1-Hydroxybenzotriazole → methyl N-{5-[(N-acetyl-4-amino-3-isopropylphenylalanyl)amino]pentanoyl}methioninate

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Reaction Steps

A mixture of methyl N-acetyl-4-amino-3-isopropylphenylalaninate in 1N NaOH (4 mL) and methanol (2 mL) was stirred for 5 hours, concentrated under reduced pressure, taken up in a mixture of ethyl acetate and ethanol (3×30 mL, 1:1), dried (Na2SO4), filtered and concentrated under reduced pressure. MS (ESI) m/z=−263 (M−H)−. To a mixture of the residue (239 mg, 0.833 mmole), 2-(5-amino-pentanoylamino)-4-methylsulfanyl-butyric acid methyl ester (298 mg, 1.0 mmole), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (240 mg, 1.25 mmole) and N-hydroxybenzotriazole (169 mg, 1.25 mmole) in DMF (3 mL) was added triethyl amine (116 μL) and the mixture was stirred for 16 hours. The mixture was diluted with water and extracted with ethyl acetate (2×25 mL) then with chloroform (2×25 mL). The combined organics were dried (MgSO4), filtered, concentrated under reduced pressure and purified on silica gel eluting with 30% methanol/ethyl acetate to provide the titled compound (316 mg). MS (ESI) m/z=+509(M+H)+, 531 (M+Na)+.

Provenance & Evidence