Hydrochloric Acid → (2S, 4S, 5S)-5-{N-[N-Morpholinoacetyl-3-(1-naphthyl)-L-alanyl]-3-(4-thiazolyl)-L-alanyl}amino-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-[2(S)-methylbutyl]hexanamide

Participants

Reaction Steps

A mixture of 150 mg (0.25 mmoles) of (2S, 4S, 5S)-5-{N-[N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]amino}-6-cyclohexyl-4-hydroxy-2-(1-hydroxy-1-methylethyl)-N-[2(S)-methylbutyl]hexanamide (prepared as described in Example 1) in 5 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes. At the end of this time, the solvent was removed by distillation under reduced pressure, and diethyl ether was added to the residue. The solvent was then again removed by distillation under reduced pressure. This operation was repeated in total three times, and then the final residue was dried under vacuum for 8 hours. The dried material was suspended in 10 ml of anhydrous tetrahydrofuran, and then 100 mg (0.29 mmoles) of N-morpholinoacetyl-3-(1-naphthyl)-L-alanine were added to the resulting suspension, followed by 0.04 ml (0.26 mmoles) of 95% diethyl cyanophosphate and 0.11 ml (0.79 mmoles) of triethylamine, all whilst ice-cooling and under an atmosphere of nitrogen. The mixture was then stirred for 8 hours, after which the solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel thin layer chromatography (using a 10:1 by volume mixture of methylene chloride and methanol as eluent), to give 150 mg (yield 73%) of the title compound as white crystals, melting at 141°-143° C.

Provenance & Evidence