Triethylamine → 2-[{[tert-butyl(methyl)amino]carbonyl}(3,5-difluorobenzyl)amino]-N-[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro[imidazolidine-4,2'-inden]-5'-yl]acetamide

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To a solution of N,2-dimethylpropan-2-amine (16.0 mg, 0.189 mmol) and triethylamine (19.1 mg, 0.189 mmol) in DCM (1.5 mL), cooled to 0° C., was added triphosgene (19.0 mg, 0.0640 mmol), followed by additional triethylamine (28.7 mg, 0.284 mmol). After 10 minutes of stirring at 0° C., the ice bath was removed and the reaction was allowed to warm to ambient temperature. After 45 minutes at ambient temperature the reaction was cooled to 0° C. prior to the introduction of a chilled (0° C.), DCM (1 mL) solution of triethylamine (19.1 mg, 0.189 mmol) and N-(3,5-difluorobenzyl)-2-{[(4S)-3-methyl-2,5-dioxo-1′,3′-dihydrospiro[imidazolidine-4,2′-inden]-5′-yl]amino}-2-oxoethanaminium chloride (85.0 mg, 0.189 mmol, Intermediate 1). The ice bath was allowed to slowly melt overnight as the reaction warmed to ambient temperature. The reaction was then diluted with EtOAc (50 mL) and then washed with 1M HCl (50 mL, twice), half-saturated brine (50 mL) and saturated brine (50 mL). After drying over sodium sulfate, filtration and concentration in vacuo gave a residue which was applied to a silica gel column for purification, eluting with DCM:MeOH—99:1 to 90:10. The product containing factions were pooled and concentrated in vacuo to give a residue that was not of sufficient purity. This residue was applied to a second silica gel column for purification, eluting with DCM:MeOH—99:1 to 95:5. The product containing factions were pooled and concentrated in vacuo to give 30 mg of the title compound. MS: m/z=550 (M+23(Na+)). HRMS: m/z=528.2428; calculated m/z=528.2417 for C27H32N5O4F2.

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