* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Step A: Preparation of 5-bromo-2-phenoxypyrimidine A mixture consisting of 5-bromo-2-iodopyrimidine (Bridge Organics, 1.01 g, 3.57 mmol), phenol (Aldrich, 3.35 g, 35.7 mmol), and potassium carbonate (Aldrich, 4.93 g, 35.7 mmol) was stirred neat at 165° C. under a nitrogen atmosphere for four hours. After cooling to room temperature, the mixture was partitioned between ethyl acetate (250 mL) and 1 N hydrochloric acid (4*200 mL). The organic layer was washed with 1 N hydrochloric acid until disappearance of color in the aqueous layer. The phases were separated and the organic phase was washed with water (100 mL) and brine (100 mL). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to provide an orange oil (1.1 g). The product was purified by flash silica column chromatography. Elution through an 80-g Silicycle.(R). flash silica cartridge with 10percent ethyl acetate in hexanes afforded the title compound as a white solid (0.82 g, 92percent yield); Rf 0.51 with 8:2 v/v hexanes-ethyl acetate; 1H-NMR (400 MHz; CDCl3) δ 8.56 (s, 2H), 7.46-7.41 (m, 2H), 7.30-7.24 (m, 1H), 7.20-7.16 (m, 2H); MS (APCI+) m/z 252.9 (M+1).
87%
With 2-Picolinic acid; potassium phosphate; copper(l) iodide In dimethyl sulfoxide at 100℃; for 20 h; Inert atmosphere
Procedure: 5-bromo-2-iodopyrimidine (3 mmol), phenol (3.2 mmol), 2-picolinic acid (0.3 mmol), cuprous iodide CuI (0.3 mmol), potassium phosphate (4.5 mmol) was placed in 25 mL dry In a flask, 15 mL of DMSO was added and the mixture was heated to 100° C. under Ar protection. After about 20 hours of reaction, TLC conversion was complete. After the mixture was cooled to room temperature, a large amount of ethyl acetate was added, washed with water four times and extracted twice with ethyl acetate. The EA phases were combined and washed with saturated brine. The organic phase was dried, filtered, evaporated to dryness and purified by silica gel column chromatography to give 1.1 g of a white product. , Yield 87percent
Reference：
[1] Patent: US2010/75990, 2010, A1, . Location in patent: Page/Page column 40
[2] Patent: CN108069974, 2018, A, . Location in patent: Paragraph 0194-0196
2
[ 98-80-6 ]
[ 257280-25-4 ]
Yield
Reaction Conditions
Operation in experiment
70%
With oxygen; caesium carbonate In 1,2-dimethoxyethane at 20℃; for 10 h;
Example 40 5-Bromo-2-phenoxypyrimidine 3-(5-Bromo-pyrimidin-2-yloxy)-3H-[1,2,3]triazolo[4,5-b]pyridine (100 mg, 0.34 mmole) was dissolved in DME (4 mL) at RT and phenyl boronic acid (125 mg, 1.02 mmole) was added to it. Cs2CO3 (443 mg, 1.36 mmole) and Pd(PPh3)4 (39 mg, 0.03 mmole) was added to the reaction mixture and purged with O2. The reaction mixture was then stirred at RT for 10 h and was directly purified by flash chromatography to afford a white solid (60 mg, 70percent). 1H-NMR (CDCl3, 300 MHz) δ (ppm) 8.57 (s, 2H), 7.44 (m, 2H), 7.26 (m, 1H), 7.17 (d, 2H, J=4.2 Hz). LCMS (ES-MS) [(M+H)+]: for C10H7BrN2O 251.07, found 251.30.
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