Reaktion #359655

Reaktionsgleichung

4-(6-amino-pyridin-3-yl)-azepane-1-carboxylic acid tert-butyl ester

6-bromo-8-cyclopentyl-2-methanesulfinyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one

Succinic anhydride

→

4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-azepane-1-carboxylic acid tert-butyl ester

Ausbeute 43.4%

Lösungsmittel

toluene

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe heat was removed
2. 2
   workup.ADDITIONwas added
3. 3
   TemperaturThis mixture was refluxed for 12 h under N2
4. 4
   TemperaturThe reaction mixture was cooled
5. 5
   Waschenthe organic layer was washed with water (100 mL total)
6. 6
   TrocknenThe organic layer was dried over magnesium sulfate
7. 7
   Sonstigethe solvents evaporated
8. 8
   Wascheneluted with a chloroform/2-propanol gradient

Vorschrift

A solution of 4-(6-amino-pyridin-3-yl)-azepane-1-carboxylic acid tert-butyl ester (614 mg, 2.10 mmol) in toluene (10 mL) was refluxed in a Dean-Stark apparatus for 3 h. The heat was removed and when the reflux subsided 6-bromo-8-cyclopentyl-2-methanesulfinyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (700 mg, 1.89 mmol) was added. This mixture was refluxed for 12 h under N2. Succinic anhydride (500 mg) was added and the reflux continued for 3 h. The reaction mixture was cooled and dissolved in ethyl acetate (100 ml) and the organic layer was washed with water (100 mL total). The organic layer was dried over magnesium sulfate and the solvents evaporated. The crude product was subjected to chromatography on silica gel and eluted with a chloroform/2-propanol gradient to give 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-azepane-1-carboxylic acid tert-butyl ester as a yellow powder (414 mg, 0.82 mmol). MS (APCI+) 500, 600 (M+1, 100).

Quelle