反应详情

To a solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (500 mg, 1.987 mmol) (prepared as in Ex. 2, Part A) in DMF (6 mL) cooled to 0° C. was added EDC (571 mg, 2.98 mmol) and HOBT (609 mg, 3.97 mmol) and the mixture was stirred for 5 min. To the resultant solution DIPEA (1.04 mL, 5.96 mmol) followed by cyclopropanamine (567 mg, 9.93 mmol) was added and the mixture was stirred at room temperature for 12 h. The reaction mixture was treated with ice and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (1×10 mL), dried (Na2SO4) and concentrated under reduced pressure to afford 4-(4-chloro-2-fluorophenyl)-N-cyclopropylnicotinamide (480 mg, 1.65 mmol, 83% yield). LC/MS (ESI) m/e 291.0 [(M+H)+, calcd for C15H13ClFN2O 291.1]; LC/MS retention time (method C): tR=1.79 min.

1. additionwas added
2. stirringthe mixture was stirred at room temperature for 12 h
3. additionThe reaction mixture was treated with ice
4. extractionextracted with ethyl acetate (3×10 mL)
5. washThe combined organic layers were washed with brine (1×10 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated under reduced pressure