2-Bromo-6-chloropyridin-3-amine

Uses

2-Bromo-6-chloro-3-pyridinamine is a reactant used in the synthesis of kilogram quantities of an akt Kinase inhibitor. It is mainly used as starting material for the production of many pharmaceutical compounds.

Synthesis

Step 1: Synthesis of 2-bromo-6-chloropyridin-3-amine Bromine (24.86 g, 155.57 mmol) was slowly added to a solution of acetic acid (383 mL) containing 6-chloropyridin-3-amine (20.00 g, 155.57 mmol) and sodium acetate (25.52 g, 311.14 mmol). The reaction mixture was stirred at room temperature for 1 hour. Subsequently, the acetic acid was removed by rotary evaporator. The residue was dissolved in ethyl acetate (EtOAc) and washed sequentially with saturated aqueous sodium carbonate (Na2CO3) solution, water and brine. The organic layer was dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated to afford the target product 2-bromo-6-chloropyridin-3-amine (32.20 g, 99.8% yield). Mass spectrometry analysis showed m/z = 206.96 ([M+H]+), which is consistent with the isotopic distribution pattern of Cl and Br.

References

[1] Patent: WO2012/80450, 2012, A1. Location in patent: Page/Page column 25
[2] Patent: WO2013/186335, 2013, A1. Location in patent: Page/Page column 87
[3] Patent: WO2013/186333, 2013, A1. Location in patent: Page/Page column 102
[4] Patent: WO2014/60411, 2014, A1. Location in patent: Page/Page column 56
[5] Patent: US2015/111868, 2015, A1. Location in patent: Paragraph 0856; 0857