Boronic acid, [4-(difluoromethoxy)phenyl]- (9CI)

A mixture of 8-bromo-2-(2, 2-difluoroethoxy)-6-(2-methyl-2H- indazol-5-yl)pyrido[3, 4-b]pyrazin-7(6H)-one (20 mg, 0.046 mmol, 1.0 eq.), (4- (difluoromethoxy)phenyl)boronic acid (17 mg, 0.092 mmol, 2.0 eq.), Pd(dppf)Ch (6.8 mg, 0.009 mmol, 0.2 eq.) and CS2CO3 (50 mg, 0.138 mmol, 3.0 eq.) in a dioxane/H20 mixture (0.5 mL, 9/1, v/v) was stirred at 100 C under N2 atmosphere for 15 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by RP-prep-HPLC to afford 2-(2, 2- difluoroethoxy)-8-(4-(difluoromethoxy)phenyl)-6-(2-methyl-2H-indazol-5- yl)pyrido[3, 4-b]pyrazin-7(6H)-one (139-A). [00963] NMR (400 MHz, DMSO-de) d: 8.85 (s, 1H), 8.51 (s, 1H), 8.26 (s, 1H), 7.93 (d, J = 1.2 Hz, 1H), 7.73-7.67 (m, 3H), 7.35 (dd, J = 9.2 Hz, 2.0 Hz, 1H), 7.29 (t, JHF = 74.2 Hz, 1H), 7.18 (d, J = 8.8 Hz, 2H), 6.41 (tt, JHF = 54.2 Hz, J = 3.2 Hz, 1H), 4.57 (td, JHF = 14.8 Hz, J = 3.2 Hz, 2H), 4.23 (s, 3H). LC-MS (ESI): m/z 500 [M+H]+.To a solution of compound -(4-bromo-2, 6-difluorophenyl)spiro[cyclopropane-l, 3'- imidazo[l, 2-a]imidazol]-2'(l'H)-one (Example A.4) (150 mg, 0.440 mmol, 1 eq.) and 4- (difluoromethoxy)phenylboronic acid (165 mg, 0.880 mmol, 2 eq.) in DMF (10 ml) and H20 (0.1 ml) was added Na2C03 (93.5 mg, 0.880 mmol, 2 eq.) at 25C and the reaction mixture purged with argon for 10 min. Then Pd(PPh3)4 (51 mg, 0.040 mmol, 0.1 eq.) was added and the reaction mixture again purged with argon for 10 min. The reaction mixture was stirred at 80C for 2 h. The reaction was was diluted with EtOAc (100 ml) and the organic layer was washed with water (2 x 20 ml) water and brine (20 ml), dried over Na2S04 and concentrated in vacuo. The crude product was then purified by flash chromatography (5% EtOAc in hexane) to give 7'- [4-[4-(difluoromethoxy)phenyl]-2, 6-difluoro-phenyl]spiro[cyclopropane-l, 5'-imidazo[l, 2- a]imidazole]-6'-one (200 mg, 0.500 mmol, 86.58% yield) as a yellow solid. M+H+ = 404.0Step 3: 4-Bromo-1-(4-(difluoromethoxy)phenyl)-8, 9-dihydro-7H-6-oxa-2, 9a-diazabenzo[cd]azulene A mixture of 4-bromo-1-iodo-8, 9-dihydro-7H-6-oxa-2, 9a-diazabenzo[cd]azulene (500 mg, 1.3 mmol), General procedure: To a solution of 3-bromo-6-[4-(propan-2-yloxy)phenyl]imidazo[1 , 2-a]pyridine (20 mg, 0.06 mmol) in 2 mL THF:Water 3:1 was added 4-cyclopropylboronic acid (12 mg, 0.072 mmol), potassium carbonate (5 mg, 0.18 mmol), and Pd(dppt)C12 dichloromethane complex (5mg, .006 mmol). The mixture was capped tightly and degassed by bubbling nitrogen through the septum for 5 minutes. The resultingsolution was heated to 100C for 15 minutes in a microwave reactor and allowed to cool. The mixture was then diluted with ethyl acetate, washed with water (2x) and brine (lx), dried over sodium sulfate, and evaporated. The crude oil was purified by flash chromatography on silica (3:7hexanes:ethyl acetate, isocratic) to provide 13 mg of the title compound as a light yellow oil.Step J: To dichloromethane (2.0 mL) was added 4-(4-(7-oxo-3-(trifluoromethyl)-4, 5-dihydro-1H-pyrazolo[3, 4-c]pyridin-6(7H)-yl)piperidin-1-yl)morpholin-3-one (60 mg, 0.2 mmol),

Molecular Weight:187.94
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:3
Exact Mass:188.0456306
Monoisotopic Mass:188.0456306
Topological Polar Surface Area:49.7
Heavy Atom Count:13
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes