反应详情

To a mixture of 1-(pyridazin-3-yl)cyclopropanecarboxylic acid (160 mg, 0.97 mmol), O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′,-tetramethyluronium hexafluorophosphate (HATU) (445 mg, 1.17 mmol) and diisopropylethyl amine (330 mg, 2.4 mmol) in anhydrous dichloromethane (10 mL) was added (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (350 mg, 0.98 mmol) dissolved in anhydrous dichloromethane (10 mL) with diisopropylethyl amine (330 mg, 2.4 mmol). The reaction mixture was stirred at room temperature for 2 h, diluted with dichloromethane and washed with water. The organics were dried over sodium sulfate and concentrated under reduced pressure. The resulting crude was purified via column chromatography (100-200 silica gel mesh, 60-80% ethyl acetate in petroleum ether) to afford (R)—N-(2-amino-6-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1-(pyridazin-3-yl)cyclopropanecarboxamide (100 mg, 23%). MS (ES+APCI) (M+H) 436.2; LCMS retention time: 3.390 min (Method W1).

1. washwashed with water
2. dry with materialThe organics were dried over sodium sulfate
3. concentrationconcentrated under reduced pressure
4. customThe resulting crude was purified via column chromatography (100-200 silica gel mesh, 60-80% ethyl acetate in petroleum ether)