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

Temperature

110 °C

To a reaction mixture of 2-bromo-5-iodoimidazo[2,1-b][1,3,4]thiadiazole (0.150 g, 0.455 mmol), 3-methoxyphenylboronic acid (0.477 mmol) and PdCl2(Ph3P)2 (0.064 g) in dioxane (3 ml), a sat. aq. solution of K2CO3 (1 mL) was added. The 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 (1.2 eq), PdCl2(Ph3P)2 (0.2 eq) and a sat. solution of K2CO3 (1 mL) were added and heated at 100° C. for 16 h. The solvent was evaporated to dryness, and the residue was purified by automated chromatography in DCM/MeOH, 100:0 to 95:5) and then by preparative HPLC affording 5 mg of a light-yellow solid that was washed with MeOH and Et2O to obtain 2 mg of the desired product. HPLC-MS: (5-100% B in 8 min, 0.8 mL/min, 50° C.): tR=5.63 min, [M+H]+ m/z 392.1; 1H NMR (300 MHz, DMSO-d6) δ 8.86 (s, 1H), 8.41 (s, 1H), 7.80 (s, 1H), 7.53 (t, J=11.5 Hz, 3H), 7.24 (s, 1H), 6.74 (s, 2H), 3.88 (s, 3H), 3.85 (s, 1H).

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. customthe residue was purified by automated chromatography in DCM/MeOH

ORD record

ord-524d74be809841508c5239b7b65b1cfc

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815918B2