HCID 178484071, compound → HCID 178484070, compound

Participants

Reaction Steps

Trans-5-carboxy-3-[4-(dimethylamino)cyclohexyl-carbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (243 mg) obtained in Example 78 is suspended in thionyl chloride (2.5 ml), and the mixture is stirred at room temperature for 10 minutes, then stirred at 50° C. for 10 minutes. The mixture is cooled to room temperature and stirred for one hour. The reaction solution is concentrated to dryness under reduced pressure. The resulting residue is suspended in tetrahydrofuran/chloroform (2:1, 15 ml), and thereto is added sodium borohydride (150 mg), and the mixture is stirred at room temperature overnight. To the reaction solution is poured 1N hydrochloric acid under ice-cooling, and the mixture is stirred for 0.5 hour. A saturated aqueous sodium hydrogen carbonate solution is further poured thereto, and the mixture is extracted with chloroform. The organic layer is washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated brine, dried over sodium sulfate, and the solvent is evaporated under reduced pressure. The resulting residue is purified by NH-silica gel column chromatography (eluent: chloroform, then chloroform/methanol=200/1) to give trans-3-[4-(dimethylamino) cyclohexylcarbonylamino]-5-hydroxymethyl-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (46 mg). This product is dissolved in chloroform (1 ml), and thereto is added 2N hydrogen chloride in methanol (0.1 ml), and the reaction solution is concentrated under reduced pressure. The resulting residue is suspended in ethyl acetate-methanol, and the precipitates are collected by filtration, and dried to give the title compound (45 mg).

Provenance & Evidence