反应详情

First, the amine compound N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(morpholin-4-yl)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide was produced as sodium trifluoroacetate, analogous to the synthesis described in example 15 by means of coupling N-(tert.-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (intermediate 39) with morpholine in the presence of EDC and HOBt, followed by cleavage of the Boc-protected group with the help of trifluoroacetic acid. Out of 30 mg (0.033 mmol) of this compound 22 mg (76% o. th.) of the title compound were then obtained in analogy to the production of example 1, by means of treatment with 4-ketobutyric acid in the presence of sodium cyanoborohydride.