Reaktion #79785

Reaktionsgleichung

8-tosyloxy-1,4-dioxaspiro[4,5]decane

Sodium hydride

5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine

1,4-dioxaspiro[4,5]decan-8-one

hydrogen

→

5-(4-phenoxyphenyl)-7-(1,4-dioxaspiro[4,5]decan-8-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine

Lösungsmittel

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   Temperaturcooled to ambient temperature
3. 3
   Sonstigequenched with water
4. 4
   Extraktionextracted with ethyl acetate
5. 5
   Sonstigeto give a residue which
6. 6
   Sonstigewas purified by flash column chromatography on silica
7. 7
   Temperaturincreasing amounts of methanol up to 6%

Vorschrift

Sodium hydride (0.26 g of a 60% dispersion in mineral oil) was added to a mixture of 5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine (1.94 g) in dimethylformamide 950 ml) at ambient temperature with stirring. The mixture was stirred until the evolution of hydrogen ceased and then 8-tosyloxy-1,4-dioxaspiro[4,5]decane (2.0 g, prepared as described in U.S. Pat. No. 4,360,531 from 1,4-dioxaspiro[4,5]decan-8-one, (which was prepared according to J. Med. Chem. 1992, 22460) was added. The mixture was heated at 120° C. for 5 hours under nitrogen, cooled to ambient temperature, quenched with water and extracted with ethyl acetate to give a residue which was purified by flash column chromatography on silica using ethyl acetate followed by ethyl acetate containing increasing amounts of methanol up to 6% to give 5-(4-phenoxyphenyl)-7-(1,4-dioxaspiro[4,5]decan-8-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine, m.p. 193-194° C.

Quelle