Cesium carbonate → HCID 86679608, Verbindung

HRID 577662Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 577662
Cl[C:2]1[N:3]=[C:4]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)[C:5]2[C:10]([F:11])=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1.[CH3:30][N:31]1[CH:35]=[CH:34][C:33]([NH2:36])=[N:32]1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[F:11][C:10]1[C:5]2[C:4]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=3)=[N:3][C:2]([NH:36][C:33]3[CH:34]=[CH:35][N:31]([CH3:30])[N:32]=3)=[N:7][C:6]=2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:9]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 1372541-Methyl-3-aminopyrazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86679606HCID 86679606, Verbindung

Produkt 1

HCID 86679608HCID 86679608, VerbindungAusbeute 95,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

To a solution of 2-chloro-5-fluoro-4-(3-nitrophenoxy)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (483 mg, 1.1 mmol), in 1,4-dioxane (12 mL) was added 1-methyl-1H-pyrazol-3-amine (128 mg, 1.32 mmol), Cs2CO3 (717 mg, 2.2 mmol), Xantphos (66 mg, 0.11 mmol) and Pd2(dba)3 (101 mg, 0.11 mmol). The reaction vial was flushed with nitrogen, capped, stirred and heated at 140° C. in a microwave reactor for 45 min. After removing the reaction solvent, the residue was partitioned in EtOAc (120 mL) and water (20 mL). The organic layer was separated, washed with water (20 mL) and brine (10 mL), dried over Na2SO4 and evaporated. Purification via flash chromatography with a gradient of 0%-50% EtOAc in heptanes afforded the title compound (523 mg, 95% yield) as a thick oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.62 (s, 1H) 8.28-8.32 (m, 1H) 8.26 (d, J=8.06 Hz, 1H) 7.90-7.95 (m, 1H) 7.81-7.88 (m, 1H) 7.45 (br. s., 1H) 7.32 (d, J=2.27 Hz, 1H) 5.52 (s, 2H) 3.74 (s, 3H) 3.55-3.66 (m, 2H) 0.94 (t, J=8.18 Hz, 2H) 0.00 (s, 9H). m/z (APCI+) for C22H26FN7O4Si 500.1 (M+H)+.

Aufarbeitung

  1. customThe reaction
  2. customvial was flushed with nitrogen
  3. customcapped
  4. customAfter removing the reaction solvent
  5. customthe residue was partitioned in EtOAc (120 mL)
  6. customThe organic layer was separated
  7. washwashed with water (20 mL) and brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. customevaporated
  10. customPurification via flash chromatography with a gradient of 0%-50% EtOAc in heptanes

Quellen und Nachweise

ORD-Eintrag
ord-ebb5e206a3084a4c93c3c59aaaa088b3
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040547B2

Notizen zur Reaktion

Wird geladen…