4-(3-Pyridyl)-2-chloropyrimidine

In a 250 mL three-necked flask, 2, 4-dichloropyrimidine (5.0 g, 33.56 mmol)Dissolved in 1, 4-dioxaneAnd water (4: 1, 50 mL) A solution of 3-boronic acid pyridine (4.95 g, 40.27 mmol), Potassium carbonate (9.28 g, 67.12 mmol)And Pd (dppf) Cl2 (2.45 g, 3.36 mmol);The system was replaced with argon three times, Gradually heated to 90 ° C, Reaction for 4 hours;After the reaction, the system was concentrated under reduced pressure to remove most of the solvent, Ethyl acetate (150 mL)And water (100 mL), Extraction and separation, The aqueous phase was then extracted with ethyl acetate (80 mL)The organic phases were combined, Re-water (80 mL x 2) and saturateWashed with brine (80 mL x 2)Liquid separation, The organic phase was dried over anhydrous sodium sulfate for 3 hours, Filtration and concentration, Crude;The crude product was added petroleum ether (32 mL)And ethyl acetate (6 mL) were stirred for 1 hour, filter, Dried in vacuo to give 4.8 g of 2-chloro-4- (3-pyridyl) pyrimidine, The yield was 74.6percentPurity HPLC was greater than 95percent.Preparation of 2-chloro-4-(pyridin-3-yl)pyrimidine[00106] Into a 500-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen were placed a solution of pyridin-3-ylboronic acid (4.42 g, 36.0 mmol, 1.00 equiv) in THF/HGeneral procedure: To a solution of 2, 4-dichloro-5-methylpyrimidine (500 mg, 3.1 mmol) and 4-trifluoromethoxylphenylboronic acid (644 mg, 3.1 mmol) in dioxane (15 mL), Pd(PPhPreparation of 2-chloro-4-pyridin-3-yl-pyrimidine lll-a To a solution of n-butyllithium (2.5 molar in hexane, 13.5 mL, 34 mmol) in anhydrous diethylether (50 mL) under argon at -78 ' was added 3-bromo pyridine (3 mL, 31 mmol). The mixture was stirred for 1 h, then a suspension of 2-chloro pyrimidine (3.6 g, 31 mmol) in anhydrous diethylether (30 mL) was added portionwise over 10 min. The resulting mixture was stirred at -30 °C for 30 min, and then allowed to warm to 0 °C for 1 h, at which point the reaction was successively quenched by addition of water (1 mL) in THF (10 mL) and DDQ (7.6 g, 34 mmol) in THF (25 mL). The resulting brown suspension was stirred at room temperature for 15 min, then cooled to 0 ', and treated with hexane (25 mL) and aqueous NaOH (3N, 25 mL). The mixture was stirred at 0 ' for 5 min, diluted with water (100 mL) and then extracted with ethyl acetate. The combined organic layers were washed with water, dried on MgS0(2) Feeding: Weigh 2-oxo-4- (3-pyridyl) - pyrimidine and 1.73g thionyl chloride 20.0ml into the reaction flask and catalyst DMF770μL, system reaction 6h after TLC monitoring material point at 70 disappeared, the reaction was completed.Post-treatment: the system to be cooled, the system was poured into 400ml of ice water, adjusted to pH 8 with sodium hydroxide solution, (30ml × 3) and extracted with ethyl acetate, the extract was dried over anhydrous sodium sulfate, suction filtered, the The filtrate was evaporated to dryness to give a pale yellow solid, yield 65percent.2.

Molecular Weight:191.62
XLogP3:1.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:191.0250249
Monoisotopic Mass:191.0250249
Topological Polar Surface Area:38.7
Heavy Atom Count:13
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes