Diisopropylethylamine → (S)-Methyl 6-amino-2-((tert-butoxycarbonyl)amino)hexanoate

HRID 1625695Notes

Reaction equation

HRID 1625695 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:7]([O:9][CH3:10])=[O:8].[O:19]=[C:20]1[CH2:23][CH:22]([C:24](O)=[O:25])[CH2:21]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:7]([O:9][CH3:10])=[O:8].[C:15]([O:14][C:12]([NH:11][C@@H:6]([CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:24]([CH:22]1[CH2:23][C:20](=[O:19])[CH2:21]1)=[O:25])[C:7]([O:9][CH3:10])=[O:8])=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 49133583-Oxocyclobutane-1-carboxylic acidHCID 7018772(S)-Methyl 6-amino-2-((tert-butoxycarbonyl)amino)hexanoateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 2

HCID 7018772(S)-Methyl 6-amino-2-((tert-butoxycarbonyl)amino)hexanoateHCID 58481198(S)-methyl 2-(tert-butoxycarbonylamino)-6-(3-oxocyclobutanecarboxamido)hexanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 1M stock solution of (S)-methyl 6-amino-2-(tert-butoxycarbonylamino)hexanoate in 20 mL DMF was prepared, and used. A 2 mL aliquot of the (S)-methyl 6-amino-2-(tert-butoxycarbonylamino)hexanoate stock solution, 3-oxocyclobutanecarboxylic acid (2) (Parkway *BX-102, 283 mg), HATU (800 mg), DIEA (1.0 mL) and 8 mL DMF were combined in a 40 mL glass vial, and stirred at ambient temperature overnight. The LC-MS analysis revealed a complete reaction. The reaction mixture was diluted with EtOAc, washed successively with water, sat aq. NaCl, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel flash chromatography (hexanes/EtOAc), affording (S)-methyl 2-(tert-butoxycarbonylamino)-6-(3-oxocyclobutanecarboxamido)hexanoate (TU3000-140) as a clear viscous oil. MS (ESI+): calcd. 379.18. found 379.20 (MNa+), calcd. 257.15. found 257.20((M-Boc)H+). H-NMR (400 MHz, DMSO-d6):1.245 (4H, m), 1.371 (9H, s), 1.579 (2H, m), 3.065 (3H, m), 3.135 (4H, m), 3.608 (3H, s), 3.895 (1H, m), 7.209 (1 h, d, J=8.0 Hz), 8.123 (1H, t, J=5.4 Hz). C-NMR (100 MHz, DMSO-d6): 22.850, 27.185, 28.111, 28.551, 30.209, 38.276, 50.859, 51.639, 53.412, 53.529, 78.137, 155.507, 172.992, 173.167, 205.576.

Workup

  1. customa complete reaction
  2. washwashed successively with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by silica gel flash chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-32cd3f556db648e5935dc9d00fd6ec01
Source dataset
uspto-grants-2014_07
Patent number
US08785151B2

Reaction notes

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