反应详情

温度

80 °C

Combine 2-chlorobenzoyl chloride (10.44 g, 57.86 mmol), 5-amino-4,6-dichloro-2-methylpyrimidine (10 g, 56.17 mmol) and N-methylpyrrolidone (44 mL) in a 250 mL three-necked round bottom flask equipped with reflux condenser, stirrer bar, and nitrogen inlet/outlet and heat to 80° C. for 5 h. Add water (506 μL) and continue stirring under the heating conditions for 20 min before adding diisopropylethylamine (29.4 mL, 168.52 mmol). Then add (R)-(−)-2-amino-1-propanol (6.23 mL, 79.77 mmol) in one portion followed by a rinse with N-methylpyrrolidone (10 mL). Continue heating at 80° C. for 17 h. Allow the reaction solution to cool to room temperature and then add water (112 mL) dropwise via an addition funnel over 10 min. Continue stirring at room temperature for 35 min and then pour into ethyl acetate (300 mL). Separate the phases and extract the aqueous with ethyl acetate (2×200 mL). Wash the combined organic portions with water (200 mL) and then brine (200 mL), dry over magnesium sulfate, filter, and evaporate to afford an orange oil. Triturate this with tert-butyl methyl ether to afford a white solid, after collection by filtration. Dry the solids on the filter for 0.5 h and then in a vacuum oven at 50° C. to afford the title compound (15.1 g). ES/MS m/z 355.0/357.0 (M+1).

1. temperaturewith reflux condenser, stirrer bar, and nitrogen inlet/outlet
2. washa rinse with N-methylpyrrolidone (10 mL)
3. temperatureContinue heating at 80° C. for 17 h
4. temperatureto cool to room temperature
5. additionpour into ethyl acetate (300 mL)
6. customSeparate the phases
7. extractionextract the aqueous with ethyl acetate (2×200 mL)
8. washWash the combined organic portions with water (200 mL)
9. dry with materialbrine (200 mL), dry over magnesium sulfate
10. filtrationfilter
11. customevaporate
12. customto afford an orange oil
13. customTriturate this with tert-butyl methyl ether
14. customto afford a white solid
15. customafter collection
16. filtrationby filtration
17. customDry the solids on the
18. filtrationfilter for 0.5 h