1,4-Dioxane → 4-[2-Amino-6-(phenylamino)-4-pyrimidinyl]-2-fluorobenzonitrile

HRID 2367172Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2367172
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][C:4]=1[F:12])#[N:2].Cl[C:14]1[N:19]=[C:18]([NH2:20])[N:17]=[C:16]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:15]=1.O1CCOCC1.C([O-])(O)=O.[Na+]>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.O>[NH2:20][C:18]1[N:19]=[C:14]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([F:12])[CH:5]=2)[CH:15]=[C:16]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:17]=1

Komponenten

7

Edukt 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 14842836-chloro-N4-phenylpyrimidine-2,4-diamineHCID 2783130(4-Cyano-3-fluorophenyl)boronic acid

Produkt 1

HCID 513565894-[2-Amino-6-(phenylamino)-4-pyrimidinyl]-2-fluorobenzonitrileAusbeute 99,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To (4-cyano-3-fluorophenyl)boronic acid (197 mg, 1.20 mmol) and 6-chloro-N4-phenyl-2,4-pyrimidinediamine (330 mg, 1.50 mmol) in a sealable flask were added 1,4-dioxane (6 mL) and saturated aqueous NaHCO3 (3 mL). The mixture was degassed with nitrogen gas for 10 minutes. Pd(Ph3P)4 (86 mg, 0.075 mmol) was added and the reaction mixture was stirred overnight at 100° C. The mixture was poured onto EtOAc and water. The organic layer was separated and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. The resulting residue was chromatographed on SiO2 (gradient: 99:1:0.1 CHCl3/CH3OH/NH4OH to 90:10:1 CHCl3/CH3OH/NH4OH) to afford the title compound (366 mg). LC-MS (ES) m/z=306 [M+H]+.

Aufarbeitung

  1. customThe mixture was degassed with nitrogen gas for 10 minutes
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was further extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was chromatographed on SiO2 (gradient: 99:1:0.1 CHCl3/CH3OH/NH4OH to 90:10:1 CHCl3/CH3OH/NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-5a405296c1464bdaa02da2d070b049cb
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697685B2

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