(S)-tert-butyl 4-(4-(5-bromopyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylate → (S)-tert-butyl 4-(4-(5-tert-butylpyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 1187774Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1187774
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:30]=[CH:29][C:12]([CH2:13][CH2:14][C@H:15]3[CH2:19][O:18][C:17]([CH3:21])([CH3:20])[N:16]3[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[Br-].[C:32]([Zn+])([CH3:35])([CH3:34])[CH3:33]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:32]([C:2]1[CH:3]=[N:4][C:5]([NH:8][C:9]2[CH:30]=[CH:29][C:12]([CH2:13][CH2:14][C@H:15]3[CH2:19][O:18][C:17]([CH3:21])([CH3:20])[N:16]3[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:11][CH:10]=2)=[N:6][CH:7]=1)([CH3:35])([CH3:34])[CH3:33]

Komponenten

5

Edukt 2

HCID 67501307(S)-tert-butyl 4-(4-(5-bromopyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylateHCID 178455669HCID 178455669, Verbindung

Produkt 1

HCID 67502410(S)-tert-butyl 4-(4-(5-tert-butylpyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylateAusbeute 9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
22 °C

Versuchsvorschrift

To (S)-tert-butyl 4-(4-(5-bromopyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylate (100 mg) and bis(tri-t-butylphosphine)palladium(0) (21.4 mg) in THF (10 ml) under argon was added tert-butylzinc(II) bromide (1.26 ml, 0.5 M solution in THF). The reaction mixture was stirred at 22° C. for 1 hour. The reaction was quenched by addition of EtOAc then washed sequentially with saturated aqueous ammonium chloride solution and 1 N aqueous sodium bicarbonate solution. The phases were separated and the organic phase was dried over MgSO4, filtered and then concentrated in vacuo. The crude material was purified by preparative HPLC (Column: Zorbax 5 micron C18 50×20, flow rate: 30 ml/min; eluant gradient: water (+0.1% formic acid)/acetonitrile (80%-20% to 5%-95%)) to afford (S)-tert-butyl 4-(4-(5-tert-butylpyrimidin-2-ylamino)phenethyl)-2,2-dimethyloxazolidine-3-carboxylate (8.4 mg, 9%) as a yellow oil. MS (ISP): 455.5 ([M+H]+).

Aufarbeitung

  1. customThe reaction was quenched by addition of EtOAc
  2. washthen washed sequentially with saturated aqueous ammonium chloride solution and 1 N aqueous sodium bicarbonate solution
  3. customThe phases were separated
  4. dry with materialthe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by preparative HPLC (Column: Zorbax 5 micron C18 50×20, flow rate: 30 ml/min; eluant gradient: water (+0.1% formic acid)/acetonitrile (80%-20% to 5%-95%))

Quellen und Nachweise

ORD-Eintrag
ord-b9072b6d50664f35983ddc40d4476079
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08673950B2

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