5-broMo-1,4-diMethyl-1H-iMidazole

PREPARATION 705-Bromo-1 , 4-dimethyl-1 H-imidazole To a cooled (0 °C) suspension of sodium hydride (60percent wt / wt in mineral oil, 149 mg, 3.73 mmol, 1.2 eq.) in anhydrous tetrahydrofuran (10 ml_), under an atmosphere of nitrogen, was added a solution of 5-bromo-4-methyl-1 H-imidazole (500 mg, 3.11 mmol) in tetrahydrofuran (5 ml_). The resulting mixture was stirred at room temperature for 30 min before adding methyl iodide (661 mg, 4.66 mmol, 1.5 eq.). The reaction mixture was stirred for 30 min before partitioning between ethyl acetate (100 ml_) and water (20 ml_). The organic phase was dried over magnesium sulphate and the resulting mixture filtered. The filtrate was evaporated under reduced pressure and the resulting residue purified by chromatography on silica gel (40 g) eluting with a gradient of methanol in dichloromethane (0:100 to 5:95) to give the title compound as a clear oil (80 mg, 15percent). (S)-6-(5 -bromo- 1 -(trans-4-hydroxycyclohexyl)- 1 H-benzo[d]imidazol-2-yl)- 1 -(3, 4- difluorophenyl)piperidin-2-one (intermediate 17, 100 mg, 0.20 mmol), bis(pinacolato)diboron (55 mg, 0.22 mmol), potassium acetate (30 mg, 0.31 mmol) and PdCl2(dppf) (15 mg, 0.02 1 mmol) were placed in a tube fitted with septum then evacuated and backfilled with nitrogen three times. 1, 4-dioxane (3 mL) was added and the mixture was evacuated and backfilled with nitrogen a further three times. The mixture was heated to 80 C for 1 h then cooled. A mixture of water (0.308 mL, 17.12 mmol) and (S)-5-(1-(4, 4-difluorocyclohexyl)-5- (4, 4, 5, 5-tetramethyl- 1, 3 , 2-dioxaborolan-2-yl)- 1H-benzo[d]imidazol-2-yl)- 1 -(3, 4- difluorophenyl) pyrrolidin-2-one (0.373 g, 0.308 mmol) and Example 4545-{7-Methanesulfonyl-5- [(S)-oxan-4-yl(phenyl)methylj -5H-pyrido [3, 2-bj indol-3-yl}-1 , 4-dimethyl-1 H-imidazole (S)-(7-(Methylsulfonyl)-5 -(phenyl(tetrahydro-2H-pyran-4-yl)methyl)-5H- pyrido [3 , 2-b]indol-3 -yl)boronic acid (30.0 mg, 0.0650 mmol) and 5 -bromo- 1 , 4-dimethyl- 1H-imidazole (11.3 mg, 0.0650 mmol) were dissolved in 1.5 mL of dioxane and 0.5 mLof water. To this was added potassium carbonate (26.8 mg, 0.194 mmol) andPdC12(dppf)-CH2C12 adduct (3.69 mg, 4.52 jimol), and the reaction mixture was degassedby bubbling in argon while sonicating for 5 mm. The vial was capped and heated at 100C for 1 h. The crude material was purified via preparative LC/MS (Preparative HPLCMethod 1) with the following modifications: Gradient 3 0-70% B over 20 mm. Fractionscontaining the desired product were combined and dried via centrifugal evaporation. Theyield of the product was 5.80 mg, and its estimated purity by LCMS analysis was 91%.Two analytical LC/MS injections were used to determine the final purity. Injection 1:LC/MS Method 3, HPLC RT = 1.32 mm. Injection 2: LC/MS Method 4, HPLC RT =2.32 mm. 'H NMR (500MHz, DMSO-d6) oe 8.58 (s, 1H), 8.45 (d, J8.1 Hz, 1H), 7.85 (d, J=8.4 Hz, 1H), 7.74 (s, 1H), 7.68 (d, J=7.7 Hz, 2H), 7.34 (t, J=7.5 Hz, 2H), 7.30-7.23 (m, 1H), 6.01 (d, J=11.0 Hz, 1H), 3.91-3.84 (m, 1H), 3.73 (d, J=8.1 Hz, 1H), 3.54-3.45 (m, 1H), 3.26 (t, J=11.7 Hz, 1H), 2.17 (s, 3H), 1.91 (s, 6H), 1.73 (br. s., 1H), 1.63 (d, J=8.8Hz, 1H), 1.46-1.28 (m, 1H), 0.94 (d, J=11.7 Hz, 1H).(S)-(7-(Methylsulfonyl)-5-(phenyl(tetrahydro-2H-pyran-4-yl)methyl)-5H-pyrido[3, 2-b]indol-3-yl)boronic acid (30.0 mg, 0.0650 mmol) and

Molecular Weight:175.03
XLogP3:1.4
Hydrogen Bond Acceptor Count:1
Exact Mass:173.97926
Monoisotopic Mass:173.97926
Topological Polar Surface Area:17.8
Heavy Atom Count:8
Complexity:86.5
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes