Sodium Iodide → tert-butyl(S)-1-((3S,4S)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-5-(3-methoxypropanoyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1486059Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1486059
[CH3:1][O:2][CH2:3][CH2:4][C:5]([N:7]1[C@@H:13]([CH3:14])[C@H:12]([NH:15][C:16](=[O:28])[C@@H:17]([N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH3:18])[C:11](=[O:29])[NH:10][C:9]2[CH:30]=[CH:31][CH:32]=[CH:33][C:8]1=2)=[O:6].[Br:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[C:41]([CH2:45]Cl)=[C:40]([O:47][CH3:48])[CH:39]=[CH:38]2.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[C:41]([CH2:45][N:10]1[C:11](=[O:29])[C@@H:12]([NH:15][C:16](=[O:28])[C@@H:17]([N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:25])[CH3:23])[CH3:18])[C@H:13]([CH3:14])[N:7]([C:5](=[O:6])[CH2:4][CH2:3][O:2][CH3:1])[C:8]3[CH:33]=[CH:32][CH:31]=[CH:30][C:9]1=3)=[C:40]([O:47][CH3:48])[CH:39]=[CH:38]2

Komponenten

7

Edukt 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 118292643tert-butyl(S)-1-((2S,3S)-1-(3-methoxypropanoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Produkt 1

HCID 118292676tert-butyl(S)-1-((3S,4S)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-5-(3-methoxypropanoyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a rt solution of tert-butyl(S)-1-((2S,3S)-1-(3-methoxypropanoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (46 mg, 99.5 μmol) in DMF (249 μl) was added 6-bromo-1-(chloromethyl)-2-methoxynaphthalene (34.1 mg, 119 μmol), cesium carbonate (42.1 mg, 129 μmol), and sodium iodide (19.4 mg, 129 μmol). The reaction was stirred at rt for 16 h, then diluted with EtOAc, washed with H2O and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(S)-1-((3S,4S)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-5-(3-methoxypropanoyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (52.4 mg, 74%) as a white solid. MS m/z 733/735 (MNa)+.

Aufarbeitung

  1. washwashed with H2O and sat. aq. NaCl
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-1c1fa1e87f0347c1993247e165474045
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09422331B2

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