to a solution of the residue dissolved in 10 ml of dimethylformamide and the mixture was stirred at 50° C. for 3 days. After cooling, an aqueous saturated sodium bicarbonate solution was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with water and brine, dried over sodium sulfate, and then, the solvent was removed under reduced pressure. The residue was purified by silica gel flash column chromatography (solvent: ethyl acetate-hexane (1:5)) to obtain 758 mg of cis-4-azide-N-(5-nitro-2-pyridyl)cyclohexylamine. (3) A solution comprising 10 ml of tetrahydrofuran-1 ml of water, containing 640 mg of the compound obtained in the above (2) and 704 mg of triphenylphosphine was stirred at room temperature for 2 days. The reaction mixture was concentrated, and the residue was purified by silica gel flash column chromatography (solvent: ethyl acetatemethanol (10:1)) to obtain 531 mg of N-(5-nitro-2-pyridyl)-cis-1,4-cyclohexanediamine (the compound of Reference Example 4 in Table 5).

1. additionwas further added
2. temperatureunder ice-cooling
3. extractionthe mixture was extracted with chloroform
4. washThe extract was washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. customthe solvent was removed under reduced pressure
7. customThe residue was purified by silica gel flash column chromatography (solvent: ethyl acetate-hexane (2:1))

ORD record

ord-1bffefb8759b4146a4e8e6c8963e3fdd

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07160877B2