Sodium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4'-cyano-3'-methylbiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216946

Reaktionsgleichung

Reaktionsgleichung von HRID 216946
[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=1.Br[C:39]1[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[C:41]([CH3:47])[CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C>[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:39]2[CH:46]=[CH:45][C:42]([C:43]#[N:44])=[C:41]([CH3:47])[CH:40]=2)=[CH:7][CH:6]=1

Komponenten

5

Edukt 3

HCID 10340Sodium CarbonateHCID 1442674-Bromo-2-methylbenzonitrileHCID 59568592(S)-tert-Butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Produkt 1

HCID 59568569(S)-tert-Butyl 4-(1-amino-3-(4'-cyano-3'-methylbiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateAusbeute 72,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

(S)-tert-Butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 180 mg) and 4-bromo-2-methylbenzonitrile (72 mg) in acetonitrile (8 mL) were treated with an aqueous solution of sodium carbonate (2M, 0.348 mL) and nitrogen was bubbled through the mixture. 1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added and the mixture was heated at 85° C. for 18 h. The mixture was concentrated and purified by chromatography on silica eluting with 50 to 100% ethyl acetate/isohexane to afford the sub-titled compound (127 mg).

Aufarbeitung

  1. customwas bubbled through the mixture
  2. addition1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added
  3. concentrationThe mixture was concentrated
  4. custompurified by chromatography on silica eluting with 50 to 100% ethyl acetate/isohexane

Quellen und Nachweise

ORD-Eintrag
ord-dd9b544397ed4a74a27458fd7019ec8b
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193239B2

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