90% |
With dmap; In dimethyl sulfoxide; at 80℃; for 3h; |
A mixture of <strong>[13790-39-1]4-chloro-6,7-dimethoxyquinazoline</strong> (0.63 g, 2.80 mmol), 6- chloropyridin-3-oi (0.37 g, 2.84 mol), and DMAP (0.35 g, 2.84 mmol) in DMSO (3 mL) was stirred at 80 C for 3 h. The reaction mixture was then cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was separated and dried over sodium sulfate. The diying agent was filtered off, and the filtrate concentrated under reduced pressure to give a residue, which was purified by chromatography (ethyl acetate/hexanes = 6/4) to provide 4-((6-chloropyridin-3-yl)oxy)-6,7-dimethoxyquinazoline as a white solid (0.8 g,90%). fH NMR (DMSO-de, 300 MHz) 8 57 (s, 1H), 8.50 (d, ./= 3.0 Hz, 1H), 7.95 (dd, J= 8.7, 3.0 Hz, 1H), 7 67 (d, ,/ = 8.7 Hz, 1 1 1). 7 57 (s, 1 1 1). 7.40 (s, 1 1 1). 3.98 (s, 3H), 3.97 (s, 3H) ppm; MS m/e 318.1 (M i l) |
83% |
|
Potassium t-butoxide (1 mL, 1 mmol, 1 M in THF) was added to 2-chloro-5-hydroxypyridine (198 mg, 1.5 mmol) under inert atmosphere. The reaction mixture was stirred at room temperature for 15 min, then a solution of 6,7-dimethoxy-4-chloroquinozoline (225 mg, 1 mmol) in DMSO (1 mL) was added. The resulting solution was heated to 75 C for 2 h. The reaction mixture was quenched with H20 (50 mL) and EtOAc (2 x 50 mL) was added to extract the aqueous solution. The combined organic layers were dried over Na2S04 then concentrated under vacuum. The residue was purified by flash chromatography (eluting with 60-(at)70% EtOAc in hexanes) to give 4-[(6-chloropyridin-3-yl)oxy]-6,7-dimethoxyquinazoline (264 mg; 0.83 mmol; 83% yield) ; MS (APCI) (M+H)+ 318. 1H NMR (400 MHz, CHLOROFORM-D) 6 ppm 4.04 (s, 3 H) 4.05 (s, 3 H) 7.42 (d, (at)8.6 Az, 1 H) 7.48 (s, 1 H) 7.63 (dd, J=8.6, 3.0 Hz, 1 H) 8.38 (d, JL2.8 Hz, 1 H) 8.57 (s, 1 H). |
9.1g |
With dmap; In dimethyl sulfoxide; at 20 - 80℃; for 2h;Inert atmosphere; |
Under the argon, the DMAP (4.4g) added to the 4-chloro -6,7-dimethoxyquinazoline (8.0g) and 6-chloro-pyridine-3-ol (4.6g) of suspension in DMSO (20 ml), the bath temperature (80 C) heating and stirring 2 hours, at room temperature and to a cup. Later, the reaction solution is diluted with ethyl acetate, and washing water and saturated sodium bicarbonate aqueous solution. The organic layer is dried with anhydrous sodium sulfate and concentrated. The resulting residue with hexane-ethyl acetate (3:1) washing, to obtain the title compound (9.1g), which has the following physical property value. |