反应详情

To a cold (0° C.) solution of [5-bromo-2-(methylthio)pyrimidin-4-yl]methanol (Step 13, 2.20 g, 9.34 mmol) in CH2Cl2 (46.7 mL) was added triphenylphosphine (3.19 g, 12.14 mmol) followed by carbon tetrabromide (4.03 g, 12.14 mmol). The resulting mixture was stirred cold for 1 h. LCMS trace of the aliquot indicated completion of reaction. Volatiles were removed under reduced pressure. Half of the crude material was purified by flash chromatography (SiO2, Biotage 40M cartridge). The column was eluted with an isocratic acetone/hexanes mixture (2.5%, v/v). No purification was obtained. All fractions and reaction crude were combined and purified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (51% to 62% organic in 10 min, hold 62% for 2 min, 20 mL/min). Related fractions were combined and evaporated under reduced pressure. The desired compound azeotroped with the water and was extracted with EtOAc, washed with brine, dried (Na2SO4), filtered and concentrated to afford a light brown oil as the titled compound. LCMS calc.=297.86; found=298.87.

1. customcompletion of reaction
2. customVolatiles were removed under reduced pressure
3. customHalf of the crude material was purified by flash chromatography (SiO2, Biotage 40M cartridge)
4. washThe column was eluted with an isocratic acetone/hexanes mixture (2.5%, v/v)
5. customNo purification
6. customwas obtained
7. customAll fractions and reaction crude
8. custompurified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
9. washeluting with MeCN/water+0.1% TFA (51% to 62% organic in 10 min, hold 62% for 2 min, 20 mL/min)
10. customevaporated under reduced pressure
11. customThe desired compound azeotroped with the water
12. extractionwas extracted with EtOAc
13. washwashed with brine
14. dry with materialdried (Na2SO4)
15. filtrationfiltered
16. concentrationconcentrated