Diisopropylethylamine → 2-{4-(2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(propylamino)pyridin-4-yl)phenoxy}ethyl N2,N6-bis(tert-butoxycarbonyl)-L-lysyl-L-alaninate

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Reaction Steps

445 mg (1.284 mmol) of N2,N6-bis(tert-butoxycarbonyl)-L-lysine were initially charged in 12.3 ml of DMF. 268 mg (1.400 mmol) of 1-hydroxy-1H-benzotriazole hydrate, 237 mg (1.750 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.51 ml (2.917 mmol) of N,N-diisopropylethylamine were added, and 872 mg (1.167 mmol) of 2-{4-(2-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-3,5-dicyano-6-(propylamino)pyridin-4-yl)phenoxy}ethyl L-alaninate trifluoroacetate (Example 38) were then added and the mixture was stirred at RT overnight. Water was added, and the reaction solution was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated by evaporation. The residue was purified by preparative HPLC (acetonitrile/water+0.1% TFA). For further purification, the product obtained was subjected to column chromatography on silica gel 60 (mobile phase: cyclohexane/ethyl acetate 1/1). This gave 698 mg (62% of theory) of the target compound.

Provenance & Evidence