StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

Phosphorus oxybromide → 2-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)-8-(trifluoromethyl)quinazolin-4-amine

HRID 473181
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 473181
[F:1][C:2]([F:25])([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=1)[C:3]1[N:12]=[C:11](O)[C:10]2[C:5](=[C:6]([C:14]([F:17])([F:16])[F:15])[CH:7]=[CH:8][CH:9]=2)[N:4]=1.P(Br)(Br)(Br)=O.CCN(C(C)C)C(C)C.[CH3:40][C:41]1[NH:45][N:44]=[C:43]([NH2:46])[CH:42]=1>CN(C=O)C.C1(C)C=CC=CC=1>[F:1][C:2]([F:25])([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=1)[C:3]1[N:12]=[C:11]([NH:46][C:43]2[CH:42]=[C:41]([CH3:40])[NH:45][N:44]=2)[C:10]2[C:5](=[C:6]([C:14]([F:17])([F:16])[F:15])[CH:7]=[CH:8][CH:9]=2)[N:4]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 24613Phosphorus oxybromideHCID 81531DiisopropylethylamineHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 178517776HCID 178517776, Verbindung

Produkt 1

HCID 568486932-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)-8-(trifluoromethyl)quinazolin-4-amineAusbeute 20,1 %

Reagenzien, Katalysatoren, Lösungsmittel

2
HCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

To 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-(trifluoromethyl)quinazolin-4-ol (121 mg, 0.34 mmol) were added phosphoryl tribromide (890 mg) and toluene (1 mL) followed by DIEA (0.117 mL, 0.67 mmol). The mixture was heated at 105° C. for 1 h. The mixture was cooled and partitioned between EtOAc and saturated aq sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. To the residue was added a solution of 5-methyl-1H-pyrazol-3-amine (150 mg, 1.5 mmol) in DMF (4 mL) and the mixture was stirred at rt for 1.5 h. The crude mixture was purified by preparative HPLC (Varian diphenyl reverse phase column, eluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/H2O) to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-N-(5-methyl-1H-pyrazol-3-yl)-8-(trifluoromethyl)quinazolin-4-amine (30 mg, 20%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.19 (s, 3H) 6.03 (s, 1H) 7.77 (t, J=7.91 Hz, 1H) 7.96-8.06 (m, 2H) 8.27 (d, J=7.53 Hz, 1H) 8.67 (s, 1H) 8.97 (d, J=8.29 Hz, 1H) 11.00 (br s, 1H) 12.18 (br s, 1 H); LC-MS (ESI) m/z 439 (M+H)+.

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. custompartitioned between EtOAc and saturated aq sodium bicarbonate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude mixture was purified by preparative HPLC (Varian diphenyl reverse phase column
  6. washeluting with a gradient of solvent B=0.05% HOAc/ACN and solvent A=0.05% HOAc/H2O)

Quellen und Nachweise

ORD-Eintrag
ord-6288a71a4e9046a882a08dc8484cef54
Quelldatensatz
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08633207B2

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion