Hydrochloric Acid → HCID 86715891, compound

Participants

Reaction Steps

To a solution of N#R)-2-(5-bromo-2-fluoropyridin-3-yl)-1-((2-cyanopropan-2-yl)sulfonyl)propan-2-yl)-2-methylpropane-2-sulfinamide (1.63 g, 3.48 mmol) in methanol (25 mL) was added hydrogen chloride (4.0 M in 1,4-dioxane, 4.35 mL, 17.4 mmol) and stirred at room temperature for 40 min until the starting material was consumed. The mixture was concentrated, diluted with DCM, and neutralized with 10% aqueous Na2CO3 and 1 M NaOH. The organic phase was dried over Na2SO4, filtered, and concentrated to afford (R)-2-((2-amino-2-(5-bromo-2-fluoropyridin-3-yl)propyl)sulfonyl)-2-methylpropanenitrile as a pale yellow oil. The (R)-2-((2-amino-2-(5-bromo-2-fluoropyridin-3-yl)propyl)sulfonyl)-2-methylpropanenitrile was dissolved in 1,2-dichloroethane (100 mL) and trimethylaluminum (2 M in toluene, 2.78 mL, 5.57 mmol) was added dropwise. The resulting mixture was stirred at room temperature for 17 h. The mixture was cooled to 0° C. and hydrochloric acid (1 M, 17.40 mL, 17.40 mmol) was added dropwise via an addition funnel (slowly at first until the vigorous reaction subsided) and stirred at room temperature. The aqueous solution was extracted with DCM. The pH of the aqueous phase was adjusted to pH>10 with 10 M NaOH and extracted with DCM. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (eluted with 0-100% EtOAc/hexanes) gave (R)-5-amino-3-(5-bromo-2-fluoropyridin-3-yl)-3,6,6-trimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide (1.0 g, 2.8 mmol, 79% yield) as a light yellow solid. LC/MS (ESI) m/z=364 (M+H).

Provenance & Evidence