反应详情

A dry 15 mL, one neck round bottom flask was charged with 2-(5-bromopyridin-3-yloxy)acetonitrile (0.162 g, 0.762 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)acetamide (0.2021 g, 0.635 mmol), 5 mL THF and a stirbar. The flask was flushed with Ar for 2 minutes, and fitted with an inert atmosphere inlet. To the stirring solution was added tetrakis(triphenylphosphine)palladium (0.147 g, 0.127 mmol) followed by 2 M sodium carbonate (0.953 ml, 1.91 mmol). The slurry was refluxed overnight, and cooled to room temperature. The mixture was poured onto 15 mL water and extracted with DCM (3×20 mL). The DCM extracts were Loaded onto an unbuffered Varian Chem elute CE1010 (100 mL, PN 12198010). The tube was extracted with DCM (4×20 mL). The combined extracts were concentrated in vacuo, and the residue was taken up in 1 mL DCM. A precipitate formed, which was collected using a course glass filter fitted with a 0.22 μm syringe filter. The solid was dried at 60° C. at <1 mmHg for 1 h to afford N-(6-(5-(Cyanomethoxy)pyridin-3-yl)benzo[d]thiazol-2-yl)acetamide (15 mg, 7.3%). 1H NMR (300 MHz, Pyr) δ ppm 2.36 (s, 3H) 4.98 (br. s., 1H) 5.56 (s, 2H) 7.75 (dd, J=8.40, 1.90 Hz, 1H) 7.93 (dd, J=2.81, 1.86 Hz, 1H) 8.02 (dd, J=8.44, 0.48 Hz, 1H) 8.27 (dd, J=1.90, 0.44 Hz, 1H) 8.77 (d, J=2.85 Hz, 1H) 8.93 (d, J=1.83 Hz, 1H). 13C NMR (75 MHz, Pyr) δ ppm 23.71 (s, 1 C) 55.20 (s, 1 C) 116.92 (s, 1 C) 120.84 (s, 1 C) 121.15 (s, 1 C) 122.27 (s, 1 C) 126.25 (s, 1 C) 133.18 (s, 1 C) 134.41 (s, 1 C) 137.61 (s, 1 C) 138.12 (s, 1 C) 143.50 (s, 1 C) 150.53 (s, 1 C) 154.29 (s, 1 C) 160.70 (s, 1 C) 170.19 (s, 1 C). HPLC-MS: retention time=1.34 min (93.6%@215 nm; 96.7% @254 nm; m/z=325.6, calculated for C16H12N2O4S+H+=325.1).

1. customThe flask was flushed with Ar for 2 minutes
2. customfitted with an inert atmosphere inlet
3. temperatureThe slurry was refluxed overnight
4. extractionextracted with DCM (3×20 mL)
5. washelute CE1010 (100 mL, PN 12198010)
6. extractionThe tube was extracted with DCM (4×20 mL)
7. concentrationThe combined extracts were concentrated in vacuo
8. customA precipitate formed
9. customwhich was collected
10. filtrationfilter
11. customfitted with a 0.22 μm syringe
12. filtrationfilter
13. customThe solid was dried at 60° C. at <1 mmHg for 1 h