4-Methylmorpholine → N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosyl-N-{(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropyl}-D-alaninamide

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Reaction Steps

tert-Butyl-[(1S)-2-(D-alanylamino)-1-benzylethyl]carbamate (described in PC33903A Preparation 36; 3.43 g, 9.94 mmol) and N-(tert-butoxycarbonyl)-2,6-dimethyl-L-tyrosine (described in BioOrg. Med. Chem. Letts, 2003, p 599; 2.92 g, 9.25 mmol) were added sequentially to a stirred solution of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride salt (2.29 g, 11.9 mmol), 1-hydroxybenzotriazole monohydrate (1.57 g, 10.2 mmol) and N-methylmorpholine (1.01 g, 9.94 mmol) in DMF (70 mL) at room temperature under a nitrogen atmosphere. The mixture was stirred at room temperature for 16 h and then diluted with 280 mL of EtOAc and washed with 280 mL of a 10% aqueous solution of citric acid, 280 mL of water, 280 mL of a 3% aqueous solution of sodium bicarbonate, and finally 200 mL of a saturated aqueous brine solution. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give 6.2 g (92%) of a white foam of the title compound, which was used with no further purification.

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