Toluene → 8-Cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline

HRID 473216

Reaktionsgleichung

Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([F:21])([F:20])[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[N:8]=[C:7]2[S:22][CH3:23].[CH:24]1(B(O)O)[CH2:26][CH2:25]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl.O>[CH:24]1([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[C:9]([C:12]([F:20])([F:21])[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=2)[N:8]=[C:7]3[S:22][CH3:23])[CH2:26][CH2:25]1

Komponenten

Reaktionsbedingungen

Temperatur: 100 °C

Versuchsvorschrift

To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (200 mg, 0.5 mmol), dichlorobis(tricyclohexylphosphine)palladium(II) (37 mg, 0.05 mmol), cyclopropylboronic acid (65 mg, 0.75 mmol) and K3PO4 (371 mg, 1.75 mmol) were added toluene (6 mL) and water (0.5 mL). The reaction vessel was evacuated and flushed with argon (3×), and then the mixture was heated at 100° C. for 4 h. The mixture was concentrated under reduced pressure onto Celite and the residue was purified by silica gel chromatography eluting with 10-50% EtOAc/hexanes to afford impure 8-cyclopropyl-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline (150 mg, 84%) which was used without further purification.

Aufarbeitung

customThe reaction vessel was evacuated
customflushed with argon (3×)
concentrationThe mixture was concentrated under reduced pressure onto Celite
customthe residue was purified by silica gel chromatography
washeluting with 10-50% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag: ord-4b691892610748fdaab7fcdc1a140446
Quelldatensatz: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08633207B2

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