4-Methylmorpholine → N-(N-(N-(N-(valeroyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11beta,21-dihydroxy-3,20-dioxo-6alpha-methyl-17-propionyloxy-pregna-1,4-dien-21-yl] ester

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Reaction Steps

307 mg (0.35 mmol) of H-Ala-Ala-Pro-Val-O-MPP x TFA (Example 3), 36 μl (0.33 mmol) of valeric acid, 52 mg (0.35 mmol) of N-hydroxy-benzotriazole and 74 μl (0.66 mmol) of N-methylmorpholine are dissolved in 40 ml of dichloromethane, mixed with a solution of 84 mg (0.41 mmol) of dicyclohexylcarbodiimide in 10 ml of dichloromethane and stirred for 4 hours at room temperature. For working-up, the precipitated urea is filtered off, the filtrate is diluted with 40 ml of dichloromethane and washed with 40 ml each of 0.5N NaOH, 0.5N HCl and saturated sodium chloride solution, dried on sodium sulfate and concentrated by evaporation i.vac. The residue that remains after removal of the solvent i.vac. is chromatographed. Gradient chromatography on 200 g of silica gel 60 (dichloromethane→dichloromethane/methanol 95:5) yields 180 mg (64%) of N-(N-(N-(N -(valeroyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [11β,21-dihydroxy-3,20-dioxo-6α-methyl-17-propionyloxy-pregna-1,4-dien -21-yl] ester and, after recrystallization, 157 mg (56%) in crystalline form from dichloromethane/diisopropyl ether/hexane.

Provenance & Evidence