反应详情

To a cold (−10° C.˜0° C.) THF (19.00 mL) solution of methyl 5-bromo-2-(methylthio)pyrimidine-4-carboxylate (Step A, 1 g, 3.80 mmol) was added diisobutylaluminum hydride (1M, 9.50 mL, 9.50 mmol) while internal temperature was below 0° C. An aliquot taken immediately after addition indicated completion of reaction. The crude mixture was quenched with NH4Cl (aq.). Volatiles were removed under reduced pressure. The resulting pot residue was worked up with brine, extracted with EtOAc, dried (Na2SO4), filtered and evaporated to afford a dark mixture. The dark residue was purified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (10% to 80% organic in 10 min, then to 100% in 2 min). Related fractions were pooled and evaporated in vacuo to afford an aqueous mixture. The resulting mixture was extracted with EtOAc and washed with aqueous NaHCO3, dried (Na2SO4), filtered and concentrated to afford a brown oil. After further drying under reduced pressure, this oil solidified to a crystalline solid. LCMS calc.=235.94; found=236.88.

1. customwas below 0° C
2. additionafter addition
3. customcompletion of reaction
4. customThe crude mixture was quenched with NH4Cl (aq.)
5. customVolatiles were removed under reduced pressure
6. extractionextracted with EtOAc
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. customevaporated
10. customto afford a dark mixture
11. customThe dark residue was purified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
12. washeluting with MeCN/water+0.1% TFA (10% to 80% organic in 10 min
13. customevaporated in vacuo
14. customto afford an aqueous mixture
15. extractionThe resulting mixture was extracted with EtOAc
16. washwashed with aqueous NaHCO3
17. dry with materialdried (Na2SO4)
18. filtrationfiltered
19. concentrationconcentrated
20. customto afford a brown oil
21. customAfter further drying under reduced pressure