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-yl(methyl)carbamate

HRID 1055476Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1055476
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]([N:36]([CH3:43])[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]([N:36]([CH3:43])[C:34](=[O:35])[O:33][C:29]([CH3:30])([CH3:31])[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

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15689337(2S)-2-(((1,1-Dimethylethoxy)carbonyl)methylamino)butanoic acidHCID 118574162(S)-3-amino-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-2,3-dihydrobenzo[b][1,4]oxazepin-4(5H)-one hydrochloride

Produkt 1

HCID 131736373tert-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-yl(methyl)carbamateAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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 (54 mg, 116 μmol), (S)-2-(tert-butoxycarbonyl(methyl)amino)butanoic acid (27.8 mg, 128 μmol), DIEA (80.6 μl, 466 iumol), and HBTU (48.6 mg, 128 μmol) in DMF (388 μL) was stirred at RT for 30 min. The mixture was diluted with EtOAc, washed with sat. NaHCO3, H2O and 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-yl(methyl)carbamate (67.5 mg, 93%) as a white solid. MS m/z 648/650 (MNa)+

Aufarbeitung

  1. washwashed with sat. NaHCO3, H2O and 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

Quellen und Nachweise

ORD-Eintrag
ord-8d4076aa19934a51acee23a75eee7b3e
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394263B2

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