5-CYANO-3-PYRIDINYL BORONIC ACID

A 500 ml 2-neck flask was charged with 3-bromo-5-cyanopyridine (0.63 g, 2.5 mmol), 1, 1 bis (diphenylphosphino) ferrocene palladiumdichloride (0.17 g, 0.21 mmol), potassiumacetate (0.61 g, 6.21 mmol) Was dissolved in 6 mL of 1, 4-dioxane, and the mixture was heated and stirred at 90 DEG C for 21 hours. After the completion of the reaction, the reaction mixture was cooled to room temperature and filtered through celite. The filtrate was distilled under reduced pressure and dried to obtain 0.1 g of compound F (yield: 32percent).A mixture consisting of A mixture of Into a 8-mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed 7-1 (100 mg, 0.25 mmol, 1.00 equiv), dioxane (2 mL), water (0.5 mL), Into a 50-mL 3-necked round-bottom flask under nitrogen, was placed 5-3 (200 mg, 0.52 mmol, 1.00 equiv), dioxane (4 mL), water (1 mL), Compound 3-1 (120 mg, 0.30 mmol, 1 equiv), Into a 25-mL 3-necked round-bottom flask, was placed a solution of 1-5 (450 mg, 0.99 mmol, 1.00 equiv) in dioxane (6 mL), a solution of potassium carbonate (266 mg, 1.92 mmol, 2.00 equiv) in water(0.5 mL), Pd(dppf)Cl2 (71 mg, 0.10 mmol, 0.10 equiv), and (5- cyanopyridin-3-yl)boronic acid (428 mg, 2.89 mmol, 3.00 equiv) under N2. The resulting solution was stirred for 2 h at 80 C in an oil bath and then diluted with water. The resulting solution was extracted with ethyl acetate and the organic layers combined and concentrated under vacuum. Purification by flash chromatography (silica gel column with (0229) dichloromethane/methanol (30:1)) provided 100 mg (22%) of 2-1 as a white solidA solution of 5-bromo-l, 3-dimethyl-7-pyrrolidin-l-yl-pyrazolo[4, 3-b]pyridine (40 mg, 0.14 mmol), 2-ethoxy-3-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyridine (41 mg, 0.16 mmol), CS2CO3 (88 mg, 0.27) and Pd(dppf)CI2 (99 mg, 0.14 mmol) in dioxane (5 mL) and water (1 mL) was stirred at 90C for 16 hours. The reaction was concentrated .The residue was diluted with ethyl acetate (5 mL) and water (3 mL), filtered and extracted with ethyl acetate (5 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleur ethyl acetate = 10:1~1:1) followed by further purification by preparative HPLC to afford the title compound. 1H-NMR (400 MHz, Chloroform-d): delta 8.28 (d, J = 7.2 Hz, 1H), 8.17 (d, J = 5.2 Hz, 1H), 7.45 (s, 1H), 7.03 (dd, J = 7.2, 5.2 Hz, 1H), 4.46 (q, J = 7.2Hz, 2H), 4.13 (s, 3H), 3.37-3.35 (m, 4H), 2.64 (s, 3H), 2.05- 2.02 (m, 4H), 1.42 (t, 7 = 7.2 Hz, 3H). LC-MS: tR = 1.9 min (Method K), m/z = 338.1 [M+H]+.A mixture of N-[5-(7-bromo-4-oxoquinazolin-3(4H)-yl)-2-(difluoromethoxy)phenyl]-l-(4- methylpiperazin-l -yl)cyclopropane-l -carboxamide (200 mg, 365 muiotaetaomicron), A mixture of N-[5-(7-bromo-4-oxoquinazolin-3(4H)-yl)-2-(difluoromethoxy)phenyl]-l-(morpholin-4- yl)cyclopropane-l -carboxamide (120 mg, 224 muiotaetaomicron),

Molecular Weight:147.93
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:148.0444076
Monoisotopic Mass:148.0444076
Topological Polar Surface Area:77.1
Heavy Atom Count:11
Complexity:177
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes