反应详情

(R)-tert-Butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acid (280 mg, 0.73 mmol), 2-((S)-2-amino-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester (203 mg, 0.66 mmol) (prepared as described in example 10, step 1), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (191 mg, 1.0 mmol) and 1-hydroxybenzotriazole hydrate (135 mg, 1.0 mmol) were combined in dichloromethane (5 mL) and stirred overnight at room temperature. The resulting solution was poured into ethyl acetate and washed with 0.2 M aqueous hydrochloric acid, water, brine and dried over magnesium sulfate. The solvents were removed and the crude was purified by chromatography over silica gel gradient eluted between 40% and 50% v/v ethyl acetate in hexane to give 2-((S)-2-{(R)-2-tert-butoxycarbonylamino-2-[4-((S)-2,2-dimethyl-[1,3]dioxolan4-ylmethoxy)-phenyl]-acetylamino}-3-phenyl-propionylamino)-thiazole-4-carboxylic acid methyl ester as a foam (170 mg, 38%).

1. washwashed with 0.2 M aqueous hydrochloric acid, water, brine
2. dry with materialdried over magnesium sulfate
3. customThe solvents were removed
4. customthe crude was purified by chromatography over silica gel gradient
5. washeluted between 40% and 50% v/v ethyl acetate in hexane