Cesium carbonate → (3aR,6aR)-3-(6-Chloro-2-morpholinopyrimidin-4-yl)tetrahydrofuro[3,4-d]oxazol-2(3H)-one

HRID 538924

Reaktionsgleichung

Reaktionsgleichung von HRID 538924
[O:1]1[C@H:5]2[CH2:6][O:7][CH2:8][C@H:4]2[NH:3][C:2]1=[O:9].[Cl:10][C:11]1[CH:16]=[C:15](Cl)[N:14]=[C:13]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].C([O-])(O)=O.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[Ar]>[Cl:10][C:11]1[N:12]=[C:13]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:14]=[C:15]([N:3]2[C@@H:4]3[CH2:8][O:7][CH2:6][C@@H:5]3[O:1][C:2]2=[O:9])[CH:16]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholineHCID 55303430(3aR,6aR)-tetrahydrofuro[3,4-d]oxazol-2(3H)-one

Produkt 1

HCID 86694354(3aR,6aR)-3-(6-Chloro-2-morpholinopyrimidin-4-yl)tetrahydrofuro[3,4-d]oxazol-2(3H)-oneAusbeute 88,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 86694355Argon 4,5-bis(diphenylphosphino)-9,9-dimethylxantheneKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a solution of (3aR,6aR)-tetrahydrofuro[3,4-d]oxazol-2(3H)-one (500 mg, 3.87 mmol), 4-(4,6-dichloropyrimidin-2-yl)morpholine (1088 mg, 4.65 mmol) and Cs2CO3 (2.14 g, 6.58 mmol) in dioxane (20 mL) was added after degassing with argon 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (157 mg, 0.271 mmol) and Pd2(dba)3 (70.9 mg, 0.077 mmol) and the reaction mixture was heated for 6 h at 85° C. The reaction mixture was added to 10% aqueous NaHCO3 solution and extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was triturated in MeOH overnight, filtered off and dried to afford the title compound as a colorless solid (1.12 g, 87%): tR=0.92 min (LC-MS 3); ESI-MS: 327, 329 [M+H]+ (LC-MS 3).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washCombined extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was triturated in MeOH overnight
  7. filtrationfiltered off
  8. customdried

Quellen und Nachweise

ORD-Eintrag
ord-bda22b43dbb34821baabd86acef054a1
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865894B2

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