Acetone → 4-Methyl-3-[1-oxo-7-(2-piperidin-1-ylethoxy)isoquinolin-2(1H)-yl]benzoic acid

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Reaction Steps

3-(7-hydroxy-1-oxoisoquinolin-2(1H)-yl)-4-methylbenzoic acid (885 mg) was dissolved in acetone (50 ml), Sodium iodide (45 mg) and potassium carbonate (4.14 g) were added followed by 4-(2-chloroethyl)piperidine hydrochloride (1.67 g). The resultant mixture was stirred at 60° C. for 18 hours. 2N NaOH (9.4 ml) was added and stirred for 20 minutes, cooled and the insoluble material removed by filtration. The filtrate was concentrated, acidified to pH 1 with concentrated hydrochloric acid and purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution to give 4-methyl-3-[7-(2-piperidin-1-ylethoxy)-1-oxoisoquinolin-2(1H)-yl]benzoic acid as an oil (205 mg); NMR Spectrum: (DMSOd6) 2.13 (s, 1H), 3.00 (m, 4H), 3.35 (m, 2H), 3.95 (m, 4H), 4.58 (m, 2H), 6.46 (d, 1H), 6.90 (d, 1H), 7.25 (m, 1H), 7.35 (m, 1H), 7.50 (d, 1H), 7.80 (d, 1H), 7.87 (d, 1H), 7.98 (m, 1H); Mass Spectrum: M+H+ 407.

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