Citric Acid → HCID 57537565, compound

Participants

Reaction Steps

68 mg (0.12 mmol) of 5-[4-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-nicotinic acid ethyl ester was dissolved in methanol and 100 μL of 50% w/v of potassium hydroxide in water was added. The resulting mixture was left at room temperature for 8 h. The mixture was adjusted to pH 3 by addition of 100 μL of concentrated aqueous hydrochloric acid and the solvent completely evaporated. The residue was dissolved in 50 mL of 50% v/v methanol in diethyl ether. The insoluble residue was filtered off and the filtrate evaporated. The resulting material was dissolved in 10 mL of 50% v/v acetonitrile in dichloromethane. 100 μL (0.57 mmol) of di-iso-propylethylamine was added, followed by 92 mg (0.24 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate. The resulting suspension was sonicated until a homogeneous solution was obtained. 0.5 mL (1 mmol) of a 2 M solution of dimethylamine in anhydrous THF was added and the resulting mixture left at ambient temperature for 24 h. The resulting solution was distributed between dichloromethane and 10% w/v aqueous citric acid solution. The organic phase was dried over sodium sulfate and evaporated to afford 24 mg (45 μmol, 37%) of 5-[4-chloro-3-(5-fluoro-2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-nicotinamide. 1H-NMR [500 MHz, d6-DMSO] δ: 8.75 (d, 1H), 8.71 (d, 1H), 8.27 (s, 1H), 7.89 (t, 1H), 7.42 (s, 1H), 7.27 (s, 1H), 7.09-7.03 (m, 2H), 6.86 (dd, 1H), 5.74 (s, 2H), 3.74 (s, 3H), 3.64 (t, 2H), 3.15 (s, 3H), 3.08 (s, 3H), 0.97 (t, 2H), −0.2 (s, 9H); MS [MH+] m/z: 555.2.

Provenance & Evidence