Diisopropylethylamine → tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxobutan-2-ylcarbamate

HRID 1055478Notes

Reaction equation

HRID 1055478 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:9][O:8][C:7]2[CH:10]=[CH:11][CH:12]=[CH:13][C:6]=2[N:5]([CH2:14][C:15]2[C:24]3[C:19](=[CH:20][C:21]([Br:25])=[CH:22][CH:23]=3)[CH:18]=[CH:17][C:16]=2[O:26][CH3:27])[C:4]1=[O:28].[C:29]([O:33][C:34]([NH:36][C@@H:37]([CH2:41][CH3:42])[C:38](O)=[O:39])=[O:35])([CH3:32])([CH3:31])[CH3:30].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[Br:25][C:21]1[CH:20]=[C:19]2[C:24](=[CH:23][CH:22]=1)[C:15]([CH2:14][N:5]1[C:4](=[O:28])[C@@H:3]([NH:2][C:38](=[O:39])[C@@H:37]([NH:36][C:34](=[O:35])[O:33][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:41][CH3:42])[CH2:9][O:8][C:7]3[CH:10]=[CH:11][CH:12]=[CH:13][C:6]1=3)=[C:16]([O:26][CH3:27])[CH:17]=[CH:18]2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acidHCID 118574162HCID 118574162, compound

Product 1

HCID 131736374tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxobutan-2-ylcarbamateYield 94%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (S)-3-amino-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-2,3-dihydrobenzo[b][1,4]oxazepin-4(5H)-one hydrochloride (348 mg, 750 μmol), (S)-2-(tert-butoxycarbonylamino)butanoic acid (168 mg, 825 μmol), DIEA (519 μL, 3.00 mmol), and HBTU (313 mg, 825 μmol) in DMF (2.5 mL) was stirred at RT for 30 min. The mixture was diluted with EtOAc, washed with sat. NaHCO3, H2O, and brine brine, then dried over Na2SO4, and filtered. The filtrate was concentrated to give a residue that was purified by silica gel chromatography to provide tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxobutan-2-ylcarbamate (431 mg, 94%) as a white solid. MS m/z 634/636 (MNa)+

Workup

  1. washwashed with sat. NaHCO3, H2O, and brine brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customto give a residue that
  6. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-2b3c28a86aed45a8a52e2875d327b1ae
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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