Trifluoroacetic acid → N-(2-(2-(2-(4-(1-((E)-3-(6-Bromopyridin-2-yl)-2-cyanoacrylamido)butyl)phenoxy)ethoxy)ethoxy)ethyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide

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Reaction Steps

A mixture of (E)-(2-(2-(2-(4-(1-(3-(6-bromopyridin-2-yl)-2-cyanoacrylamido)butyl)phenoxy)ethoxy)ethoxy)ethyl)imidodicarbonic acid, 1,3-bis-tert-butyl ester (47; 105 mg, 0.14 mmol) and trifluoroacetic acid (0.3 mL) was stirred in dichloromethane (3 mL) for 1.5 hours. The solution was concentrated and the residue was dissolved in N,N-dimethylformamide. To this solution at ice bath temperature was added D-biotin N-hydroxysuccinimide ester (49 mg, 0.14 mmol) and DIPEA (75 μL, 0.43 mmol). The resulting mixture was stirred at this temperature for 2 hours and then partitioned between dichloromethane and water. The organic phase was washed with water (2×) and sat. brine, dried over sodium sulfate, and concentrated to afford an oil. Purification by flash silica gel column chromatography, eluting with 7:93 methanol/dichloromethane, provided 48 (55 mg, 51%) as a pale yellow oil: (MS (ES+) m/z 757.2 (M+H)+.

Provenance & Evidence