ChemicalBook CAS DataBase List Bifonazole

Bifonazole synthesis

8synthesis methods

Product Name:Bifonazole
CAS Number:60628-96-8
Molecular formula:C22H18N2
Molecular Weight:310.4

13.6 g (0.2 mol) of imidazole are dissolved in 150 ml of acetonitrile and 3.5 ml of thionyl chloride are added at 10°C. 13 g (0.05 mol) of (biphenyl-4-yl)- phenyl-carbinol are added to the solution of thionyl-bis-imidazole thus obtained. After standing for 15 hours at room temperature, the solvent is removed by distillation in vacuo. The residue is taken up in chloroform and the solution is washed with water. The organic phase is collected, dried over sodium sulfate and filtered and the solvent is distilled off in vacuo. The oily residue is dissolved in ethyl acetate and freed from insoluble, resinous constituents by filtration. The solvent is again distilled off in vacuo and the residue is purified by recrystallization from acetonitrile, 8.7 g (56% of theory) of (biphenyl-4-yl)-imidazol-1-yl-phenylmethane [alternatively named as Bifonazole
of melting point 142°C are obtained.

288-32-4 Synthesis

288-32-4
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613-42-3 Synthesis

613-42-3
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$8.00/1g

60628-96-8
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$5.00/250mg

Yield:60628-96-8 77%

Reaction Conditions:

Stage #1:4-benzylbiphenyl with N-Bromosuccinimide;2,2'-azobis(isobutyronitrile) in tetrachloromethane for 0.833333 h;Inert atmosphere;Reflux;
Stage #2:1H-imidazole with potassium carbonate in acetonitrile for 1 h;Reflux;

Steps:

89 Example 89
Under a nitrogen atmosphere, a mono-substituted aromatic substrate 8e (6.0 mmol), thioanthracene-S-oxide (7.2 mmol), DCM (30.0 mL) were added to a 25 mL Schlenk tube, followed by stirring at -40°C.After slowly dropping Tf2O (7.2 mmol), it was stirred at -40°C for 30 minutes, followed by stirring at room temperature for 1 hour.Then, under a nitrogen atmosphere, sodium bicarbonate (0.6 mmol), pinacol phenyl borate (9.0 mmol), bis(tri-tert-butylphosphine) palladium (0.3 mmol), DMF (30.0 mL) was added, and the bottle was screwed tightly. Cover and react at 50°C for 12 hours.After the reaction was completed, the celite was filtered, and the solvent was removed under reduced pressure. The crude product was separated and purified by a preparation plate (toluene/hexane (40/1)) to obtain a white solid 11 (1.24 g) with a yield of 84%.Under a nitrogen atmosphere, 11 (0.2 mmol), NBS (0.2 mmol), AIBN (0.02 mmol), and CCl4 (2.5 mL) were added to a 20 mL reaction flask.Reflux for 50 minutes.Cooled to room temperature, the reaction mixture was filtered and washed twice with n-hexane (2×2 mL).After concentration, imidazole (1.57 mmol), potassium carbonate (0.61 mmol) and acetonitrile (4.3 mL) were added.Reflux for 1 hour.After cooling to room temperature, the reaction was quenched by adding a small amount of DCM, filtered through celite, and the solvent was removed under reduced pressure. The crude product was separated and purified by the preparation plate (hexane/EtOAc (5/3)) to obtain the drug molecule 12 (Bifonazole) (47.9mg ), yield 77%.

References:

Chinese Academy Of Sciences Shanghai Organic Chemistry Institute;Wang Peng;Chen Xiaoyue;Nie Xiaoxue;Wu Yichen CN111187130, 2020, A Location in patent:Paragraph 0506-0508; 0510

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288-32-4 Synthesis

288-32-4
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$5.00/25g