反应详情

温度

85 °C

6-(3-fluorophenyl)-N-(piperidin-4-yl)nicotinamide (2.0 g, 5.37 mmol) and 2-(6-chloro-9H-purin-9-yl)butan-1-ol (1.58 g, 6.98 mmol) were placed in a flask along with 10 mL of butanol, 10 mL of water and 10 mL of triethylamine. The mixture was heated to 85° C. for 2 hours. The reaction mixture was partitioned between ethyl acetate and brine. The ethyl acetate was washed 3× with brine and then dried over MgSO4, filtered and concentrated. The residue was purified by chromatography (silica, 1.5% EtOH/EtOAc) to give the desired racemic product (Example 88, 1.34 g, 57%). The material was purified by chiral chromatography-SFC (50% iPrOH in CO2, AD-H 30×250 mm col) to give the two peaks (enantiomeric pair)

1. customThe reaction mixture was partitioned between ethyl acetate and brine
2. washThe ethyl acetate was washed 3× with brine
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by chromatography (silica, 1.5% EtOH/EtOAc)
7. customto give the desired racemic product (Example 88, 1.34 g, 57%)
8. customThe material was purified by chiral chromatography-SFC (50% iPrOH in CO2, AD-H 30×250 mm col)
9. customto give the two peaks (enantiomeric pair)