Chemical Properties
Yellow Solid
Uses
2-(2-Amino-5-bromobenzoyl)pyridine is used as an intermediate in the preparation of Bromazepam.
Biological Activity
2-(2-AMINO-5-BROMOBENZOYL) PYRIDINE (2ABBP) has been shown to have anti-inflammatory properties in rat liver microsomes and cell culture experiments. The mechanism of action may involve inhibition of cyclooxygenase enzymes, which are involved in prostaglandin synthesis. 2ABBP also binds to human serum albumin and chaperones, proteins that bind other proteins or small molecules.
Synthesis
General procedure for the synthesis of 2-(2-amino-5-bromo-benzoyl)pyridine from 2-bromopyridine and 2-amino-5-bromobenzoic acid: 2-bromopyridine (173.93 g, 1101 mmol, 4.4 eq.) was slowly added to a mixture of 2.5 M n-butyllithium hexane solution (400 mL, 1000 mmol, 4 eq.) and ethyl ether (1 L) at -40 °C. 4.4 eq.). The reaction mixture was stirred at -40 °C for 1 h. A solution of 2-amino-5-bromobenzoic acid (54.14 g, 250.6 mmol, 1 eq.) in tetrahydrofuran (THF, 1 L) was added dropwise. The reaction system was slowly warmed to 0 °C and stirring was continued at this temperature for 2 hours. Subsequently, chlorotrimethylsilane (625 mL, 4924 mmol, 20 eq.) was added to quench the reaction. The mixture was stirred at room temperature for 30 minutes, then cooled to 0 °C and quenched with 3N hydrochloric acid (625 mL). The aqueous layer was separated and the organic layer was extracted once with 3N hydrochloric acid. The combined aqueous phases were neutralized with solid sodium hydroxide pellets while cooling in an ice bath. The neutralized aqueous phase was extracted with ether (3 x 1L). The combined ether extracts were dried with anhydrous sodium sulfate, filtered and concentrated to give a black oil. The crude product was purified by fast chromatography (silica gel column, 1 L, eluent 20-30% ethyl acetate/hexane) to afford the target compound 2-(2-amino-5-bromo-benzoyl)pyridine as a brown solid (62 g, 224 mmol, 89.3% yield).
References
[1] Patent: EP1183243, 2006, B1. Location in patent: Page/Page column 11
[2] Patent: WO2014/154762, 2014, A1. Location in patent: Page/Page column 62
[3] Patent: US2014/296230, 2014, A1. Location in patent: Paragraph 0303-0306
[4] Patent: CN108264499, 2018, A. Location in patent: Paragraph 0050-0051; 0075; 0076; 0077-0079
