Diisopropylamine → Telaprevir, (alpha-ketoamide bond reduced)-

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Reaction Steps

The title compound is prepared from the hydroxy-amino amide product of Step g by condensation with the appropriate acid in the presence of a coupling reagent such as, e.g., EDCI and HOSu. Specifically, in a flask containing 1.2 eq. of (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid (1.59 g) in 20 mL of DMF, is added 2.5 eq. of diisopropylamine (980 uL), 1.2 eq. N-hydroxybenzotriazole hydrate (411 mg) and 1.3 eq. of EDCI (558 mg). After 15 minutes of stirring at the room temperature, 1.0 eq. of (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride (500 mg) is added to the mixture. After another 24 hours, the reaction mixture is diluted into 400 mL of ethyl acetate. The organic phase of the mixture is washed with HCl (1N), water, saturated sodium bicarbonate solution, brine, and then dried over MgSO4. The crude product is purified by chromatography on silica (ethyl acetate 70-100% in Hexanes) to give the tile compound.

Provenance & Evidence