4-Amino-2-fluorophenylboronic acid, pinacol ester

A mixture of 3-Bromo-l-methyl-lH-pyrazolo[3, 4-d]pyrimidin-4-ylamine (231 mg; 1.01 mol, 1.2 eq), 3-Fluoro-4-(4, 4, 5, 5-tetramethyl-[l , 3, 2]dioxaborolan-2-yl)-phenylamine (200 mg; 0.84 mmol, 1 eq), Pd(dppf)Cl2.DCM (138 mg; 0.17 mmol; 0.2 eq) and cesium carbonate (605 mg; 1.8 mmol; 2.2 eq) in l , 4-dioxane (4 mL) and water (1 mL) was stirred overnight at l00C under nitrogen atmosphere. The reaction mixture was then filtered through a celite pad. (0313) The filtrate was diluted with EtOAc (50 mL) and washed with 1M NaOH (2x 30 mL) and brine (2x 30 mL) .The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM:MeOH, gradient 99: 1 to 80:20) afforded the title compound (95 mg, 44%) as a brown solid. LC/MS: 259.1 [M+H]In a reaction vessel, 5-[4-chloro-3-(trifluoromethyl)phenyl]-3, 6-dihydro-2H-1, 3, 4- oxadiazin-2-one (82.0 mg, 294 muiotaetaomicronIota, Intermediate 64), 3-fluoro-4-(4, 4, 5, 5-tetramethyl- 1, 3, 2-dioxaborolan-2-yl)aniline (105 mg, 441 mumol), potassium carbonate (81.3 mg, 589 muiotaetaomicronIota) and 2-(dicyclohexylphosphino)-2', 4', 6'-triisopropylbiphenyl (8.42 mg, 17.7 muiotaetaomicronIota) were suspended in 760 muIota_ 1, 4-dioxane and 230 muIota_ water. The mixture was degassed with nitrogen for 5 min. Then, chloro(2-dicyclohexylphosphino-2', 4', 6'-triisopropyl-1, 1 '- biphenyl)[2-(2'-amino-1, 1 '-biphenyl)]palladium(ll) (6.95 mg, 8.83 muiotaetaomicronIota) was added. Nitrogen was passed through the reaction mixture. It was stirred at 80 for 2 hours in a heating block. The mixture was diluted with water and extracted with ethyl acetate three times. The combined organic layers were dried using a water-resistant filter and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMSO, filtered and purified by preparative HPLC to give 9.00 mg (95 % purity, 8 % yield) of the title compound. LC-MS (Method 2): Rt = 1.00 min; MS (ESIneg): m/z = 352 [M-H]- 1 H-NMR (400 MHz, DMSO-d6) delta [ppm]: 2.074 (0.73), 2.332 (1.24), 2.336 (0.55), 2.518 (5.59), 2.522 (3.67), 2.539 (0.67), 2.673 (1.24), 2.678 (0.55), 5.454 (16.00), 5.603 (5.98), 6.363 (1.85), 6.368 (2.13), 6.394 (1.58), 6.399 (2.43), 6.409 (2.88), 6.415 (1.70), 6.430 (2.52), 6.435 (2.09), 6.882 (1.31), 6.905 (2.31), 6.925 (1.15), 7.441 (2.40), 7.461 (2.55), 7.951 (1.70), 7.955 (1.76), 7.971 (1.49), 7.975 (1.61), 8.057 (3.49), 8.062 (3.22), 1 1.215 (5.56).General procedure: To the solution of corresponding compound 6 (0.58 mmol) in dimethoxyethane (2.0 mL) in microwave reaction vessel, were added compound 5 (0.53 mmol), Pd(PPh3)4 (0.018 g, 0.016 mmol) and aqueous 2M Na2CO3 solution (1.3 mL, 2.6 mmol). The reaction mixture was heated to 100 C by microwave irradiation with power of 100 W. After the completion of reaction was confirmed, solvent was removed in vaccuo. The residue was purified on flash column chromatography using n-hexane (Hex):EA (9:1) as an eluent to obtain compound 7.[00302] A microwave vial was charged with 5-(4-bromo-1H-pyrazol-1-yl)-1-propylpyridin-2(1H)-one (0.200 g, 0.7 mmol), Step 4: N-[3-Fluoro-4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)phenyl]-2-oxo-1-phenyl-1, 2-dihydropyridine-3-carboxamide To a mixture of

Molecular Weight:237.08
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:237.1336371
Monoisotopic Mass:237.1336371
Topological Polar Surface Area:44.5
Heavy Atom Count:17
Complexity:282
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes