Dimethyl Sulfoxide → HCID 59631572, Verbindung

HRID 1431635

Reaktionsgleichung

Reaktionsgleichung von HRID 1431635
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]([NH:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([F:24])=[CH:21][CH:22]=4)[N:17]=[C:16]([C:25]4[CH:30]=[C:29]([N+]([O-])=O)[CH:28]=[CH:27][C:26]=4[S:34]([CH3:37])(=[O:36])=[O:35])[C:15]=3[CH3:38])=[CH:11][C:10]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[CH:9][N:8]=2)[CH2:3][CH2:2]1.C(=N/[OH:53])/C1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]([NH:13][C:14]3[C:23]4[C:18](=[CH:19][C:20]([F:24])=[CH:21][CH:22]=4)[N:17]=[C:16]([C:25]4[CH:30]=[C:29]([OH:53])[CH:28]=[CH:27][C:26]=4[S:34]([CH3:37])(=[O:35])=[O:36])[C:15]=3[CH3:38])=[CH:11][C:10]([N:39]3[CH2:40][CH2:41][O:42][CH2:43][CH2:44]3)=[CH:9][N:8]=2)[CH2:3][CH2:2]1

Komponenten

6

Edukt 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 5324470Syn-benzaldehyde oximeHCID 59631575HCID 59631575, Verbindung

Produkt 1

HCID 59631572HCID 59631572, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

The N-(2,5-dimorpholinopyridin-3-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)-5-nitrophenyl)quinolin-4-amine (3.0 mg, 4.8 μmol), (Z)-benzaldehyde oxime (1.0 μL, 9.6 μmol), 325 mesh potassium carbonate (2.7 mg, 0.019 mmol) and DMSO (9.6 μL) was heated in a microwave reactor for 45 min at 100° C. The reaction was cooled and diluted with water. The mixture was extracted with EtOAc (2×35 mL). The combined organic layers were washed with brine (1×20 mL) and dried over magnesium sulfate. The crude material was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 90% over 20 min to provide 3-(4-(2,5-dimorpholinopyridin-3-ylamino)-7-fluoro-3-methylquinolin-2-yl)-4-(methylsulfonyl)phenol after extracting with satd sodium bicarbonate solution. 1H NMR (CDCl3) δ ppm 8.00 (1H, br. s.), 7.94 (1H, d, J=8.8 Hz), 7.84 (1H, d, J=7.8 Hz), 7.65 (1H, br. s.), 7.43 (1H, t, J=8.2 Hz), 6.91 (1H, d, J=8.4 Hz), 6.85 (1H, br. s.), 6.52 (1H, br. s.), 3.83-4.05 (4H, m), 3.76 (4H, t, J=4.7 Hz), 3.42 (2H, br. s.), 2.93-3.20 (9H, m), 1.99 (3H, br. s.). Mass Spectrum (ESI) m/e=594.2 (M+1).

Aufarbeitung

  1. temperatureThe reaction was cooled
  2. extractionThe mixture was extracted with EtOAc (2×35 mL)
  3. washThe combined organic layers were washed with brine (1×20 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe crude material was purified by reverse-phase preparative HPLC
  6. customover 20 min

Quellen und Nachweise

ORD-Eintrag
ord-b032025227e64a7c91edfa3f847b938a
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940724B2

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