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

HRID 356756Notes

Reaction equation

HRID 356756 reaction equation
[NH2:1][CH2:2][C@H:3]([CH3:28])[CH2:4][O:5][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[CH2:14][C@@:13]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]2.[C:29]([O:33][C:34]([NH:36][C@:37]1([C:55]([O:57]C)=O)[CH2:46]CC2C(=C(OC[C@@H](C)CNCC)C=CC=2)C1)=[O:35])(C)(C)C.F[B-](F)(F)F.[O:64]=[C:65]1[CH:70]=[CH:69]C=CN1OC(N(C)C)=[N+](C)C.ON1[C:84]2[CH:85]=[CH:86][CH:87]=[CH:88][C:83]=2N=N1.C([N:91](C(C)C)C(C)C)C>CN(C)C=O>[CH2:29]([O:33][C:34]([NH:36][C@@H:37]([CH3:46])[C:55]([NH:91][C@@H:70]([CH3:69])[C:65]([NH:1][CH2:2][C@H:3]([CH3:28])[CH2:4][O:5][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:15]=1[CH2:14][C@@:13]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])([C:16]([O:18][CH3:19])=[O:17])[CH2:12][CH2:11]2)=[O:64])=[O:57])=[O:35])[C:83]1[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 131720949methyl (R)-8-[(S)-3-amino-2-methyl-propoxy]-2-tert.butoxycarbonylamino-1,2,3,4-tetrahydronaphthalene-2-carboxylateHCID 131720950methyl (R)-2-tert.butoxycarbonylamino-8-[(S)-3-ethylamino-2-methyl-propoxy]-1,2,3,4-tetrahydronaphthalene-2-carboxylate

Product 1

HCID 131720948methyl (R)-8-[(S)-3-[(S)-2-[(S)-2-benzyloxycarbonylamino-propionylamino]-propionylamino]-2-methyl-propoxy]-2-tert.butoxycarbonylamino-1,2,3,4-tetrahydronaphthalene-2-carboxylateYield 21.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  1. customThe residue was chromatographed on 20 g of silica gel with chloroform→chloroform/methanol (95:5→4:1)
  2. dry with materialwhereupon 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)],

Sources & evidence

ORD record
ord-cd1a22e4424f4bfe9f0d693c84e5b66c
Source dataset
uspto-grants-1998_11
Patent number
US05837807

Reaction notes

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