4-bromo-2-methyl-isoquinolin-1-one

4-[4-(3-Hydroxy-azetidin-1-ylmethyl)-3, 5-dimethoxy-phenyl]-2-methyl-2H-isoquinolin-1-one (II-1) 4-Bromo-2-methyl-2H-isoquinolin-1-one Q-1 (0.070 g; 0.294 mmol) and 1, 1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (0.025 g; 0.029 mmol) are added to a solution of 1-[2, 6-dimethoxy-4-(4, 4, 5, 5-tetramethyl[1, 3, 2]dioxaborolan-2-yl)-benzyl]-azetidin-3-ol K-3 followed by addition of a 2N sodium bicarbonate solution (0.368 mL; 0.735 mmol). The reaction mixture is stirred at 100° C. for 1 h. The reaction mixture is then cooled to RT, water is added and the mixture is filtered. The filtrate is purified by RP HPLC (column: X-Bridge C-18 30*50 mm). The product containing fractions are combined and concentrated under reduced pressure and further purified by NP silica gel chromatography Combiflash (column Redisep Rf, 12 g; gradient: DCM/MeOH/NH3=100percent/0percent to 10percent/0.1percent over 28 column volumes; flow rate=30 mL/min; detection wavelength: 254 nm). The product containing fractions are combined and concentrated under reduced pressure, dissolved in acetonitrile/water=1:1 and freeze dried. HPLC-MS: (M+H)+=381; tRet=1.02 min; method M14-(3-Amino-4-methyl-phenyl)-2-methyl-2H-isoquinolin-1-one (II-35') 4-Bromo-2-methyl-2H-isoquinolin-1-one Q-1 (0.186 g; 0.779 mmol), 3-amino-4-methylphenyl boronic acid K-20 (0.120 g; 0.779 mmol) and 1, 1'-bis(diphenylphosphino)ferrocene palladium(II) dichloride (0.064 g; 0.078 mmol) are dissolved in DMF (0.8 mL). A 2N sodium bicarbonate solution (0.974 mL; 1.947 mmol) is added and the reaction mixture is stirred under argon at 100° C. for 1 h. The reaction mixture is then cooled to RT, water is added and the mixture is filtered. The filtrate is purified by NP silica gel chromatography Combiflash (column Redisep Rf, 12 g; gradient: DCM/MeOH=100percent/0percent to 95percent/5percent over 26.5 column volumes; flow rate=30 mL/min; detection wavelength: 254 nm). The product containing fractions are combined and concentrated under reduced pressure, dissolved in acetonitrile/water=1:1 and freeze dried. HPLC-MS: (M+H)+=265; tRet=1.06 min; method M1

Molecular Weight:238.08
XLogP3:1.9
Hydrogen Bond Acceptor Count:1
Exact Mass:236.97893
Monoisotopic Mass:236.97893
Topological Polar Surface Area:20.3
Heavy Atom Count:13
Complexity:262
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes