4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → 1-[5-((S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-pyrrolidin-2-yl)-pyridin-3-yl]-1H-indole-3-carboxylic acid ethyl ester

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Reaction Steps

To a solution of 1-((S)-5-pyrrolidin-2-yl-pyridin-3-yl)-1H-indole-3-carboxylic acid ethyl ester (I-2A-2b: 0.25 g, 0.75 mmol) and (S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3-methylbutanoic acid (0.26 g, 0.86 mmol, prepared from (S)-2-amino-3-methyl-butyric acid methyl ester and (S)-2-(tert-butoxycarbonyl-methyl-amino)-propionic acid via amide coupling followed ester hydrolysis) in THF (41 mL) at 0° C. was added 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) (0.25 g, 0.89 mmol). The mixture was warmed to room temperature, stirred for 3 hours, then quenched with water (20 mL) and concentrated under reduced pressure to remove THF. The remaining mixture was extracted with EtOAc (3×40 mL) and the organic layers were combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure to give an oil. This oil was purified by silica gel column chromatography using 90-100% EtOAc/heptane to give the titled compound as a white solid (0.30 g, 65%).

Provenance & Evidence