1,4-Dioxane hydrochloride → (S)-2-(6-(1-amino-2-(3,5-difluorophenyl)ethyl)-5-bromopyridin-3-yl)isoindoline-1,3-dione hydrochloride

Participants

Reaction Conditions

Reaction Steps

(S)—N—((S)-1-(3-bromo-5-(1,3-dioxoisoindolin-2-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (30D, 2.6 G, 4.6 mmol) was dissolved in 40 mL of methanol and cooled to 0° C. To it was added 4N HCl/1,4-dioxane (4.6 ml). The reaction mixture was allowed to stir at room temperature for 10 minutes and concentrated to afford product (S)-2-(6-(1-amino-2-(3,5-difluorophenyl)ethyl)-5-bromopyridin-3-yl)isoindoline-1,3-dione hydrochloride. To the mixture of the above HCl salt (˜4.6 mmol) and di-tert-butyl dicarbonate (1 g, 4.6 mmol) in 50 mL of CH2Cl2 was added triethylamine (1.28 mL, 9.2 mmol) at 0° C. The reaction mixture was stirred for overnight and concentrated in vacuo. The residue was partitioned between EtOAc and H2O. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Then it was purified on silica gel chromatography eluting with EtOAc/hexanes to yield the title compound. MS (m/z) 559.71 [M+H]+.

Provenance & Evidence