反应详情

温度

100 °C

Ethyl 1-[5-[7-bromo-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylate (700 mg, 1.14 mmol), PdCl2(PPh3)2 (32 mg, 0.05 mmol) and triphenylphosphine (3 mg, 0.01 mmol) were placed in a 10-20 mL microwave vial and anhydrous DMF (14 mL) added, quickly followed by triethylamine (0.95 mL, 6.81 mmol) and propargyl alcohol (0.13 mL, 2.27 mmol). The solution was bubbled with argon for ˜3 minutes then CuI (4 mg, 0.02 mmol) was added. The vial was capped and mixture degassed then heated in the microwave at 100° C. for 30 minutes. More PdCl2(PPh3)2 (11 mg) and propargyl alcohol (0.05 mL) were added and argon was bubbled through the mixture then CuI (1.5 mg) added. The vial was capped and mixture degassed then heated in the microwave again at 100° C. for 15 minutes. The crude reaction mixture was filtered through a PTFE filter. The filter was rinsed with EtOAc and then water. The filtrate was diluted with water, extracted into EtOAc (4×60 mL) and the combined organic layers washed with water (2×50 mL) and brine, dried over Na2SO4 and concentrated to dryness under reduced pressure to give a brown solid. The mixture was purified by chromatography, Biotage SP4, 40 g Si cartridge, 50-80% EtOAc in cyclohexane and the relevant fractions combined to give the desired product as an off-white solid, 247 mg (37%). MS: 592.13 [M+H]+.

1. customThe solution was bubbled with argon for ˜3 minutes
2. customThe vial was capped
3. custommixture degassed
4. additionMore PdCl2(PPh3)2 (11 mg) and propargyl alcohol (0.05 mL) were added
5. customargon was bubbled through the mixture
6. additionCuI (1.5 mg) added
7. customThe vial was capped
8. custommixture degassed
9. temperaturethen heated in the microwave again at 100° C. for 15 minutes
10. customThe crude reaction mixture
11. filtrationwas filtered through a PTFE
12. filtrationfilter
13. washThe filter was rinsed with EtOAc
14. additionThe filtrate was diluted with water
15. extractionextracted into EtOAc (4×60 mL)
16. washthe combined organic layers washed with water (2×50 mL) and brine
17. dry with materialdried over Na2SO4
18. concentrationconcentrated to dryness under reduced pressure
19. customto give a brown solid
20. customThe mixture was purified by chromatography, Biotage SP4, 40 g Si cartridge, 50-80% EtOAc in cyclohexane