Yield:52121-34-3 98%

Reaction Conditions:

with sulfuric acid;bromine;silver sulphate in lithium hydroxide monohydrate at 20;

Steps:

27.a 2- bromo-1 -ethyl-4-nitrobenzene

Example 27 3-((3-carbamoyl-7-(2,4-dimethoxypyrimidin-5-yl)-6-ethylquinolin-4-yl)amino)-5- cvclopentylbenzoic acid 2- bromo-1 -ethyl-4-nitrobenzene. To a mixture of 1 -ethyl-4-nitrobenzene (4.0 g, 26.4 mmol), silver sulfate (8.18 g, 26.4 mmol), concentrated sulphuric acid (24 mL) and water (2.8 mL), was added bromine (4.23 g, 26.4 mmol) dropwise at ambient temperature. After the addition, the mixture was stirred for 4 h at ambient temperature, then poured into dilute sodium hydrogen sulfite solution (10%, 150 mL) and extracted with ethyl acetate (300 mL x 3). The extracts were dried over Na₂S0₄. The solvent was concentrated under vacuum to provide the title compound (5.95 g, 98%). ¹H NMR (300 MHz, DMSO-d₆) ppm 1.20 (t, J=7.5 Hz, 3 H), 2.82 (q, J=7.5 Hz, 2 H), 7.65 (d, J=8.4 Hz, 1 H), 8.19 (dd, J=2.4, 8.4 Hz, 1 H), 8.38 (d, J=2.4 Hz, 1 H).

References:

WO2013/96151,2013,A1 Location in patent:Page/Page column 91