Sodium hydride → Cyclopropanesulfonic acid {2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-amide

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Reaction Conditions

Reaction Steps

To a suspension of 60% sodium hydride (165 mg, 4.1 mmol) in N,N-dimethylformamide (1.5 mL) was added cyclopropanesulfonamide (510 mg, 4.2 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (150 mg, 0.42 mmol) and 1,1′-carbonyldiimidazole (170 mg, 1.04 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. After stirring at 70° C. for 1 h, the above suspension of cyclopropanesulfonamide and sodium hydride in N,N-dimethylformamide was added and the mixture was allowed to stir at 25° C. for 1 h. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded cyclopropanesulfonic acid {2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-amide (38 mg, 20%) as a white solid: LC/MS m/e calcd for C24H28FN3O3S (M+H)+: 458.57, observed: 458.1.

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