4,6-DIBROMOPYRIMIDINE

0.95 g (4 mmol) of 4, 6-bromopyrimidine was placed in a 100 ml four-necked flask equipped with a reflux tube and a thermometer.1.26 g (8 mmol) of 2-chloropyridine-5-boronic acid, Toluene (30 ml), ethanol (15 ml), Add 2M potassium carbonate aqueous solution (30ml)Nitrogen bubbling was performed for 1 hour. Thereafter, 0.23 g (1.25 mmol) of tetrakis (triphenylphosphine) palladium (0) was added, and the mixture was reacted under reflux for 10 hours.TLC confirmed the disappearance of the raw material and the spots which seemed to be the scavenging compounds. After suction filtration, Extract with chloroform, water 150 ml x 1 time, Washed twice with 150 ml of brine. After dehydration with magnesium sulfate, Concentration by evaporation gave an orange solid.Next, the origin was removed using a glass filter.About 200cc of silica gel (height 10cm)Chloroform was used as the injection solvent, and heated hexane: ethyl acetate = 10: 4 solvent was used as the developing solvent.After concentration by evaporation, the dispersion was washed twice with hexane, dried under reduced pressure, 1.04 g (43% yield) of a yellow-white solid was obtained.To a stirred solution of Under a nitrogen atmosphere, 4g of [0489] Step 1: Synthesis of methyl 4-(6-bromopyrimidin-4-yl)-3-chlorobenzoate. To a stirred solution of 35.7g in a dry 2L three-necked flask 4.6-dibromopyrimidine and 27.9 g 3-aminobiphenyl, Then dry and degassed 800 mL of toluene was added as a solvent. Add 43.2g of sodium tert-butoxide, 0.67g catalyst palladium acetate (2% mol) and 3.7g Ligand 1, 1'-binaphthyl-2, 2'-bisdiphenylphosphine (BINAP, 4% mol). The temperature was raised to 110C and the reaction ended overnight. Cool to room temperature, add activated carbon adsorption, suction filtration, remove solvent, Recrystallization from toluene and ethanol, 33.3 g of intermediate K was obtained (yield 68%). (300 mg) and 1-cyclopropylmethanamine (130 p1) were stirred in dioxane 1, 4-dioxane (6.0 ml) for 2h at 110'C. The mixture was then concentrated under reduced pressure. The crude was solubilised in DCM and water was added. The aqueous phase was extracted two times with EtOAc. The organic phase was dried (silicone filter) andconcentrated under reduced pressure. The crude was used without further purification.LC-MS (Method 2): Rt 0.99 mm; MS (ESIpos): mlz = 228 [M+H]