1-Hydroxybenzotriazole → methyl (R)-8-[(S)-3-[(S)-2-[(S)-2-benzyloxycarbonylamino-propionylamino]-propionylamino]-2-methyl-propoxy]-2-tert.butoxycarbonylamino-1,2,3,4-tetrahydronaphthalene-2-carboxylate

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Reaction Steps

In analogy to Example 4.1.5.a, 70 mg (~0.178 mmol) of a mixture of methyl (R)-8-[(S)-3-amino-2-methyl-propoxy]-2-tert.butoxycarbonylamino-1,2,3,4-tetrahydronaphthalene-2-carboxylate and methyl (R)-2-tert.butoxycarbonylamino-8-[(S)-3-ethylamino-2-methyl-propoxy]-1,2,3,4-tetrahydronaphthalene-2-carboxylate in 1.5 ml of N,N-dimethylformamide were reacted at 0° for 3 hours with 78 mg (0.267 mmol) of Z-L-alanylalanine, 114 mg (0.356 mmol) of O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyl-uronium tetrafluoroborate (TPTU), 54.5 mg (0.356 mmol) of 1-hydroxybenzotriazole and 86 μl (0.534 mmol) of ethyldiisopropylamine. The residue was chromatographed on 20 g of silica gel with chloroform→chloroform/methanol (95:5→4:1), whereupon after drying in a high vacuum 30 mg (40.3%) of methyl (R)-8-[(S)-3-[[(S)-2-[(S)-2-benzyloxycarbonylamino-propionylamino]-propionyl]-ethyl-amino]-2-methyl-propoxy]-2-tert.butoxycarbonylamino-1,2,3,4tetrahydronaphthalene-2-carboxylate, [MS (ISP): 697.6 (M+H+ ; 100)], and then 26 mg (21.8%) of methyl (R)-8-[(S)-3-[(S)-2-[(S)-2-benzyloxycarbonylamino-propionylamino]-propionylamino]-2-methyl-propoxy]-2-tert.butoxycarbonylamino-1,2,3,4-tetrahydronaphthalene-2-carboxylate [MS (ISP): 535.5 (M+H+ ; 100)] were obtained.

Provenance & Evidence