Sodium Carbonate → 5-[2-(4-Methoxy-phenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-trifluoromethyl-pyridin-2-ylamine

Temperature

110 °C

To a mixture of 2-bromo-5-iodoimidazo[2,1-b][1,3,4]thiadiazole (0.150 g, 0.455 mmol), 3-cyanophenylboronic acid (0.477 mmol) and PdCl2(Ph3P)2 (0.064 g) in dioxane (3 mL), an aq. solution of Na2CO3(2 M, 0.9 mL) was added. The reaction mixture was heated at 110° C. for 24 h in a sealed tube. The solvent was evaporated, the residue precipitated with water, and after drying the resulting gum was washed with Et2O. The residue was suspended in dioxane (3 mL), and 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3-trifluoromethyl-pyridin-2-ylamine (1.05 eq), PdCl2(Ph3P)2 (0.2 eq) and a sat. solution of K2CO3 (0.9 mL) were added and heated at 100° C. for 16 h. The solvent was evaporated to dryness. The residue was washed with water, followed by ethyl ether. The resulting precipitate was washed with DCM followed by MeOH and purified by preparative HPLC to afford the desired product (0.010 g). HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=5.57 min, [M+H]+ m/z 392.1; 1H NMR (300 MHz, DMSO-d6) δ=8.85 (d, J=1.6 Hz, 1H), 8.36 (d, J=1.9 Hz, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.75 (s, 1H), 7.16 (d, J=8.9 Hz, 2H), 6.72 (s, 2H), 3.86 (s, 3H) ppm.

1. customThe solvent was evaporated
2. customthe residue precipitated with water
3. customafter drying the resulting gum
4. washwas washed with Et2O
5. temperatureheated at 100° C. for 16 h
6. customThe solvent was evaporated to dryness
7. washThe residue was washed with water
8. washThe resulting precipitate was washed with DCM
9. custompurified by preparative HPLC

ORD record

ord-5bc0ef1f9e5f462881dcf886e4a8dc8c

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815918B2