1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-{[1-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]amino}-2-cyclopropyl-propionic acid tert-butyl ester

HRID 1481230Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1481230
[C:1]([O:5][C:6](=[O:13])[CH:7]([CH:10]1[CH2:12][CH2:11]1)[CH2:8][NH2:9])([CH3:4])([CH3:3])[CH3:2].C[O:15][C:16]([C:18]1[N:19]=[C:20]([C:37]#[N:38])[C:21]2[C:26]([C:27]=1[OH:28])=[CH:25][CH:24]=[C:23]([O:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[CH:22]=2)=O.C1CCN2C(=NCCC2)CC1>CC(N(C)C)=O>[C:1]([O:5][C:6](=[O:13])[CH:7]([CH:10]1[CH2:12][CH2:11]1)[CH2:8][NH:9][C:16]([C:18]1[N:19]=[C:20]([C:37]#[N:38])[C:21]2[C:26]([C:27]=1[OH:28])=[CH:25][CH:24]=[C:23]([O:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[CH:22]=2)=[O:15])([CH3:4])([CH3:2])[CH3:3]

Komponenten

5

Edukt 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 89812868Tert-butyl 3-amino-2-cyclopropylpropanoateHCID 898130491-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester

Produkt 1

HCID 898129723-{[1-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]amino}-2-cyclopropyl-propionic acid tert-butyl esterAusbeute 45,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A mixture of 3-amino-2-cyclopropyl-propionic acid tert-butyl ester (20 mg), 1-cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester (15 mg) and DBU (10 mg) in DMA (0.3 mL) was heated in an oil bath (150° C.) for 1 h. The reaction mixture was then partitioned between EtOAc and diluted HCl solution, EtOAc phase was separated and washed with water, diluted NaCl solution and dried over anhydrous sodium sulfate solution, filtered, concentrated and silica gel column purified to give desired product as brown solid (10 mg). LC-MS ESI+: 492 (M+1)+.

Aufarbeitung

  1. customThe reaction mixture was then partitioned between EtOAc and diluted HCl solution, EtOAc phase
  2. customwas separated
  3. washwashed with water, diluted NaCl solution
  4. dry with materialdried over anhydrous sodium sulfate solution
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customsilica gel column purified

Quellen und Nachweise

ORD-Eintrag
ord-ce9d785fbbd84f2aa9de6a35fcaf4c49
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409892B2

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