Cesium carbonate → Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-(2,2-dimethylpropoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate

Temperature

110 °C

To a stirred solution of Intermediate 6 (1.60 g, 4.209 mmol) in anhydrous N,N-dimethylformamide (10 mL) was added cesium carbonate (2.74 g, 8.418 mmol) followed by 1-bromo-2,2-dimethylpropane (1.60 mL, 12.629 mmol) at room temperature. The resulting suspension was stirred at 110° C. overnight under nitrogen atmosphere. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (200 mL) and water (100 mL). The layers were separated. Aqueous layer was extracted with ethyl acetate (2×50 mL) and the combined organic layers were washed with brine (2×50 mL), dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure. The residue obtained after the evaporation of the solvent was purified by silica gel column chromatography using 10% ethyl acetate in petroleum ether to obtain 1.20 g of the product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 1.07 (s, 9H), 1.39 (t, J=6.9 Hz, 3H), 3.57 (s, 2H), 4.35-4.42 (m, 2H), 7.18 (t, J=74.7 Hz, 1H), 7.20-7.25 (m, 2H), 7.47 (d, J=3.9 Hz, 1H), 7.52-7.58 (m, 1H), 7.73 (d, J=16.2 Hz, 1H), 7.90 (d, J=16.2 Hz, 1H), 8.10-8.16 (m, 1H); APCI-MS (m/z) 451.10 (MH)+.

1. temperatureThe reaction mixture was cooled to room temperature
2. customThe layers were separated
3. extractionAqueous layer was extracted with ethyl acetate (2×50 mL)
4. washthe combined organic layers were washed with brine (2×50 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationThe filtrate was concentrated under reduced pressure
8. customThe residue obtained
9. customafter the evaporation of the solvent
10. customwas purified by silica gel column chromatography

ORD record

ord-a9ff8a4d49a94ccdb89c33a614935186

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318928B2