Potassium Acetate → (S)-tert-Butyl 4-(1-cyano-2-(4-(1-oxoisoindolin-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216939Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 216939
[C:1]([C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)#[N:2].C([O-])(=O)C.[K+].CC1(C)C(C)(C)OB([C:42]2[CH:43]=[C:44]3[C:48](=[CH:49][CH:50]=2)[C:47](=[O:51])[NH:46][CH2:45]3)O1>C(#N)C.O>[C:1]([C@@H:3]([NH:12][C:13]([C:15]1([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:42]2[CH:43]=[C:44]3[C:48](=[CH:49][CH:50]=2)[C:47](=[O:51])[NH:46][CH2:45]3)=[CH:7][CH:6]=1)#[N:2]

Komponenten

6

Edukt 3

HCID 517044Potassium AcetateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 59568614(S)-tert-Butyl 4-(1-cyano-2-(4-iodophenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Produkt 1

HCID 59568570(S)-tert-Butyl 4-(1-cyano-2-(4-(1-oxoisoindolin-5-yl)phenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateAusbeute 60,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of (S)-tert-butyl 4-(1-cyano-2-(4-iodophenyl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 15, step (i), 260 mg), potassium acetate (153 mg) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (162 mg) in acetonitrile (10 mL) and water (5 mL) under a nitrogen atmosphere, was treated with 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (10 mg) and the mixture stirred and heated at 90° C. for 18 h. The reaction mixture was cooled to room temperature and diluted with water. The products were extracted into ethyl acetate (2×100 mL) and the combined extracts dried over magnesium sulphate and concentrated to dryness. The residue was purified by chromatography on silica eluting with ethyl acetate to afford the sub-titled compound (160 mg).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe products were extracted into ethyl acetate (2×100 mL)
  3. dry with materialthe combined extracts dried over magnesium sulphate
  4. concentrationconcentrated to dryness
  5. customThe residue was purified by chromatography on silica eluting with ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-f5844caf2b42412188bd4b2d0ebfbb7c
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193239B2

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