反应详情

A 250 mL flask fitted with a condenser was charged with (R)-6-benzyl-N-(1-(4-chlorophenyl)ethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine (4.43 g, 11.7 mmol), 1,2-dichloroethane (50 mL), α-chloroethyl chloroformate (1.5 mL, 14 mmol) and finally N,N-diisopropylethylamine (2.4 mL, 14 mmol), and the resultant red-brown solution was placed in an oil bath at 60° C. Additional α-chloroethyl chloroformate (2.0 mL, 18.4 mmol, 1.6 eq) was added after 2.5 h. After 4 h the mixture was concentrated to a brown oil and the residue was dissolved in methanol (50 mL), and heated at reflux for 1 h. After cooling, the mixture was concentrated in vacuo, and the residue was partitioned between 4/1 ethyl acetate/CH2Cl2 (100 mL) and 0.5M aq. NaH2PO4 (100 mL). The organic layer was extracted with 1M citric acid (2×25 mL), and the combined aqueous layers were basified to pH>12 with 50% aqueous KOH (50 mL), and extracted with CH2Cl2 (250 mL, 50 mL). The combined CH2Cl2 extracts were dried (Na2SO4) and concentrated to give an orange solid foam (4.0 g), which was purified by basic alumina column (0-5% MeOH/CH2Cl2) to give a light yellow foam (1.48 g).

1. customA 250 mL flask fitted with a condenser
2. customthe resultant red-brown solution was placed in an oil bath at 60° C
3. concentrationAfter 4 h the mixture was concentrated to a brown oil
4. dissolutionthe residue was dissolved in methanol (50 mL)
5. temperatureheated
6. temperatureat reflux for 1 h
7. temperatureAfter cooling
8. concentrationthe mixture was concentrated in vacuo
9. customthe residue was partitioned between 4/1 ethyl acetate/CH2Cl2 (100 mL) and 0.5M aq. NaH2PO4 (100 mL)
10. extractionThe organic layer was extracted with 1M citric acid (2×25 mL)
11. extractionextracted with CH2Cl2 (250 mL, 50 mL)
12. dry with materialThe combined CH2Cl2 extracts were dried (Na2SO4)
13. concentrationconcentrated