反应详情

A mixture of 270 mg of [1-(5-carbamoyl-4-{(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy}-2-thienyl)-1H-imidazo[4,5-c]pyridin-6-yl]methyl methanesulfonate and 130 mg of (4-methylpiperazin-2-yl)methanol (synthesized starting from commercially available 1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid in one step in analogy to the synthesis of (2S)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid described in patent application WO2005/026152) in 10 ml dichloromethane is stirred at room temperature for 16 hours. 505 mg triethylamine is added and the reaction mixture is stirred additional 24 h at room temperature. Water (20 ml) is added to the mixture. After separation of the organic layer, the aqueous layer is extracted with dichloromethane (2×20 ml). The combined organic layers are dried over MgSO4. After filtration the solvent is removed under reduced pressure. The resulting residue is purified by flash chromatography [silica gel, eluent: ethyl acetate/methanol/aqueous solution of ammonia, 20/4/1 (v/v/v) and subsequently by preparative HPLC (ammonium formate buffer/acetonitrile, elution gradient 65/35 to 15/85 (v/v)) to give the title product.

1. customsynthesized
2. stirringthe reaction mixture is stirred additional 24 h at room temperature
3. customAfter separation of the organic layer
4. extractionthe aqueous layer is extracted with dichloromethane (2×20 ml)
5. dry with materialThe combined organic layers are dried over MgSO4
6. filtrationAfter filtration the solvent
7. customis removed under reduced pressure
8. customThe resulting residue is purified by flash chromatography [silica gel, eluent
9. washethyl acetate/methanol/aqueous solution of ammonia, 20/4/1 (v/v/v) and subsequently by preparative HPLC (ammonium formate buffer/acetonitrile, elution gradient 65/35 to 15/85 (v/v))