3,5-Dibromopyridine-4-carboxaldehyde

Step 1: (0420) Diisopropylamine (2.4 g, 24.0 mmol) was dissolved in dry tetrahydrofuran (20 ml) under a nitrogen atmosphere, n-butyllithium in n-hexane (9.6 ml, 24.0 mmol) was added dropwise thereto at 0° C. followed by stirring at this temperature for 30 minutes, dry tetrahydrofuran (30 ml) was added and the mixture was cooled to −78° C., 3, 5-dibromo-pyridine 26-a (4.7 g, 20 mml) in dry tetrahydrofuran (50 ml) was added dropwise thereto followed by stirring for 30 minutes. Methyl formate (2.4 g, 40 mml) was added followed by stirring for 30 minutes, The mixture was warmed to room temperature, extracted with saturated sodium bicarbonate (100 ml) and ethyl acetate (50 ml×3). The combined organic phase was dried over anhydrous sodium sulfate, concentrated and subjected to column chromatography to give 26-b as a pale yellow solid (4.0 g, yield: 75percent). Lithium diisopropylamide (507 mmol, 1 .2 eq.) was added to 200 mL of dry THF at -78 'C under NLithium diisopropylamide (507 mmol, 1 .2 eq.) was added to 200 mL of dry THF at -78 'C under NStep 1 . 3.5-Dibromoisonicotinaldehvde Lithium di isopropylamide (507 mmol, 1 .2 eq. ) was added to 200 mL of dry THF at -78 'C under NLithium diisopropylamide (507 mmol, 1 .2 eq.) was added to 200 mL of dry THF at -78 'C under N[0187] Step 1. 3, 5-Dibromoisonicotinaldehyde. Lithium diisopropylamide (507 mmol, 1.2 eq.) was added to 200 mL of dry THF at -78 °C under N2. A solution of 3, 5-dibromopyridine (100 g, 424 mmol) in 537 mL of dry THF was then added drop-wise over 30 mm. The reaction mixture was stirred at -78 °C for 1 h. Ethyl formate (34.4 g, 465 mmol) was added drop-wise and stirred at -78 °C for 30 mm, then the reaction mixture was poured into ice-cold saturated aqueous NaHCO3 solution. The mixture was extracted with 3 x 500 mL of EtOAc. The organic layer was concentrated to provide a brown solid, which was filtered through a pad of silica gel (eluted with dichloromethane) to give the title compound as a yellow powder (70 g, 63percent).Under nitrogen protection, 150 mL anhydrous THF and 49.1 g diisopropylamine were added into a 2 L three-necked flask, and the solution was cooled to −5° C. 194 mL 2.5M n-BuLi solution was dropwise added in, and meanwhile the temperature was kept at or below 0° C., and after dropwise adding finished, the system was kept at the temperature and reacted for 1 hour, and then the solution was cooled to −70° C. 100 g 3, 5-dibromopyridine dissolved in 500 mL THF was dropwise added with keeping temperature ≦−70° C., and after the dropwise adding finished, the system was kept at the temperature and stirred for 2 hours. 61.6 g DMF dissolved in 250 mL THF was dropwise added into the resulted system with keeping temperature ≦−70° C., and stirred for 2 hours. The reaction had completed by checking by TLC. The reaction liquid was added into 2.5 L saturated sodium bicarbonate solution, extracted by ethyl acetate (800 mL×3). The organic phases were merged, washed by saturated salt water, dried by anhydrous sodiumsulfate, concentrated and recrystallized with petroleum ether to give a yellow solid, i.e. compound A2, 50 g, 45percent yield.

Molecular Weight:264.90
XLogP3:1.7
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:264.85609
Monoisotopic Mass:262.85814
Topological Polar Surface Area:30
Heavy Atom Count:10
Complexity:121
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes