Hydrochloric Acid → N-(1-methyl-1H-pyrazol-3-yl)-6-[(5-{[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]oxy}pyridin-2-yl)oxy] quinazoline-4-amine

HRID 1517279

Reaktionsgleichung

Reaktionsgleichung von HRID 1517279
CS([O:5][CH2:6][C@@H:7]([O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1)[CH3:8])(=O)=O.CC(C)([O-])C.[K+].[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([NH:28][C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36]([O:39][C:40]4[N:45]=[CH:44][C:43](O)=[CH:42][CH:41]=4)[CH:37]=3)[N:32]=[CH:31][N:30]=2)=[N:24]1.Cl>O.CS(C)=O>[CH3:22][N:23]1[CH:27]=[CH:26][C:25]([NH:28][C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[C:36]([O:39][C:40]4[CH:41]=[CH:42][C:43]([O:5][CH2:6][C@H:7]([O:9][CH:10]5[CH2:15][CH2:14][CH2:13][CH2:12][O:11]5)[CH3:8])=[CH:44][N:45]=4)[CH:37]=3)[N:32]=[CH:31][N:30]=2)=[N:24]1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 59627439(2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl methanesulfonateHCID 684298776-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol

Produkt 1

HCID 68429798N-(1-methyl-1H-pyrazol-3-yl)-6-[(5-{[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]oxy}pyridin-2-yl)oxy] quinazoline-4-amineAusbeute 75,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl methanesulfonate (214 mg, 0.90 mmol) and potassium tert-butoxide (200 mg, 1.8 mmol) were added to a dimethyl sulfoxide solution (5 ml) of 6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol (300 mg, 0.90 mmol) obtained in Example 6-3), and the reaction solution was stirred for 24 hours at 100° C. The reaction solution was cooled to room temperature, then water and aqueous 1 N hydrochloric acid solution (0.9 ml, 0.9 mmol) were added, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=99:1) to obtain N-(1-methyl-1H-pyrazol-3-yl)-6-[(5-[(2R)-2-(tetrahydro-2H-pyran-2-yloxy)propyl]oxyl pyridin-2-yl)oxy]quinazoline-4-amine (322 mg, yield: 75%) as a pale brown solid.

Aufarbeitung

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated saline water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (chloroform:methanol=99:1)

Quellen und Nachweise

ORD-Eintrag
ord-78d76566c8a14d3dba356cf569561f91
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08232284B2

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