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Synthesis

I. Preparation of Compound 613: tert-Butyl (1R,3S,4S)-3-(6-bromo-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (264 mg, 0.673 mmol), bis(pinacol) 1,4-phenylene diboronate (5 eq, 3.36 g, 6.95 mmol), tetrakis(triphenylphosphine) A mixture of palladium (5%, 39 mg) and 2M aqueous potassium carbonate (3 eq, 1.01 mL) in 5 mL of 1,2-dimethoxyethane (DME) was heated to 90°C for 4 hours under argon protection. After completion of the reaction, the reaction mixture was cooled, diluted with ethyl acetate and washed with saturated sodium bicarbonate solution. The organic layer was dried over anhydrous magnesium sulfate, concentrated, and purified by fast column chromatography (silica gel, 20% to 60% ethyl acetate/hexane gradient elution) to afford (1R,3S,4S)-3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1] Heptane-2-carboxylic acid tert-butyl ester (295 mg, 85% yield).LCMS-ESI (m/z): [M+H]+ Calculated value C30H38BN3O4: 515.45; Measured value: 516.1.

References

[1] Patent: WO2013/40492, 2013, A2. Location in patent: Page/Page column 91-92
[2] Patent: US2013/273005, 2013, A1. Location in patent: Paragraph 0350