Diisopropylethylamine → tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1486089Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1486089
[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:19])OC(C)(C)C)[C:8](=[O:20])[NH:7][C:6]2[CH:21]=[CH:22][C:23]([C:25]#[N:26])=[CH:24][C:5]1=2)(=[O:3])[CH3:2].[C:27]([N:34]([CH3:40])[C@H:35](C(O)=O)[CH3:36])([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>Cl.O1CCOCC1.CCOCC.CCOC(C)=O>[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:19])[C@@H:35]([N:34]([CH3:40])[C:27](=[O:28])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[CH3:36])[C:8](=[O:20])[NH:7][C:6]2[CH:21]=[CH:22][C:23]([C:25]#[N:26])=[CH:24][C:5]1=2)(=[O:3])[CH3:2]

Komponenten

9

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 131736779tert-butyl(2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

Produkt 1

HCID 90088957tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 313Hydrochloric AcidLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A rt solution of tert-butyl(2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (144 mg, 402 μmol) in 4 M HCl in dioxane (2.01 ml) was stirred for 2 h. The reaction was diluted with Et2O and the solids were collected by vacuum filtration, taken up in DMF (1.34 ml), and Boc-N-methyl-L-alanine (89.9 mg, 442 μmol), N,N-diisopropylethylamine (278 μl, 1.61 mmol), and HBTU (168 mg, 442 μmol) were added at 0° C. The reaction was stirred at rt for 30 min, then diluted with EtOAc, washed with H2O, sat. aq. NaHCO3, and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (123 mg, 69%) as a white solid. MS m/z 466 (MNa)+.

Aufarbeitung

  1. filtrationthe solids were collected by vacuum filtration
  2. washwashed with H2O, sat. aq. NaHCO3, and sat. aq. NaCl
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-86b18467d4bd4c968caad427cf8768f5
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09422331B2

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