1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(4-tert-butoxycarbonylamino-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

Participants

Reaction Steps

To a solution of (R)-tert-butoxycarbonylamino-(4-tert-butoxycarbonylamino-phenyl)-acetic acid (420 mg, 1.13 mmol) and (2S,3S)-2-(2-amino-3-phenyl-butyrylamino)-thiazole-4-carboxylic acid methyl ester (300 mg, 0.94 mmol) (prepared as described in Example 7) in dichloromethane (50 mL) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (220 mg, 1.13 mmol) at 0° C. The reaction mixture was allowed to warm to ambient temperature slowly, stirred overnight and then partitioned between dichloromethane and water. The organic layer was dried over sodium sulfate, filtered and concentrated to give the crude product. Purification by chromatography over silica gel gradient eluted between 0 and 60% ethyl acetate in hexanes followed by a precipitation of the product from dichloromethane with excess hexanes gave 2-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(4-tert-butoxycarbonylamino-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester as a white solid (520 mg, 82%).

Provenance & Evidence