4-(Trifluoromethoxy)benzylamine → 6-((6-((4-(trifluoromethoxy)benzyl)amino)pyridazin-3-yl)oxy)quinolin-2(1H)-one

HRID 77475

Reaktionsgleichung

Cl[C:2]1[N:7]=[N:6][C:5]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=[O:19])[CH:13]=[CH:12]3)=[CH:4][CH:3]=1.[F:20][C:21]([F:32])([F:31])[O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH2:28])=[CH:25][CH:24]=1.CC(C)([O-])C.[Na+]>O1CCOCC1.C[C@@H](P(C(C)(C)C)C(C)(C)C)[C]1[C](P(C2CCCCC2)C2CCCCC2)[CH][CH][CH]1.[CH]1[CH][CH][CH][CH]1.[Fe].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:20][C:21]([F:31])([F:32])[O:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH:28][C:2]2[N:7]=[N:6][C:5]([O:8][C:9]3[CH:10]=[C:11]4[C:16](=[CH:17][CH:18]=3)[NH:15][C:14](=[O:19])[CH:13]=[CH:12]4)=[CH:4][CH:3]=2)=[CH:25][CH:24]=1

Komponenten

Reaktionsbedingungen

Temperatur: 110 °C

Versuchsvorschrift

To a suspension of 6-((6-chloropyridazin-3-yl)oxy)quinolin-2(1H)-one (0.032 g, 0.117 mmol) in dioxane (2.0 mL) at room temperature was added 4-(trifluoromethoxy)benzylamine (0.091 mL, 0.585 mmol), (R)-(−)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine (3.28 mg, 5.85 μmol), palladium (II) acetate (1.313 mg, 5.85 μmol) and sodium-t-butoxide (0.014 mL, 0.164 mmol). The reaction mixture was stirred in a sealed tube at 110° C. overnight, then concentrated under vacuum to a yellow oil. This was purified by prep HPLC to yield 6-((6-((4-(trifluoromethoxy)benzyl)amino)pyridazin-3-yl)oxy)quinolin-2(1H)-one as a white solid (4 mg, 5%). 1H NMR (500 MHz, METHANOL-d4) δ ppm 7.96 (d, J=9.5 Hz, 2H), 7.67-7.34 (m, 8H), 6.68 (d, J=9.6 Hz, 1H), 4.59 (s, 2H). LCMS: R.T.=1.738 min; [M+H]+=429.08.

Aufarbeitung

concentrationconcentrated under vacuum to a yellow oil
customThis was purified by prep HPLC

Quellen und Nachweise

ORD-Eintrag: ord-9010a5994ac14c19992ca2d413c9fbc9
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08841301B2

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