Water → 1-((1-methyl-1H-indol-4-yl)methyl)-9-(quinoxalin-2-yl)-1,9-diazaspiro[5.5]undecan-2-one

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Reaction Steps

The title compound was synthesized from 1-((1H-indol-4-yl)methyl)-9-(quinoxalin-2-yl)-1,9-diazaspiro[5.5]undecan-2-one (prepared according to method G) via methylation as follows: NaH (7 mg, 0.18 mmol, 60% in mineral oil) was added to an ice-cold solution of 1-((1H-indol-4-yl)methyl)-9-(quinoxalin-2-yl)-1,9-diazaspiro[5.5]undecan-2-one (synthesized according to method G) (25 mg, 0.06 mmol) in THF (5 mL). The resulting mixture was stirred at rt for 10 min. The mixture was cooled to 0° C., methyl iodide (26 mg, 0.18 mmol) was added at 0° C. and stirring was continued at 0° C. for 1 h. Then the mixture was allowed to warm to rt over a period of 1 h. The mixture was poured into water and the solution was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, filtered and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure. The product was purified by preparative reversed phase HPLC (column Zorbax eclipseXDB C18 21.2×150 mm 5 ♀m, flow 20 mL/min, eluent: gradient water/acetonitrile) to yield the title compound (13 mg, 50%). [1H NMR (300 MHz, CDCl3) ♀ ppm 8.49 (s, 1H), 7.88 (d, 1H), 7.68-7.50 (m, 2H), 7.45-7.35 (m, 1H), 7.21-7.08 (m, 2H), 6.95 (d, 1H), 6.73 (d, 1H), 6.35 (d, 1H), 4.98 (s, 2H), 4.40 (d, 2H), 3.78 (s, 3H), 3.15 (t, 2H), 2.68 (t, 2H), 2.25-2.05 (m, 4H), 2.00-1.85 (m, 2H), 1.80-1.70 (m, 2H); LCMS RtF=1.50 min, [M+H]+=440.0].

Provenance & Evidence