Ethanol → (+/-)-3-(4-fluorophenyl)-2-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To ethyl 6-(4-fluorobenzylidene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (Preparation 16; 303 mg, 1.07 mmol) and 6-hydrazinyl-3,4-dihydroisoquinolin-1(2H)-one (240 mg, 1.3 mmol) (U.S. Pat. No. 6,432,974, Kelly et al., Aug. 13, 2002, intermediate 2) was added ethanol (8 mL) and 21% sodium ethoxide in ethanol (1.5 mL, 4 mmol) in a vial. The vial was flushed with argon and heated at 80° C. overnight with stirring. The reaction was quenched with 1M hydrogen chloride (8 mL) and diluted with water to give a precipitate. The precipitate was collected by vacuum filtration to give a yellow solid. The solid was dissolved in of dimethylformamide (3 mL) and purified by reverse phase chromatography with 45-75% acetonitrile/water to give (±)-3-(4-fluorophenyl)-2-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid as a 25/75 mixture of the cis/trans-diastereomers (290 mg, 0.68 mmol, 63% yield). ES-MS m/z 430 (M+H).

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