6-BROMO-1H-BENZOIMIDAZOLE-4-CARBOXYLIC ACID

To 2, 3-diamino-5-bromobenzoic acid ethyl ester (478 mg, 2 mmol) 4M diluted hydrochloric acid (6 ml) was added to a mixture with formic acid (6 mmol). The reaction was refluxed overnight. The reaction solution was spun to a solid.To To a solution of Example 35 -((3-carbamoyl-7-(2, 4-dimethoxypyrimidin-5-yl)quinolin-4-yl)amino)-1-ethyl-1 H- benzordlimidazole-7-carboxylic acid ethyl 5-bromo-1 -ethyl-1 H-benzo[dlimidazole-7-carboxylate. To a mixture of 6- bromo-1 H-benzo[d]imidazole-4-carboxylic acid (200 mg, 0.830 mmol) in N, N- dimethylformamide (4 mL) were added cesium carbonate (1 190 mg, 3.65 mmol) and ethyl iodide (0.148 mL, 1 .825 mmol). The flask was equipped with a nitrogen balloon and the reaction mixture was heated to 50 C. After 30 minutes, LCMS indicated that no starting material remained and ~1 :1 mixture of regioisomers was present. The reaction mixture was allowed to cool to room temperature and diluted with water (40 mL; no precipitation observed) and ethyl acetate (50 mL). The ethyl acetate layer was dried over Na2S04, filtered and concentrated under reduced pressure. The crude residue was purified by reverse phase HPLC (ODS, 10-90% acetonitrile/water + 0.1 % trifluoroacetic acid). Appropriate fractions for the first peak to elute were combined, adjusted to pH ~7 and extracted with ethyl acetate twice. The combined extracts were dried over Na2S04, filtered and concentrated under reduced pressure to provide ethyl 6-bromo-1-ethyl-1 H- benzo[d]imidazole-4-carboxylate (89 mg, 0.300 mmol, 36.1 % yield) as a white solid. LCMS (ES+) m/e 297 [M+H]+. The work-up procedure described above was repeated with the second product to elute to provide ethyl 5-bromo-1 -ethyl- 1 H-benzo[d]imidazole-7-carboxylate (109 mg, 0.367 mmol, 44.2 % yield) as a pale yellow solid. LCMS (ES+) m/e 297 [M+H]+.

Molecular Weight:241.04
XLogP3:1.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:239.95344
Monoisotopic Mass:239.95344
Topological Polar Surface Area:66
Heavy Atom Count:13
Complexity:224
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes