Reaction Steps
To a suspension of (2R,6S,13aS,14aR,16aS,Z)-ethyl 6-amino-5,16-dioxo-2-(phenanthridin-6-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo [1,2-a][1,4]diazacyclopentadecine-14a-carboxylate, Hydrochloric Acid (Example 18b, 5.00 g, 8.24 mmol), 5-methylisoxazole-3-carboxylic acid (1.15 g, 9.06 mmol) and 2-(3H41,2,31triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (3.44 g, 9.06 mmol) in dichloromethane (82 ml) was added N-ethyl-N-isopropylpropan-2-amine (5.03 ml, 28.8 mmol). The mixture was stirred at rt for 2 h, and then quenched with saturated aqueous sodium carbonate solution. The organic layer was washed with 1N HCl, separated, filtered, dried over anhydrous magnesium sulfate and evaporated under reduced pressure to provide a white foam. This material was purified flash chromatography on silica gel (4:1 dichloromethane/ethyl acetate) to give (2R,6S,13aS,14aR,16aS,Z)-ethyl 6-(5-methylisoxazole-3-carboxamido)-5,16-dioxo-2-(phenanthridin-6-yloxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (4.5 g, 80% yield).
