反应详情

温度

60 °C

To a stiffed solution of (5-bromo-2-chloro pyrimidin-4-yl)-cyclopentyl-amine (1.00 g, 3.62 mmol) and PdCl2(dppf).dichloromethane (148 mg, 0.181 mmol) in THF (10 mL) is added Et3N (0.757 mL, 5.43 mmol) and 3,3-diethoxy-propyne (0.778 mL, 5.43 mmol) sequentially at room temperature. The mixture is degassed under a stream of N2 and stirred at room temperature for 10 minutes before CuI (29 mg, 0.154 mmol) is added. The reaction vessel is evacuated and back-filled with N2 (×3) and heated at 60° C. for 48 hours. The mixture is allowed to cool, diluted with EtOAc, filtered and partitioned between H2O and ethyl acetate. The phases are separated and the aqueous layer is further extracted with EtOAc (×3), combined organic extracts are dried (MgSO4), filtered and concentrated. The residue is purified by SiO2 chromatography, eluting with a gradient of 5% EtOAc/petrol to 20% EtOAc/petrol to give [2-chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]-cyclopentyl amine (636 mg, 54%). MS (ESI) m/z 324.2 (M+H)+

1. customThe mixture is degassed under a stream of N2
2. additionis added
3. customThe reaction vessel is evacuated
4. additionback-filled with N2 (×3)
5. temperatureto cool
6. additiondiluted with EtOAc
7. filtrationfiltered
8. custompartitioned between H2O and ethyl acetate
9. customThe phases are separated
10. extractionthe aqueous layer is further extracted with EtOAc (×3)
11. dry with materialare dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customThe residue is purified by SiO2 chromatography
15. washeluting with a gradient of 5% EtOAc/petrol to 20% EtOAc/petrol