反应详情

To a solution of 5,6-diamino-3-(4-methoxybenzyl)-1-methylpyrimidine-2,4(1H,3H)-dione (80 mg, 0.289 mmol, intermediate 59) in ethanol (2 mL) was added 2-(2-fluoro-5-(trifluoromethoxy)phenyl)acetic acid (68.8 mg, 0.289 mmol) followed by EDCI (66.5 mg, 0.347 mmol) and the mixture was stirred at room temperature for 2 h. The reaction was partitioned between ethyl acetate and brine. The organic phase was dried and concentrated. The residue was dissolved in ethanol (3 mL) and 1 mM sodium hydroxide (1 mL) was added. The resulting mixture was stirred at reflux for 3 h. The reaction was concentrated and residue was partitioned between ethyl acetate and brine. The organic layer was dried and concentrated to give a crude solid product, which was triturated with ethanol, collected and dried to afford 8-(2-fluoro-5-(trifluoromethoxy)benzyl)-1-(4-methoxybenzyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (67 mg, 48.4% yield) as a light yellow solid. LCMS retention time 1.611 min; LCMS MH+ 479.

1. customThe reaction was partitioned between ethyl acetate and brine
2. customThe organic phase was dried
3. concentrationconcentrated
4. dissolutionThe residue was dissolved in ethanol (3 mL)
5. addition1 mM sodium hydroxide (1 mL) was added
6. stirringThe resulting mixture was stirred
7. temperatureat reflux for 3 h
8. concentrationThe reaction was concentrated
9. customresidue was partitioned between ethyl acetate and brine
10. customThe organic layer was dried
11. concentrationconcentrated
12. customto give a crude solid product, which
13. customwas triturated with ethanol
14. customcollected
15. customdried