96938-51-1

1824-81-3

532-55-8

96938-51-1

To a solution of benzoyl isothiocyanate (83.0 g, 509.3 mmol) in acetone (700 mL) was slowly added a solution of 6-methylpyridin-2-amine (50 g, 463.0 mmol) in acetone (600 mL) dropwise. The reaction mixture was heated to reflux and stirred for 3 hours. Upon completion of the reaction, the mixture was decanted onto crushed ice, and the resulting precipitate was filtered and washed sequentially with water, water/methanol (1:1), and methanol to afford 1-benzoyl-3-(6-methylpyridin-2-yl)thiourea as a yellow solid (100.1 g, 80% yield). 1-Benzoyl-3-(6-methylpyridin-2-yl)thiourea (60 g, 221.4 mmol) was dissolved in THF (1000 mL), 2N NaOH solution (243.5 mL) was added and heated to reflux for 3 hours. After cooling to room temperature and filtering, (6-methylpyridin-2-yl)thiourea was obtained as a white solid (34.1 g, 92% yield). (6-Methylpyridin-2-yl)thiourea (13.2 g, 79.16 mmol) was mixed with 2-bromo-1-(4-bromophenyl)ethan-1-one (22 g, 79.16 mmol) in ethanol (300 mL) and heated to reflux and stirred for 3 hours. The reaction solution was concentrated and purified by silica gel column chromatography to afford N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-6-methylpyridin-2-amine as a yellow solid (14.3 g, 53% yield). N-[4-(4-bromophenyl)-1,3-thiazol-2-yl]-6-methylpyridin-2-amine (5 g, 14.5 mmol), bis(pinacolato)diboron (4.8 g, 18.8 mmol), Pd(dppf)2Cl2 (1.2 mg, 1.5 mmol) and AcOK (4.3 g, 43.3 mmol) were dissolved in dioxane ( 100 mL) and heated to 80 °C for overnight reaction. Evaporation of the solvent gave 6-methyl-N-{4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3-thiazol-2-yl}pyridin-2-amine. The coupling reaction with 2-dimethylamino-4-bromopyridine (200 mg) was carried out under standard conditions to give 33 mg as a yellow solid (17% yield).