Water → 3-Chloro-5-fluoro-2-thiazolo[5,4-c]pyridin-2-yl-benzonitrile

Temperature

150 °C

A mixture of thiazolo[5,4-c]pyridine (0.5 g, 3.67 mmol), 2-bromo-3-chloro-5-fluorobenzonitrile (1.3 g, 5.5 mmol), Pd(PPh3)4 (0.42 g, 0.36 mmol), copper(I) iodide (70 mg, 0.37 mmol) and cesium carbonate (3.9 g, 12 mmol) in dimethylformamide (15 mL) was heated at 150° C. in a microwave reactor for 5 minutes. The cooled mixture was poured into water and extracted twice with ethyl acetate. The combined organic extracts were washed with water, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by chromatography on silica (10% diethylether in DCM) to yield a pale solid (0.22 g). The reaction was repeated on the same scale, and the combined product from both reactions was purified by chromatography on silica (5% diethylether in DCM) to give the title compound as an off-white solid (0.30 g, 14%). 1H NMR (300 MHz, CDCl3): δ 9.35 (s, 1H), 8.78 (d, J=6.2 Hz, 1H), 8.10 (d, J=6.2 Hz, 1H), 7.58 (dd, J=7.8, 2.5 Hz, 1H), 7.53 (dd, J=7.4, 2.5 Hz, 1H). LCMS (Method E): RT=2.78, m/z: 290 [M+H+].

1. extractionextracted twice with ethyl acetate
2. washThe combined organic extracts were washed with water
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by chromatography on silica (10% diethylether in DCM)

ORD record

ord-85e6a1f0a541475395393b998c924eff

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697708B2