Quinolinemethanol Derivatives as Purine Receptor Antagonists

Patent 4-Quinolinemethanol Derivatives as Purine Receptor Antagonists 

Utility Treatment of Neurodegenerative Disorders or Movement Disorders 

A solution of 2,8-bis(trifluoromethyl)-4-bromoquinoline (1.45 mmol) dissolved in 10 ml diethyl ether at —78°C was added to 0.64 ml 2.5 M n-butyl lithium followed by 0.15 ml benzaldehyde and the mixture stirred 1 hour. The mixture was quenched with 10 ml water, slowly warmed to ambient temperature, and extracted 3 times with 20 ml diethyl ether. The combined extracts were dried, concentrated, purified by chromatography on silica gel using heptane/EtOAc, 3 1, and the product isolated in 36% yield as a pale-yellow solid, mp = 151-152°C. H-NMR, IR, and elemental data supplied. 

A solution of l-(2,8-bis(trifluoromethyl)-4-quinolinyl)-4-hydroxyl-butanone (2.13 mmol) dissolved in 4 ml ethyl aleohol at 0°C was treated with a solution of NaBH4 (2.13 mmol) in 0.2 ml water, stirred 30 minutes, poured into 15 ml water, extracted twice with 10 ml EtOAc, dried, and concentrated. The material was purified by chromatography on silica gel with EtOAc/heptane, 2 1, and the product isolated in 82% yield as a colorless oil. H-NMR, IR, and elemental data supplied. 

A solution of methyl 2-hydroxy-4-quinolinecarboxylate (2 mmol) dissolved in 20 ml THE at 0°C was treated with a solution of 2.3 ml 1.8 M phenyl lithium (4.2 mmol), stirred at ambient temperature 2 hours, then poured into 100 ml water. The precipitate was filtered, dried, and the product isolated in 97% yield as a cream colored solid, mp 350°C. H-NMR, IR, MS, and elemental data supplied. 

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