3-Bromo-2,4-dimethylpyridine

Bromination of 2, 4-lutidineTo 2, 4-lutidine (5.39 mL, 46.7 mmol, 1 eq.) was added oleum (50 mL, containing 20percent free SOCrude 4-(2-cyclopropyl-7-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-5-yl)-3, 5-dimethylisoxazole (280 mg crude mixture, 0.2 mmol) from the previous step was added to a 0.5 to 2 mL Smith process vial equipped with a stir bar. To the reaction vessel was added Example 22, 4-Dimethyl-3-(4, 4, 5, 5-tetramethyl-l, 3, 2-dioxaborolan-2-yl)pyridine.To a solution of 3-bronio-2, 4-diniethylpyridine (476 nig, 2.56 mmol) in DMSO (14 mL) was added bis(pinocolato) diboron (3.25 g, 12.8 mmol), potassium acetate (1.26 g, 12.8 mmol) andPdCl2(dppf)-CH2Cl2 adduct (209 mg, 0.256 mmol). Reaction was heated at 95°C for 16 h. Water was added and the aqueous phase was extracted with EtOAc (3x). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduce pressure. The residue was purified via FCC (40-70percent EtOAc/heptane) to give the title compound. lH NMR (400 MHz, CDC13) delta ppm 8.35 (d, J=5.1 Hz, 1 H), 6.91 (d, J=5.1 Hz, 1 H), 2.64 (s, 3 H), 2.42 (s, 3 H); 1.43 (s, 12 H); MS (ESI+) m/z 234 A (M+H)+.A mixture of Dimethyl 3-bromopyridine-2, 4-dicarboxylate 113-Bromo-2, 4-lutidine 10 (7.00 g, 38 mmol, 1 eq.) and water (100 mL) were heated to 100 0C, and a solution of NaOH (1.05 g, 26 mmol, 0.7 eq.) in water (15O mL) was added. KMnO4 (29.7 g, 188 mmol, 5 eq.) was then added in portions over 30 min under vigorous stirring. The resulting dark suspension was stirred under reflux until the colour of KMnO4 had vanished completely (2-3 h, determined in 3 independent experiments). The hot solution was filtered and solids washed with hot water (3 * 50 mL). The filtrate was concentrated to ca. 50 mL in vacuo and neutralised with cone. H2SO4. The solution was concentrated in vacuo, the residue was coevaporated with toluene and suspended in MeOH (200 mL). Cone. H2SO4 (10 mL) was added, the resulting suspension was refluxed overnight and then cooled to room temperature and concentrated in vacuo. The residue was taken up in water, the pH was adjusted to pH 9 by careful addition Of Na2CO3 and the basic solution was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The residue was purified by automated column chromatography (Biotage KP-SIL.(TM). SNAP 100 g cartridge) to afford 11 (4.62 g, 45percent) as a white solid.1H NMR deltaH (400 MHz; CDCl3) 3.98 (s, 3H, OCH3), 4.01 (s, 3Eta, OCH3), 7.60 (d, J=5.0 Hz, IH, pytfortho), 8.64 (d, J=5.0 Hz, IH, pyHmeta); 13C NMR deltac (100 MHz; CDCl3) 53.2 (CH3), 53.3 (CH3), 115.6 (ArC), 125.2 (ArCH), 142.1 (ArC), 148.0 (ArCH), 152.4 (ArC), 164.9 (CO), 165.4 (CO); IR vmax (KBr diskycm'1 3019, 2958, 1743, 1449, 1421, 1279, 1202, 1171; HRMS (ESI+) for C9H8BrNNaO4 requires 295.9529, found (M+Na+) 295.9524; Microanalysis for C9H8BrNO4 requires C 39.44, H 2.94, N 5.11; found C 39.54, H 2.95, N 5.02;

Molecular Weight:186.05
XLogP3:2.3
Hydrogen Bond Acceptor Count:1
Exact Mass:184.98401
Monoisotopic Mass:184.98401
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:94.9
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes