5-CYANO-2-FLUOROBENZENEBORONIC ACID

30 g (181.9 mmol) of (5-cyano-2-fluorophenyl) boronic acid, 2-chloro-4- (dibenzo [b, d] furan-4-yl) -6-phenyl-1, 3, 5-triazine(181.9 mmol), 200 mL of tetrahydrofuran and 100 mL of water are mixed and heated to 60 C. Potassium carbonate (545.6 mmol) and tetrakistriphenylphosphinepalladium (1 mmol) were added and the mixture was stirred for 3 hours under reflux.After the reaction, the reaction solution returned to room temperature was filtered to obtain a solid, and the solid was recrystallized twice with tetrahydrofuran / ethanol to obtain 53.2 g of compound 1-G (yield 83%).Under an argon atmosphere, to a 1 L, three-neck flask, 10.00 g of 2, 6-dichlorobenzonitrile, 4.79 g of F. (3S)-Methyl 3-(3-((4-bromo-5-(5-cyano-2-fluorophenyl)thiophen-3- yl)methoxy)phen l -3-c clo ro l ro anoate 10f A mixture of compound 10e (120 mg, 0.23 mmol), A mixture of compound lOe (120 mg, 0.23 mmol), A mixture of compound be (120 rng, 0.23 rnmoi), (5.-cyano-2-fluorophenyl)boronic acid(45 rng, 0.27 rnmoi), XPhos (9 mg, 0.01 mmol), K3P04 (97 mg, 0.46 rnmol) in THF (0.46rnL) was stirred for 3 h at 50 C under N. The reaction mixture was allowed to cool to RIand treated with H20 (10 mL), The resulting mixture was extracted with EtOAc (2 x 10mL). The organic layers were combined, dried over anhydrous sodium sulfate andconcentrated The resulting residue was purified by flash chromatography (0-30 %EtOAc/petroleum ether) on silica gel to obtain compound I Of as a colorless oil. Mass Spectrum (LC'IS, ESI pos.): Calcd. for C25H2jBrFNO3S: 514.0 (M-f-H); found: 513.9A mixture of 2-82 (247 mg, 1.5 mmol), 2-24 (317 mg, 1 mmol), Pd(PPh3)2C12 (70mg, 0.1 mmol), K3P04 (424 mg, 2 mmol), THF (2 mL) and H20 (0.5 mL) was degassed with N2 and stirred at 65 C overnight. The mixture was filtered and the filtrate was concentrated and purified via prep-HPLC eluting with CH3CN/H20 (with 0.5% NH4HCO3) to provide compound 1-35 (yellow solid, 161 mg, 45% yield). 'H NMR (DMSO-d6, 400 MHz): oe 8.26 (t, J 2.0 Hz, 1 H), 8.20 (dd, J, = 7.2 Hz, J2 = 2.0 Hz, 1 H), 7.97 (s, 1 H), 7.92 (d, J= 8.0 Hz, 1 H), 7.84-7.88 (m, 1 H), 7.65 (s, 1 H), 7.47-7.56 (m, 3 H), 6.15 (s, 2 H), 3.41 (dt, Ji = 6.4Hz, J2= 2.4 Hz, 2 H), 2.96 (t, J= 6.4 Hz, 2 H).Posassum carbonate (191 mg, 1.38 mmol) and (AtaPhos)2PdCI2 (33 mg, 0.046 mmol) were added underan inert atmosphere to the product of Id) (200 mg, 0.46 mmol) and 5-cyano-2-fluoro phenyl boronic acid (152.3 mg, 0.92 mmol) in a blend of t-amyl alcohol (8 mL) and water (0.8 mL). The reaction mixture was stirred for 1 h at 80C and then filtered over celite. The solvents were removed in vacuo and the rawproduct was purified first by flash column chromatography (silica gel; methanol / dichloromethane2:98) and finally by washing with diethyl ether / dichlorornethane. White solid. Yield: 102 mg (47% of theory). LC-MS (method 2): R = 2.86 mm., m/z [M+H] 472.47 (MW calc. 473.1)li-I NMR (400 MHz, DMSO-d6, oe ppm): 9.21 (s, 2H), 8.75 (s, IH), 8.37 (dd, Il-I, J = 1.6, 7.2 Hz), 8.15 (d, IH, J = 8.4 Hz), 8.09-8.05 (m, IH), 7.69 (t, lH, J = 10.0 Hz), 7.4 (d, IH, J = 8.4 Hz), 5.72 (d, IH, J =4.8 Hz), 5.26-5.22 (m, I H), 3.69-3.38 (m, 8H), 1.63 (d, 3H, J 6.4 Hz).

suzuki reaction

Molecular Weight:164.93
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:165.0397367
Monoisotopic Mass:165.0397367
Topological Polar Surface Area:64.2
Heavy Atom Count:12
Complexity:203
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes