Hydrochloric Acid → 5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylbenzonitrile

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Reaction Steps

Magnesium turnings (37.3 mg, 1.53 mmol) were stirred under Ar(g) for 10 min and LiCl 0.5M in THF (1.841 mL, 0.92 mmol) was added followed by DIBAL-H 1M in THF (6.14 μL, 6.14 μmol). The mixture was stirred for 5 min and 5-bromo-2-methoxy-3-methylbenzonitrile (194 mg, 0.86 mmol) in THF (1 mL) was added in one portion and stirring was continued for 2 h. The solution was transferred via canula to N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (250 mg, 0.61 mmol) in THF (3 mL) at rt and stirred o.n. MeOH (4 mL) was added and the mixture was treated with HCl in MeOH (1.473 mL, 1.84 mmol) o.n. The solvents were removed in vacuo, and the residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel chromatography using a gradient of 0 to 2.5% (3.5 M ammonia in methanol) in dichloromethane afforded 0.088 g (32% yield) of the title compound.

Provenance & Evidence