Cesium fluoride → HCID 90118023, compound

Participants

Reaction Steps

To a 2 dram vial equipped with a stir bar was added 2,4-dichloro-6-(4-isopropoxyphenyl)pyridine (189 mg, 0.668 mmol), 5-(tributylstannyl)thiazole (250 mg, 0.668 mmol), CuI (32 mg, 0.17 mmol), CsF (304 mg, 2.00 mmol), and Pd(PPh3)4 (39 mg, 0.033 mmol). The vial was capped with a septum screw-cap and then placed under N2 atmosphere. To the vial was added degassed DMF (4 mL). The vial was placed in an 80° C. heating block with stirring for 1 hour. The vial was cooled to room temperature and then opened, and to the solution was added an additional charge of 5-(tributylstannyl)thiazole (85 mg, 0.23 mmol) and Pd(PPh3)4 (39 mg, 0.033 mmol). The vial was capped, placed under N2 atmosphere, and then placed in a 80° C. heating block with stirring for an additional 1 hour. The reaction mixture was cooled to room temperature and then transferred to a 125 mL separatory funnel. The mixture was diluted with EtOAc (50 mL) and then washed with saturated aqueous NaCl (“brine”, 50 mL). The aqueous phase was extracted with EtOAc (25 mL). The combined organics were washed with brine (25 mL); dried over MgSO4; filtered; then concentrated in vacuo to afford a dark liquid. This material was subjected to silica gel chromatography to afford 5-(4-chloro-6-(4-isopropoxyphenyl)pyridin-2-yl)thiazole as a pale orange liquid (122 mg, 55%). 1H-NMR: (400 MHz, CDCl3-d) δ 8.87 (s, 1H), 8.40 (s, 1H), 8.04-7.98 (m, 2H), 7.60 (d, J=1.5 Hz, 1H), 7.55 (d, J=1.8 Hz, 1H), 7.04-6.98 (m, 2H), 4.65 (spt, J=6.1 Hz, 1H), 1.39 (d, J=6.3 Hz, 6H); MS: MS m/z 331.1 (M++1).

Provenance & Evidence