Sodium hydride → 3-{6-[2-(2-Methoxyethoxy)ethoxy]isoquinolin-1-yl}-2-oxo-2,3-dihydro-1H-indole-5-carbonitrile Trifluoroacetate

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Reaction Steps

A suspension of sodium hydride (92 mg, 3.55 mmol, 95% powder) in tetrahydrofuran (10 mL) was slowly added via a cannula to a solution of 2-oxo-5-indolinecarbonitrile (292 mg, 1.85 mmol) in tetrahydrofuran/N-methylpyrrolidinone (15 mL, 2:1) under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 25 min. A solution of chloro-6-[2-(2-methoxyethoxy)ethoxy]isoquinoline (400 mg, 1.42 mmol) in tetrahydrofuran (10 mL) was added and the reaction solution was stirred at room temperature over night. The reaction was quenched by slow addition of hydrochloric acid (1 M) and concentrated in vacuo to a slurry. The slurry was diluted with acetonitrile (5 mL) and purified by prep RP-HPLC (C18 2″ column, gradient:acetonitril/water, 20:80→0:100+0.1% TFA). The appropriate fractions were pooled and lyophilized giving 193 mg (27% yield) of the title compound as an orange trifluoroacetate salt. MS (AP+) m/z 404 (M+1).

Provenance & Evidence