To a suspension of sodium hydride (60% in mineral oil, 72 mg, 1.80 mmol) in N,N-dimethylformamide (1 mL) was added 5-cyanooxindole (213 mg, 1.35 mmol), and the mixture was stirred at ambient temperature for 15 min. To the obtained brownish solution was added a solution of 2-chloro-5-(pyrrolidin-1-ylmethyl)pyridine 1-oxide (191 mg, 0.90 mmol) in N,N-dimethylformamide (1.5 mL). The obtained red solution was heated at 125° C. for 20 min, and was then allowed to cool. The mixture was dissolved in 2 M HCl(aq) and washed with ethyl acetate. The organic layer was extracted with 2 M HCl(aq). The combined aqueous layers were alkalized to saturation with NaHCO3 (s), and extracted two times with ethyl acetate. The extracts were combined, dried (Na2SO4) and the solvent was removed in vacuo to give 270 mg of a crude product. The material was dissolved in ethyl acetate (15 mL), and a solution of phosphorus trichloride (0.25 mL, 2.87 mmol) in ethyl is acetate (3 mL) was added. An orange precipitate was immediately formed. The mixture was heated at reflux for 30 min, and was then allowed to cool. The mixture was partitioned between ethyl acetate and a saturated aqueous NaHCO3 solution. The aqueous layer was extracted with another two portions of ethyl acetate. The combined organic layers were dried (Na2SO4) and the solvent was evaporated to give a crude product which was purified on a silica gel column using chloroform/methanol/conc. NH3(aq), (90:10:0.5), as the eluent affording 85 mg (37% yield) of the title compound as the free base as an orange solid: 1H NMR (CDCl3, 400 MHz) δ 14.9 (br s, 1 H), 9.02 (s, 1 H), 7.78 (dd, J=9, 2 Hz, 1 H), 7.68 (s, 1 H), 7.60 (s, 1 H), 7.46 (d, J=9 Hz, 1 H), 7.25-7.22 (m, 1 H), 7.05 (d, J=8 Hz, 1 H), 3.56 (s, 2 H), 2.55-2.51 (m, 4 H), 1.83-1.79 (m, 4 H); MS (ES) m/z 319 (M++1). The base (65 mg) was dissolved in a mixture of ethyl acetate (20 mL), methylene chloride (10 mL), and methanol (2 mL), and was then cooled on an ice-bath. A solution of HCl in diethyl ether (1 M) was added until acidic pH. About 60% of the solvent volume was evaporated and to the residual suspension was added ethyl acetate. The obtained orange hydrochloride was filtered, washed with ethyl acetate, and dried in vacuo at 40° C. affording 65 mg (95% yield from the base) of the title compound as a brownish solid: 1H NMR (DMSO-d6, 400 Mz) δ 14.70 (br s, 1 H), 11.00 (br s, 1 H), 10.97 (s, 1 H), 8.31 (s, 1 H), 8.07 (dd, J=9, 1 Hz, 1 H), 8.02 (s, 1 H), 7.91 (d, J=8 Hz, 1 H), 7.32 (d, J=7 Hz, 1 H), 7.02 (d, J=7 Hz, 1 H), 4.29 (d, J=6 Hz, 2 H), 3.45-3.39 (m, 2 H), 3.09-3.02 (m, 2 H), 2.04-1.98 (m, 2 H), 1.92-1.87 (m, 2 H).
