Reaktion #168822

Reaktionsgleichung

hydrochloric acid

(2S)-2-(tetrahydro-2H-pyran-2-yloxy)propyl methanesulfonate

potassium tert-butoxide

6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol

→

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

Ausbeute 75.1%

Lösungsmittel

water

dimethyl sulfoxide

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction solution was cooled to room temperature
2. 2
   Extraktionextracted with ethyl acetate
3. 3
   WaschenThe organic layer was washed with saturated saline water
4. 4
   Trocknendried over anhydrous sodium sulfate
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   SonstigeThe obtained residue was purified by silica gel column chromatography (chloroform:methanol=99:1)

Vorschrift

(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]oxy}pyridin-2-yl)oxy]quinazoline-4-amine (322 mg, yield: 75%) as a pale brown solid.

Quelle