Boronic acid, (4-hydroxy-3-methylphenyl)- (9CI)

A mixture of tert-butyl (3S)-3-[(2-bromothiazol-4-yl)carbamoylamino]piperidine-1- carboxylate (prepared as described for Example 15, step a; 0.28 g, 0.69 mmol), 4-hydroxy- 3-methylbenzeneboronic acid (0.12 g, 0.76 mmol), Pd(PPh3)4 (0.04 g, 0.035 mmol) and K2CO3 (0.29 g, 2.07 mmol) in 1 , 4-dioxane (3 ml_) and water (1 ml_) was heated at 90C in the microwave for 30 min. The reaction mixture was diluted with EtOAc (50ml_), washed with water (2x 50 ml_) and evaporated. The crude product was purified using column (0640) chromatography, eluting with a gradient of 0-100% EtOAc / cyclohexane. Fractions were combined and evaporated to give tert-butyl (3S)-3-[[2-(4-hydroxy-3-methyl-phenyl)thiazol-4- yl]-carbamoylamino]piperidine-1-carboxylate, (0.165 g, 55%) as a yellow solid (0641) m/z ES+ [M+H]+ 496; 1 H NMR (400 MHz, DMSO-d6) d 9.92 (s, 1 H), 9.24 (s, 1 H), 7.58 (d, J = 2.1 Hz, 1 H), 7.54 - 7.50 (m, 1 H), 6.99 (s, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 6.54 (s, 1 H), 3.62 - 3.53 (m, 1 H), 3.45 - 3.35 (m, 1 H), 2.58 - 2.51 (m, 1 H), 2.17 (s, 3H), 1.84 - 1.76 (m, 1 H), (0642) 1.67 - 1.56 (m, 1 H), 1.50 - 1.28 (m, 11 H).Compound 239 was prepared starting from compound XXg in a palladium mediated reaction using (4-hydroxy- 3- methylphenyl)boronic acid instead of compound VI as indicated in scheme 2. Compound XXg (2.13 g; 7.15 mmo 1 eq), sodium carbonate (16.5 g; 15.57 mmol; 2.2 eq) and (4-hydroxy-3- methylphenyl)boronic acid (1.30 g; 8.58 mmol; 1.2 eq) were suspended in DMF (50 mL) to give a black suspension. The solution was stirred under Argon for 30 mm. Tetrakis(triphenylphosphine)palladium(0) (248 mg; 0.2 15 mmol; 0.03 eq) was added and the reaction mixture was heated with a pre-heated oil-bath to 125C.The reaction mixture was stirred for 2.5 h at 125C and evaporated. The residue was diluted in 125 ml water and neutralized to pH 5-6 with 15 ml 2N HC1 and extracted with DCM. The organic layer was washed with a NaC1 solution, dried over MgSO4, and evaporated. The residue was purified by flash chromatography(40g silica gel, 30% EtOAc/n-heptane) giving ethyl 4-(2-(4-hydroxy-3- methyiphenyl) -7, 8- thhydropyrido [4, 3 -d]pyrimidin-6(5H) -yl) -3- methylbutanoate with a yield of 1.59 g (4.30 mmol; 60.1%).

suzuki reaction

Molecular Weight:151.96
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:152.0644743
Monoisotopic Mass:152.0644743
Topological Polar Surface Area:60.7
Heavy Atom Count:11
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes