Cesium fluoride → HCID 178461552, Verbindung

HRID 876517Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 876517
Br[C:2]1[NH:3][C:4]2[C:9]([N:10]=1)=[C:8]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)[N:7]=[C:6]([N:17]1[CH2:22][C@@H:21]([CH3:23])[O:20][C@@H:19]([CH3:24])[CH2:18]1)[N:5]=2.[F-].[Cs+].[OH:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1>C(#N)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:24][C@@H:19]1[O:20][C@H:21]([CH3:23])[CH2:22][N:17]([C:6]2[N:5]=[C:4]3[C:9]([N:10]=[C:2]([C:32]4[CH:33]=[C:28]([OH:27])[CH:29]=[CH:30][CH:31]=4)[NH:3]3)=[C:8]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[N:7]=2)[CH2:18]1

Komponenten

6

Edukt 3

HCID 25953Cesium fluorideHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 178461551HCID 178461551, Verbindung

Produkt 1

HCID 178461552HCID 178461552, VerbindungAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 18373917Acetonitrile--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
115 °C

Versuchsvorschrift

To a round bottom flask were added, 8-bromo-2-((2S,6R)-2,6-dimethyl-morpholin-4-yl)-6-morpholin-4-yl-9H-purine (38.2 mg, 0.096 mmol), cesium fluoride 58.4 mg, 0.39 mmol), 3-hydroxyphenylboronic acid (39.8 mg, 0.29 mmol) and tetrakis(triphenylphosphine)palladium (8.9 mg, 7.69 mmol) followed by 1 mL of acetonitrile/water solvent mixture (10/1 ratio). Suspension was heated to 115° C. and stirred overnight. Upon completion of the reaction, the suspension was cooled and solids filtered off. Solvent was removed under reduced pressure and the crude was purified directly by preparative HPLC to provide 3-[2-((2S,6R)-2,6-dimethyl-morpholin-4-yl)-6-morpholin-4-yl-9H-purin-8-yl]-phenol (18.5 mg, 47%) as yellow solid. LC/MS analysis method 7, mass (ES+) m/z 411.2, retention time 1.40 min. 1HNMR (CDCl3): 7.34 (1H, d), 7.24 (2H, m), 6.87 (1H, d), 4.35 (2H, d), 4.30 (4H, brs), 3.80 (4H, m), 3.57 (2H, m), 2.53 (2H, t), 1.16 (6H, d).

Aufarbeitung

  1. additionTo a round bottom flask were added
  2. customUpon completion of the reaction
  3. temperaturethe suspension was cooled
  4. filtrationsolids filtered off
  5. customSolvent was removed under reduced pressure
  6. customthe crude was purified directly by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-361bff02d0ff49b288ea54eab87d5403
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987257B2

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