反应详情

To tert-butyl 5-chloropyrazolo[1,5-a]pyrimidin-7-yl(2-morpholinopropyl)carbamate (396 mg, 1 mmol), 5-chloro-2-fluoroaniline (145 uL, 1.2 mmol), and LiHMDS (2.2 mL, 2.2 mmol, 1M in THF) was added X-Phos (11 mg, 0.024 mmol) and tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.02 mmol). The mixture was sealed and irradiated at 65° C. for 60 min in the microwave. The reaction was quenched with 1N HCL (2 mL) and then neutralized with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate and washed with saturated sodium chloride solution. The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude residue was dissolved in dichloromethane (2 mL) and trifluoroacetic acid (2 mL). After stirring at room temperature for 1 hour, the solution was concentrated under a stream of nitrogen. The crude material was neutralized with saturated sodium bicarbonate solution then purified by silica gel chromatography (75% ethyl acetate/hexanes) to yield the product, N5-(5-chloro-2-fluorophenyl)-N7-(2-morpholinopropyl)pyrazolo[1,5-a]pyrimidine-5,7-diamine (84 mg, 21% yield). LCMS (M+1=405)

1. customThe mixture was sealed
2. customirradiated at 65° C. for 60 min in the microwave
3. customThe reaction was quenched with 1N HCL (2 mL)
4. extractionThe mixture was extracted with ethyl acetate
5. washwashed with saturated sodium chloride solution
6. customThe organic layer was collected
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. customevaporated to dryness
10. dissolutionThe crude residue was dissolved in dichloromethane (2 mL)
11. concentrationthe solution was concentrated under a stream of nitrogen
12. customthen purified by silica gel chromatography (75% ethyl acetate/hexanes)