Sodium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4-(3-(2-methoxyethyl)-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216959

Reaktionsgleichung

Reaktionsgleichung von HRID 216959
[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:40]=[CH:41][C:42]2[O:46][C:45](=[O:47])[N:44]([CH2:48][CH2:49][O:50][CH3:51])[C:43]=2[CH:52]=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])[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:39]2[CH:40]=[CH:41][C:42]3[O:46][C:45](=[O:47])[N:44]([CH2:48][CH2:49][O:50][CH3:51])[C:43]=3[CH:52]=2)=[CH:7][CH:6]=1

Komponenten

5

Edukt 3

HCID 10340Sodium CarbonateHCID 579996905-Bromo-3-(2-methoxyethyl)benzo[d]oxazol-2(3H)-oneHCID 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 59568575(S)-tert-Butyl 4-(1-amino-3-(4-(3-(2-methoxyethyl)-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateAusbeute 23,5 %

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), 250 mg) in acetonitrile (8 mL) with 5-bromo-3-(2-methoxyethyl)benzo[d]oxazol-2(3H)-one (Example 24, step (i), 131 mg) was treated with an aqueous solution of sodium carbonate (2M, 0.483 mL). Nitrogen was bubbled through the solution and then 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added. The reaction mixture was heated at 85° C. for 18 h under nitrogen and allowed to cool to room temperature. Purification by chromatography on silica eluting with 50-100% ethyl acetate/isohexane as eluent afford the sub-titled compound (66 mg).

Aufarbeitung

  1. customNitrogen was bubbled through the solution
  2. addition1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (5 mg) was added
  3. temperatureto cool to room temperature
  4. customPurification by chromatography on silica eluting with 50-100% ethyl acetate/isohexane as eluent

Quellen und Nachweise

ORD-Eintrag
ord-92dea1d98c114cb88300daa1f16a9b2e
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193239B2

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