Acetone → HCID 23643984, compound

Participants

Reaction Steps

To a solution of 1-[5-fluoro-4-methoxy-2-(trifluoromethyl)quinolin-8-yl]piperidin-4-one (Step 4, 0.31 g, 0.9 mmol, 1 eq.) and 6-methoxy-8-(1-piperazinyl)quinoline (Example A, Step 4, 0.30 g, 1.23 mmol, 1.37 eq.) in anhydrous methanol (20 mL) was added sodium cyanoborohydride (0.103 g, 1.64 mmol, 1.82 eq.). The resulting mixture was stirred overnight at room temperature under nitrogen (app. 18 hr). An additional aliquot of sodium cyanoborohydride (0.10 g, 1.59 mmol, 1.76 eq.) was added and stirring at room temperature was continued overnight. The resulting reaction mixture was poured into brine and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to a yellow oil. The desired product was isolated by chromatography on a 40 g silica column (1000 mL 20% acetone in hexane followed by 500 mL 30% acetone in hexane) as a yellow solid (0.113 g, 22% yield). The free base was converted to its trihydrochloride sesquihydrate salt by dissolving it in dichloromethane (3 mL), adding diethyl ether (9 mL), cooling in an ice bath and adding 1M HCl/Et2O (1 mL). The resulting yellow solid was collected by vacuum filtration, washed with ether and dried in vacuo to give 0.152 g. MS (ES) m/z (relative intensity): 570 (M+H)+ (100).

Provenance & Evidence