反应详情

温度

20 °C

A mixture of 5-(4-chloro-phenyl)-7-cyclopropyl-3-iodo-pyrazolo[1,5-a]pyrimidine (example C.5, step 4) (1.58 g, 4.0 mmol), trimethylsilylacetylene (0.78 mL, 6.0 mmol), and Et3N (12.0 mL, 45 mmol) in N,N-dimethylformamide (12 mL) was stirred for 10 min at 20° C. while being purged with Argon. Then, PdCl2(PPh3)2 (56 mg, 2 mol %), PPh3 (42 mg, 4 mol %) and CuI (15 mg, 4 mol %) were added and stirring was continued at 75° C. for 15 h in an atmosphere of argon. The mixture was cooled to 20° C. and partitioned between EtOAc and water. The organic layer was dried (Na2SO4) and evaporated in vacuo. The residue (2.2 g) was dissolved in a mixture of THF (8 mL) and MeOH (20 mL), potassium carbonate (0.11 g, 0.8 mmol) was added, and the solution was stirred for 2 h at 0° C. followed by 1 h at 20° C. The mixture was partitioned between EtOAc and 10% sodium chloride solution. The organic layer was dried (Na2SO4) and evaporated in vacuo. The residue was chromatographed on silica gel using EtOAc/cyclohexane (1:5 v/v) as eluent and crystallization from EtOAc/cyclohexane gave 5-(4-chloro-phenyl)-7-cyclopropyl-3-ethynyl-pyrazolo[1,5-a]pyrimidine (0.47 g, 40%) as a yellow solid; mp 181-182° C.

1. customwhile being purged with Argon
2. additionThen, PdCl2(PPh3)2 (56 mg, 2 mol %), PPh3 (42 mg, 4 mol %) and CuI (15 mg, 4 mol %) were added
3. stirringstirring
4. waitwas continued at 75° C. for 15 h in an atmosphere of argon
5. temperatureThe mixture was cooled to 20° C.
6. custompartitioned between EtOAc and water
7. dry with materialThe organic layer was dried (Na2SO4)
8. customevaporated in vacuo
9. additionwas added
10. stirringthe solution was stirred for 2 h at 0° C.
11. waitfollowed by 1 h at 20° C
12. customThe mixture was partitioned between EtOAc and 10% sodium chloride solution
13. dry with materialThe organic layer was dried (Na2SO4)
14. customevaporated in vacuo
15. customThe residue was chromatographed on silica gel
16. customcrystallization from EtOAc/cyclohexane