5-CHLORO-3-PYRIDINEBORONIC ACID

A mixture of A mixture of A mixture of N-[5-(7-bromo-6-fluoro-4-oxoquinazolin-3(4H)-yl)-2-(trifluoromethoxy)phenyl]-l-(4- methylpiperazin-l -yl)cyclopropane-l -carboxamide (850 mg, 1.45 mmol), A mixture of N-[5-(7-bromo-6-fluoro-4-oxoquinazolin-3(4H)-yl)-2-(trifluoromethoxy)phenyl]-l - (morpholin-4-yl)cyclopropane-l-carboxamide (20.0 mg, 35.0 mumol), A mixture of N-[5-(7-bromo-8-fluoro-4-oxoquinazolin-3(4H)-yl)-2-(trifluoromethoxy)phenyl]-l - (morpholin-4-yl)cyclopropane-l -carboxamide (70.0 mg, 123 muiotaetaomicron), A mixture of N-[5-(7-bromo-4-oxoquinazolin-3(4H)-yl)-2-(difluoromethoxy)phenyl]-l-(4- methylpiperazin-l -yl)cyclopropane-l -carboxamide (65.0 mg, 119 muiotaetaomicron), General procedure: To a solu of 14 (60 mg, 0.14 mmol) in DMF (2 mL) was added selected aryl boronic acid (0.22 mmol) and 2 M Na2CO3 (0.2 mL). The reaction mixture was degassed with bubbling N2 (g) for 10 mins. Added PdCl2(dppf) (10 mg, 0.013 mmol), heated to 60 C and stirred for 10-30 mins. The reaction was cooled to room temperature, diluted with 5% LiCl (aq. Solu., 16 mL) and extracted with EtOAc (2 x 10 mL). The combined organic extracts were washed with 5% LiCl (aq. Solu., 2 x 15 mL) and brine (20 mL), dried over Na2SO4, passed through a plug of celite and concentrated under vacuum. The residue was purified by column chromatography using 0 to 100% EtOAc in hexanes then 0 to 10% MeOH in EtOAc to afford the desired product:To a mixture of potassium carbonate (218.8 mg, 1 .58 mmol), ethyl 5-bromo-2-methyl- 1 , 3-thiazole-4-carboxylate (p68, 200 mg, 0.72 mmol) and Ethyl 6-(4-chlorophenyl)-3-oxo-2, 3-d ihyd ropyridazine-4-carboxylate (250 mg, 0.9 mmol) was dissolved in DMF (12 mL). (5-Chloropyridin-3-yl)boronic acid (282 mg, 1.79 mmol), 2, 2?- bipyridine (700.5 mg, 4.48 mmol), sodium carbonate (0.114 g, 1.076 mmol), and anhydrous copper diacetate (407 mg, 2.24 mmol) were added. The reaction mixture was stirred for 4 h at80C, cooled down followed by the addition of 2.7 mL of aqueous 2N sodium hydroxide solution. It was stirred overnight, water was added and the precipitate was filtered off and dried in vacuum to yield 402 mg of the title compound.LC-MS (Instrument: Waters Acquity UPLC-MS SQD 3001; column: Acquity UPLC BEH 0181.7 50x2.lmm; eluentA: water + 0.lvol% formic acid (99%), eluent B: acetonitrile; gradient: 0-1 .6 mm 1-99% B, 1.6-2.0 mm 99% B; flow 0.8 mL/min; temperature: 6000; injection: 2 pL; DAD scan: 210-400 nm; ELSD): R1 = 1.25 mm; MS (ESIpos): mlz = 364.0 [M+H]

Molecular Weight:157.36
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:157.0101863
Monoisotopic Mass:157.0101863
Topological Polar Surface Area:53.4
Heavy Atom Count:10
Complexity:114
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes