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A solution of 4-bromo-2-fluoro-N-methoxy-N-methyl-benzamide (CAS [801303-33-3]) (13.1 g, 50.0 mmol) in THF (50 mL) at −78 C was treated with a 3 M solution of methyl magnesium bromide in diethyl ether (16.7 mL, 50 mmol) and allowed to warm with stirring to 0 C over a 2-3 h period, after which time the reaction mixture was quenched with a half saturated aqueous solution of NH4Cl (100 mL) and EtOAc (200 mL). The mixture was separated and the organic component, washed with brine (2×50 mL), dried over MgSO4, filtered, and evaporated to an oil which was purified by silica gel flash chromatography with 5% EtOAc/hexanes as eluant to afford 1-(4-bromo-2-fluorophenyl)-ethanone as a liquid (9.25 g, 85%). The ethanone (2.17 g, 10 mmol) was then dissolved in ethanol (25 mL), treated with hydrazine hydrate (535 uL, 11 mmol), and heated at reflux for 8 h. The reaction mixture was then evaporated and purified by silica gel flash chromatography with 30% then 60% EtOAc/hexanes as eluant to afford the hydrazone as a solid (2.29 g, 99%). The hydrazone (3.69 g, 16 mmol) was then treated with ethylene glycol (25 mL) and heated at 165° C. for 6 h after which time the cooled reaction mixture was poured onto water (100 mL). The aqueous mixture was neutralized, with rapid stirring, using a small amount of an aqueous saturated solution of NaHCO3 to afford a pale yellow precipitate. The solids were filtered, washed with water, and air dried to afford cyclized indazole product (2.62 g, 78%). The indazole (2.32 g, 11 mmol) was then dissolved in anhydrous DMF (50 mL) and treated with a 60% dispersion of sodium hydride in mineral oil (420 mg, 10.5 mmol). After 30 min of stirring, cyclopentyl bromide (1.53 mL, 14.3 mmol) was added and the reaction stirred for 24 h. The reaction mixture was quenched by pouring onto water (500 mL) which was neutralized with a small portion of a 1 N aqueous HCl solution and extracted with EtOAc (2×200 mL, then 100 mL). The combined organic extracts were dried over MgSO4, filtered, and evaporated to an oil, which was purified by silica gel flash chromatography with 25% then 80% EtOAc/hexanes as eluant to afford product as a clear yellow tinted oil (1.65 g, 54%). 1H NMR (CDCl3) 1.68-1.78 (m, 2H), 1.93-2.01 (m, 2H), 2.08-2.16 (m, 4H), 2.54 (s, 3H), 4.77-4.87 (m, 1H), 7.18 (dd, J=8.4, 1.5, 1H), 7.32 (dd, J=8.4, 0.7, 1H), 7.55 (d, J=1.5, 1H). 13C NMR 12.1 (CH3), 24.7 (CH2), 32.2 (CH2), 59.5 (CH), 112.2 (CH), 120.5, 121.8 (CH), 122.5, 123.2 (CH), 141.1, 141.4. LC/MS 7.71 min, [M+1]+ 281.

1. temperatureto warm
2. customafter which time the reaction mixture was quenched with a half saturated aqueous solution of NH4Cl (100 mL) and EtOAc (200 mL)
3. customThe mixture was separated
4. washthe organic component, washed with brine (2×50 mL)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customevaporated to an oil which
8. customwas purified by silica gel flash chromatography with 5% EtOAc/hexanes as eluant