反应详情

温度

160 °C

Combine 2-chloro-N-[4-chloro-6-[[(1R)-2-hydroxy-1-methyl-ethyl]amino]-2-methyl-pyrimidin-5-yl]benzamide (13.0 g), IPA (11 mL), of N-methylpiperizine (7.1 mL) and diisopropylethylamine (7.0 mL) in a 300 mL Parr autoclave with mechanical stirrer. Seal the reaction vessel and heat to 160° C. for 24 h. Evaporate all volatile materials, dissolve in dichloromethane (100 mL) to give a dark solution. Wash with water (2×50 mL), dry using a hydrophobic frit, and evaporate all the solvent under reduced pressure. Take the resulting solid and dissolve in acetonitrile (85 mL) and stir. After 1.5 h collect the solids by filtration and air dry, before dying under vacuum to provide the title compound (10.73 g). Determine optical purity by chiral SFC to show a single enantiomer. ES/MS m/z 401.2 (M+1). Chiral HPLC conditions: Diacel AD-H, 10% IPA, 0.2% isopropylamine, 89.8% supercritical carbon dioxide, UV (220 nm), TR=4.22 min, 100% ee.

1. customSeal the reaction vessel
2. customEvaporate all volatile materials
3. dissolutiondissolve in dichloromethane (100 mL)
4. customto give a dark solution
5. washWash with water (2×50 mL)
6. customdry
7. customevaporate all the solvent under reduced pressure
8. dissolutiondissolve in acetonitrile (85 mL)
9. customAfter 1.5 h collect the solids
10. filtrationby filtration and air
11. customdry