2-(2-Amino-5-bromobenzoyl)pyridine

To a -40°C solution of 2.5 M n-butyllithium in hexane (400 mL, 1000 mmol, 4 eq) and diethyl ether (1 L) was added 2-bromopyridine (173.93 g, 1101 mmol, 4.4 eq) over approximately 30 min. The reaction was stirred for 1 h at -40°C, and then treated with 5-bromoanthranilic acid (54.14 g, 250.6 mmol, 1 eq) in THF (1 L). The reaction was warmed to 0°C and stirred 2 h at 0°C, then quenched with chlorotrimethylsilane (625 mL, 4924 mmol, 20 eq). The reaction was stirred 30 min at ambient temperature, then cooled to 0°C and quenched with 3N HCI (625 mL). The aqueous layer was separated, and the organic layer was extracted once with 3N HCl. The combined aqueous layers were neutralized with solid sodium hydroxide pellets, with cooling via ice bath. The resulting mixture was extracted with diethyl ether (3 .x. 1 L). The combined ether layers were dried over sodium sulfate, filtered and concentrated to a black oil, which was subsequently purified by flash chromatography (1 L silica gel, 20-30percent ethyl acetate/hexane) to give the required compound as a brown solid (62 g, 224 mmol, 89.3percent).To a -40 °C solution of 2.5 M n-BuLi (18 mL) in THF (300 mL) is added 2- bromopyridine (5.0 g, 32 mmol) over 15 min. The reaction is stirred for 1 h at -40 °C, and then treated with 2-Amino-5-bromo-benzoic acid (6.9 g, 32 mmol) in THF (300 mL). The reaction is warmed to 0 °C and stirred for 2 h then quenched with TMSC1 (3.4 g, 32 mmol). The reaction is stirred at room temperature for 30 min then cooled to 0 °C and quenched with 3M HCl (20 mL). The aqueous layer is separated and the organic layer is extracted with 3M HCl. The organic layer is basified with solid NaOH, the resulting mixture is extracted with EtOAc, and the organic layer is dried over NaTo a -40° C. solution of 2.5 M n-BuLi (18 mL) in THF (300 mL) is added 2-bromopyridine (5.0 g, 32 mmol) over 15 min. The reaction is stirred for 1 h at -40° C., and then treated with 2-Amino-5-bromo-benzoic acid (6.9 g, 32 mmol) in THF (300 mL). The reaction is warmed to 0° C. and stirred for 2 h then quenched with TMSCl (3.4 g, 32 mmol). The reaction is stirred at room temperature for 30 min then cooled to 0° C. and quenched with 3M HCl (20 mL). The aqueous layer is separated and the organic layer is extracted with 3M HCl. The organic layer is basified with solid NaOH, the resulting mixture is extracted with EtOAc, and the organic layer is dried over NaAdd tetrahydrofuran (44 mL) to the reaction flask, protect with nitrogen, add n-butyl lithium (51 mL) at -40 ° C, control the internal temperature not to exceed -20 ° C, lower the temperature to -40 ° C, and slowly add 2-bromopyridine ( 15.8g), the reaction was incubated for 1 hour, the temperature was controlled below -40 ° C, and a solution of 2-amino-5-bromo-benzoic acid (6.7 g) dissolved in (44 mL) tetrahydrofuran was added dropwise.After the dropwise addition, the temperature was naturally raised to about 0 ° C for 3 hours.The internal temperature was kept below 10 °C, and a saturated ammonium chloride solution (11 mL) was slowly added dropwise to terminate the reaction. Water (50 mL) was added thereto, and the mixture was partitioned. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (50mL) The organic layers were combined and washed with saturated aqueous sodium chloride (40 mL×2).Drying over anhydrous sodium sulfate, filtration, and concentrated under reduced pressure to give an oily substance, purified by column chromatography (eluent PE: EA = 3:1 to 1:1, volume ratio), and the positive component was collected and concentrated to give a solid product ( 4.37 g, yield 50.7percent).(2-Amino-5-bromo-phenyl)-pyridin-2-yl-methanone 123; The anion of 2-bromo-pyridine 121 and 2-amino-5-bromobenzoic acid 122 were condensed to provide the 2'-pyridylketone 123.

Intermediate in the preparation of Bromazepam.

Molecular Weight:277.12
XLogP3:3.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:275.98983
Monoisotopic Mass:275.98983
Topological Polar Surface Area:56
Heavy Atom Count:16
Complexity:259
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes