Reaktion #643783

Reaktionsgleichung

NaH

1,3-O-Benzylideneglycerol

product

8-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-2-methane-sulfonyl-8H-pyrido[2,3-d]pyrimidin-7-one

→

product

8-(2,6-Difluorophenyl)-4-(4-fluoro-2-methylphenyl)-2-(2-hydroxy-1-hydroxymethylethoxy)-8H-pyrido[2,3-d]pyrimidin-7-one

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture stirred for 15 minutes at 23° C.
2. 2
   Temperaturcooled to −78°
3. 3
   Temperaturto slowly warm to 23°
4. 4
   SonstigeThe solvent was removed in vacuo
5. 5
   workup.DISSOLUTIONthe residue was dissolved in acetic acid (2 mL)
6. 6
   workup.ADDITIONH2O (0.5 mL) was added
7. 7
   TemperaturThe mixture was heated in an oil bath to 60° C. for three h
8. 8
   Sonstigethe solvents were removed in vacua
9. 9
   Sonstigeto give the crude product
10. 10
    Sonstigechromatographed twice on silica gel
11. 11
    Wascheneluted with 20-50% EtOAc/CH2Cl2

Vorschrift

1,3-O-Benzylideneglycerol (100 mg, 0.55 mmol) was dissolved in dry THF (5 mL) and stirred under Ar at 23° C. NaH (14 mg, 0.55 mmol) was added and the mixture stirred for 15 minutes at 23° C., and then cooled to −78°. The product of Example 48 (222 mg, 0.5 mmol) was added, and the mixture was allowed to slowly warm to 23°. The solvent was removed in vacuo, and the residue was dissolved in acetic acid (2 mL), and H2O (0.5 mL) was added. The mixture was heated in an oil bath to 60° C. for three h, and then the solvents were removed in vacua to give the crude product. The crude product was flash chromatographed twice on silica gel eluted with 20-50% EtOAc/CH2Cl2 to give the product as a white-amorphous solid. 104-107° C., LC MS m/z=458 (MH+) Retention time=1.88 min.

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