Sodium hydride → 1-[4-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-1-(tetrahydropyran-4-yl)-cyclohexyl]propylamine

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Reaction Steps

To a suspension of sodium hydride (60%, 167 mg, 4.17 mmol, 3 eq.) in dimethyl acetamide (8 mL) was added a solution of 4-(1-aminopropyl)-4-(tetrahydropyran-4-yl)-cyclohexanol (7,369 mg, 1.53 mmol, 1.1 eq.) in dimethyl acetamide (8 mL). After stirring for 60 min at room temperature a solution of 1-benzyloxy-7-chloro-6-fluoro-isoquinoline (1,400 mg, 1.39 mmol) in dimethyl acetamide (8 mL) was added and stirring was continued first at room temperature, then at 50° C. until the reaction went to completion. The reaction was quenched by addition of water (30 mL) and the reaction mixture was extracted three times with a mixture of dichloromethane and 2-propanol (3:1). The combined organic layers were evaporated, and the obtained crude product was purified by flash chromatography (SiO2, 0%→30% methanol in dichloromethane) to yield 83 mg (earlier eluting isomer 1, 8) and 48 mg (later eluting isomer 2, 9) of the pure diastereoisomers as racemates respectively. The relative stereochemistry was not assigned. Additionally, 166 mg of the product as a diastereomeric mixture could be isolated. Rt=0.92 min (8), 0.93 min (9) (Method B). Detected mass: 419.4 (M+H+).

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