Cesium carbonate → [1-(2-Fluoro-4-{1-oxo-6-[(R)-1-(tetrahydrofuran-2-yl)methoxy]-1H-isoquinolin-2-yl}-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

HRID 69493Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 69493
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH2:19][C@H:20]4[CH2:24][CH2:23][CH2:22][O:21]4)[CH:14]=3)[C:9]2=[O:25])=[CH:4][C:3]=1[F:26].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:79]([O:83][C:84](=[O:91])[NH:85][CH:86]1[CH2:90][CH2:89][NH:88][CH2:87]1)([CH3:82])([CH3:81])[CH3:80]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:79]([O:83][C:84](=[O:91])[NH:85][CH:86]1[CH2:90][CH2:89][N:88]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH:17]=[CH:16][C:15]4[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH2:19][C@H:20]5[CH2:24][CH2:23][CH2:22][O:21]5)[CH:14]=4)[C:9]3=[O:25])=[CH:4][C:3]=2[F:26])[CH2:87]1)([CH3:82])([CH3:80])[CH3:81]

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 689912162-(4-Bromo-3-fluorophenyl)-6-[(R)-1-(tetrahydrofuran-2-yl)methoxy]-2H-isoquinolin-1-one

Produkt 1

HCID 68993565[1-(2-Fluoro-4-{1-oxo-6-[(R)-1-(tetrahydrofuran-2-yl)methoxy]-1H-isoquinolin-2-yl}-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 2-(4-bromo-3-fluorophenyl)-6-[(R)-1-(tetrahydrofuran-2-yl)methoxy]-2H-isoquinolin-1-one (75 mg), palladium(II) acetate (3 mg), BINAP (14 mg), cesium carbonate (82 mg) and pyrrolidin-3-yl-carbamic acid tert-butyl ester (48 mg) in degassed toluene (2 mL) was stirred for 18 h at 100° C. The mixture was diluted with ethyl acetate, filtered and the filtrate was concentrated. The residue was purified by preparative HPLC. In this way the product was obtained with molecular weight 523.61 (C29H34FN3O5); MS (ESI): 524 (M+H+).

Aufarbeitung

  1. filtrationfiltered
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified by preparative HPLC
  4. customIn this way the product was obtained with molecular weight 523.61 (C29H34FN3O5)

Quellen und Nachweise

ORD-Eintrag
ord-e95394959a81428e9a7a7fe1aab49321
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822495B2

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