4-Bromo-1-ethyl-1H-pyrazole

a) 4-Bromo- 1 -ethyl- 1 H-pyrazoleTo a solution of 4-bromo-l H-pyrazole (5 g, 34 mmol) in DMF were added Ka4-Bromo-1-ethyl-1H-pyrazole_: To a suspension of NaH (0.196 g, 8.16 mmol) in THF (15 ml_) was added 4-bromo- 1 H-pyrazole (1 g, 6.80 mmol) in THF (5 ml_) at 0 °C, under nitrogen atmosphere, and strirred for 20 min. Ethyl iodide (0.825 ml_, 10.21 mmol) was added at 0 °C and stirred at RT for 2 h. The reaction mixture was quenched with cold water, and extracted with EtOAc (2X). The organic layer washed with brine, dried under anhydrous NaStep 3: Synthesis of 4-bromo-1-ethyl-1H-pyrazole (4):j00341j To a stirred solution of NaH (34.0 g, 0.85 mol; 60percent in mineral oil) in THF (400 mL) was added a solution of 4-bromo-1H-pyrazole (50 g, 0.34 mol) in THF (100 mL) at 0 °C under inert atmosphere. The reaction mixture was warmed to RT and maintained at same temperature for 1 h. The reaction mixture was cooled again to 0 °C and added EtI (63.67 g, 0.408 mol) slowly for 5 mm. The resultant solution was allowed to warm to RT and then stirred for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with ice-cold water (100 mL) and extracted with EtOAc (3 x 250 mL). The combined organic extracts were dried over Na2504, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel chromatography; 4-6percent EtOAc/Hexanes) to afford compound 4 (43 g, 72percent) as a pale yellow liquid. 1H NMR (500 MHz, CDC13): ö 7.45 (s, 1H), 7.41 (s, 1H), 4.15 (q, J = 7.5 Hz, 2H), 1.47 (t, J = 7.5 Hz, 3H); MS (ES): mlz 175.0 (M + Hj.Step 3: To a stirred solution of NaH (34.0 g, 0.85 mol; 60percent in mineral oil) in THF (400 mL) was added a solution of 4-bromo-1H-pyrazole (50 g, 0.34 mol) in THF (100 mL) at 0 °C under inert atmosphere. The reaction mixture was warmed to RT and maintained at same temperature for 1 h. The reaction mixture was cooled again to 0 °C and added EtI (63.67 g, 0.408 mol) slowly for 5 mm. The resultant solution was allowed to warm to RT and then stirred for 16 h. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with ice-cold water (100 mL) and extracted with EtOAc (3 x 250 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel chromatography; 4-6percent EtOAc/Hexanes) to afford compound 4 (43 g, 72percent) as a pale yellow liquid. 1H NMR (500 MHz, CDC13): ö 7.45 (s, 1H), 7.41 (s, 1H), 4.15 (q, J = 7.5 Hz, 2H), 1.47 (t, J = 7.5 Hz, 3H); MS (ES): m/z 175.0 (M + H).In a RBF previously equipped with a magnetic stirrer and nitrogen balloon was taken 4- bromo-1 -ethyl-1 H-pyrazole (2.15 g, 12.33 mmol) in THF (15 ml) and the mixture was cooled at -78 C. n-BuLi (2.5 M in THF, 22.4 ml, 13.56 mmol) was added drop-wise to the reaction mixture and it was stirred at same temperature for 2 h. 5-nitro-2- phenoxybenzaldehyde (commercially available, 3.0 g 12.33 mmol) was dissolved in THF (5 ml) and the solution was added drop-wise in to reaction mixture at -78 C. The reaction mixture was stirred at -78 C for 2 h and then allowed to reach room temperature and stirred for 12 h. The reaction mixture was quenched with ammonium chloride solution (50 ml) and extracted with EtOAc (2 x 100 ml). The combined organic layer was washed with brine (100 ml) and dried over sodium sulphate and the solvent removed under reduced pressure to obtain 2 g of the crude title compound that that was used in the next step without further purification. MS (ES+) m/z 340 [M+H]+In a nitrogen atmosphere, a mixture of 1.62 g of 4-methoxy-3-methyl-phenylboronic acid, 1.57 g of [0511j A solution of (6-bromo- i-ethyl-S -fluoro- 1 H-benzo [d]imidazol-2- yl)diphenylmethanol (0.21 g, 0.50 mmol), 4, 4, 4?, 4?, S , S , S?, S?-octamethyl-2, 2?-bi( 1, 3, 2- dioxaborolane) (0.25 g, 1.0 mmol), i, i?-bis(diphenylphosphino)ferrocenepalladium(II) dichloride (0.035 g, 0.050 mmol) and potassium acetate (0.098 g, 1.0 mmol) in dioxane (10 mL) was stirred at reflux for 5 hours. After cooling to ambient temperature, 4-bromo-i-ethyl- 1H-pyrazole (0.088 g, 0.5 mmol), tetrakis(triphenylphosphine)palladium (0) (0.055 g, 0.05 mmol), cesium carbonate (0.33 g, 1.0 mmol) and water (3 mL) were added. The reaction mixture was stirred at 100 C for 12 hours. After cooling to ambient temperature, ethyl acetate and water were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to give (i-ethyl-6-(i-ethyl-1H-pyrazol-4-yl)-5-fluoro- 1H-benzo[d]imidazol-2-yl)diphenylmethanol (0.10 g, 45%) as solid. LCMS ESI (+) mlz 441 (M+H).

Molecular Weight:175.03
XLogP3:1.2
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:173.97926
Monoisotopic Mass:173.97926
Topological Polar Surface Area:17.8
Heavy Atom Count:8
Complexity:76.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes