Trifluoroacetic acid → Trifluoroacetate

HRID 1522047Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1522047
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[NH:15][C:16]([CH:18]4[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]4)=[CH:17][C:10]=23)O1.[CH2:32]([NH:39][C:40]1[CH:45]=[N:44][CH:43]=[C:42](Br)[N:41]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:72][C:73]([F:78])([F:77])[C:74]([OH:76])=[O:75]>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[CH2:32]([NH:39][C:40]1[CH:45]=[N:44][CH:43]=[C:42]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[NH:15][C:16]([CH:18]4[CH2:19][CH2:20][NH:21][CH2:22][CH2:23]4)=[CH:17][C:10]=23)[N:41]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[F:72][C:73]([F:78])([F:77])[C:74]([O-:76])=[O:75]

Komponenten

10

Edukt 5

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 90412512HCID 90412512, VerbindungHCID 90413258HCID 90413258, Verbindung

Produkt 2

HCID 84468TrifluoroacetateHCID 90412090HCID 90412090, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of Example 21A (400 mg, 0.94 mmol), N-benzyl-6-bromopyrazin-2-amine (297 mg, 1.12 mmol), bis(triphenylphosphine)palladium(ii) chloride (66 mg, 0.094 mmol), tricyclohexylphosphine (26 mg, 0.094 mmol) and cesium carbonate (921 mg, 2.8 mmol) was purged with nitrogen, then anhydrous dioxane (50 mL) was added. The mixture was heated at 100° C. overnight. The reaction was cooled to room temperature and filtrated; and the solid was washed with dichloromethane (200 mL). The filtrate was concentrated and purified by flash chromatography on silica gel using an ISCO Companion eluting with heptanes/ethyl acetate (30%) to give Boc-protected intermediate that was dissolved in CH2Cl2 (10 mL) then treated with trifluoroacetic acid (1 mL). The mixture was stirred at room temperature for 5 hours and concentrated. The residue was purified by reverse-phase HPLC on Zorbax XDB C-18 using a gradient of 5-40% acetonitrile/water (containing 0.1% trifluoroacetic acid) to afford the title compound as trifluoroacetate salt. MS (DCI/NH3) m/z 385 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltrated
  3. washand the solid was washed with dichloromethane (200 mL)
  4. concentrationThe filtrate was concentrated
  5. custompurified by flash chromatography on silica gel using an ISCO Companion
  6. washeluting with heptanes/ethyl acetate (30%)
  7. customto give Boc-protected intermediate
  8. concentrationconcentrated
  9. customThe residue was purified by reverse-phase HPLC on Zorbax XDB C-18

Quellen und Nachweise

ORD-Eintrag
ord-13c3b27ef2f14c85a0ded93e92e5180a
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073922B2

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