2-Methylpyridine-3-boronic acid pinacol ester

A mixture of ethyl 8-bromo-5-(((5-fluorobenzofuran-4-yl)methyl)amino)imidazo[l, 2- c]pyrimidine-2-carboxylate (120 mg, 274 miho, 1.00 equiv), 2-m ethyl-3 -(4, 4, 5, 5-tetramethyl- 1, 3, 2-dioxaborolan-2-yl)pyridine (120 mg, 548 pmol, 2.00 equiv), sodium bicarbonate (69.0 mg, 822 pmol, 32.0 pL, 3.00 equiv) and Pd(dppf)Cl2 (22.4 mg, 27.4 pmol, 0.100 equiv) in dioxane (3.00 mL) and water (0.600 mL) was purged with nitrogen and stirred at 105 C for 1 h under a nitrogen atmosphere. The mixture was concentrated at reduced pressure to give a residue. The crude material was purified by prep-TLC (DCM / Methyl alcohol = 20 / 1) to afford ethyl 5-(((5-fluorobenzofuran-4-yl)methyl)amino)-8-(2-methylpyridin-3-yl)imidazo[l, 2- c]pyrimidine-2-carboxylate (100 mg, 78.9% yield, 96.3% purity) as a brown solid. LCMS [M+l]: 446.2.To a solution of ethyl 8-bromo-5-(((5-fluoro-2, 3-dihydrobenzofuran-4- yl)methyl)amino)imidazo[l, 2-c]pyrimidine-2-carboxylate (50.0 mg, 115 miho, 1.00 equiv), 2- methyl-3-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyridine (37.8 mg, 172 pmol, 1.50 equiv) in dioxane (3.00 mL) was added water (1.00 mL) followed by Pd(dppf)Cl2 (8.41 mg, 11.5 pmol, 0.100 equiv) and sodium bicarbonate (29.0 mg, 345 pmol, 3.00 equiv). The reaction mixture was stirred at 105 C for 1 h under nitrogen. The mixture was cooled to 25 C and filtered. The filtrate was concentrated in vacuo to provide a residue. The crude material was purified by prep-TLC (dichloromethane/methanol = 10/1) to afford ethyl 5-(((5-fluoro-2, 3- dihydrobenzofuran-4-yl)methyl)amino)-8-(2-methylpyridin-3-yl)imidazo[l, 2-c]pyrimidine-2- carboxylate (40.0 mg, 75.0% yield, 96.4% purity) as a brown solid.A solution of tot-butyl (4i?)-2-(5-(4-bromophenyl)-5-methyl-4-oxo-4, 5- dihydro-lH-imidazol-2-yl)-4-hydroxypyrrolidine-l-carboxylate (Intermediate 4, 200 mg, 0.460 mmol), 2-methyl-3-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyridine (120 mg, 0.548 mmol), PdCl2(dppf) (66.8 mg, 0.0913 mmol) and Na2C03 (145 mg, 1.37 mmol) in dioxane (10 mL) and water (1.5 mL) was stirred at 80C for 1 hour in microwave. The mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (gradient: 0%-10% MeOH/DCM) to yield 150 mg (73%) of the title compound as a light yellow solid. LCMS (ESI): RT (min) = 0.860, [M+H]+ = 451, method = J.General procedure: Under inert atmosphere, a mixture of halide F, Fl or F2 (1 0 equivj, boronic acid derivative G(1.5 equiv.) and PdCI2(dppf).CH2CI2 (010 equiv.) in a mixture of DMF or DMA (0.10 moLL1)and aqueous K2C03 (1.2 moW1) was heated at 110C for 16 hours. After cooling, the reactionmixture was hydrolysed and extracted twice with EtOAc, The organic layers were combined, washed with brine, dried over MgSO4, concentrated and purified to afford the product.General procedure: Under inert atmosphere, XPhos precatalyst (0.05 equiv.) was added to a mixture of haNde F, Fl or F2 (1, 0 equiv, ), boronic acid derivative 0 (1.5 equiv, ) and tripotassium phosphate (2.0 equiv.) in dioxane (0.15 moLLj and water (1.0 moLL'1). The reaction mixture was heated at 80C for 2 hours. After cooling, the reaction mixture was hydrolysed and extracted twice with EtOAc. The organic layers were combined, washed with brine, dried over MgSO4, concentrated and purified to afford the product.General procedure: Under inert atmosphere, XPhos precatalyst (0.05 equiv.) was added to a mixture of haNde F, Fl or F2 (1, 0 equiv, ), boronic acid derivative 0 (1.5 equiv, ) and tripotassium phosphate (2.0 equiv.) in dioxane (0.15 moLLj and water (1.0 moLL'1). The reaction mixture was heated at 80C for 2 hours. After cooling, the reaction mixture was hydrolysed and extracted twice with EtOAc. The organic layers were combined, washed with brine, dried over MgSO4, concentrated and purified to afford the product.General procedure: Under inert atmosphere, XPhos precatalyst (0.05 equiv.) was added to a mixture of haNde F, Fl or F2 (1, 0 equiv, ), boronic acid derivative 0 (1.5 equiv, ) and tripotassium phosphate (2.0 equiv.) in dioxane (0.15 moLLj and water (1.0 moLL'1). The reaction mixture was heated at 80C for 2 hours. After cooling, the reaction mixture was hydrolysed and extracted twice with EtOAc. The organic layers were combined, washed with brine, dried over MgSO4, concentrated and purified to afford the product.General procedure: Under inert atmosphere, XPhos precatalyst (0.05 equiv.) was added to a mixture of haNde F, Fl or F2 (1, 0 equiv, ), boronic acid derivative 0 (1.5 equiv, ) and tripotassium phosphate (2.0 equiv.) in dioxane (0.15 moLLj and water (1.0 moLL'1). The reaction mixture was heated at 80C for 2 hours. After cooling, the reaction mixture was hydrolysed and extracted twice with EtOAc. The organic layers were combined, washed with brine, dried over MgSO4, concentrated and purified to afford the product.

Molecular Weight:219.09
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:219.1430590
Monoisotopic Mass:219.1430590
Topological Polar Surface Area:31.4
Heavy Atom Count:16
Complexity:252
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes