5,6-DICHLOROBENZIMIDAZOLE

Purple Solid

General procedure: A 16 mL vial with a PTFE/silicone septum and a nitrogen-bubbler line was charged with N-benzylbenzimidazole (208.1 mg, 1.0 mmol), Pd/C (10 wt percent, dry powder, reduced) (20 mg) and THF (5 mL). The mixture was treated at rt with triethylsilane (320 µL, 2.0 mmol) and then stirred under nitrogen for 14 h at rt. The mixture was filtered through a 0.45 µM PTFE syringe filter and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (0 to 10percent MeOH/ dichloromethane) to afford benzimidazole as a colorless solid (117.6 mg, 0.996 mmol 99percent). The reactions generally exhibit an induction period of 5 to 30 min as indicated by the initiation of gas release (i.e., bubbling) from the reaction mixture. The use of Pd/C on a dry matrix is imperative as wet Pd/C results in decreased yield or no reaction.General procedure: A mixture of 1a (1b-1n, 0.4 mmol) and PhSiH3 (98 mL, 1.6 mmol)in N, N-dimethylformamide 2a (2b-2c, 1 mL) was stirred at 120 °C for 12 h. When the reaction was completed, the resulting mixture was extracted with ethyl acetate three times. The combined organic layer was washed by NaCl aqueous solution and dried over anhydrous Na2SO4, after which the solvent was removed under reduced pressure. The residue was purified by column chromatography onsilica gel with petroleum ether and ethyl acetate (6:1-1:2) to give the corresponding product 3a (3b-3p).Example 22[01611 Preparation of 5, 6-dichloro-1H-benzoimidazole. EMI53.1[0162] 4, 5-Dichlorobenzene-1, 2-diamine (500 mg, 2.82 mmol) was dissolved in 10 mL of HCOOH and stirred under reflux for 1 hour. The solvent was removed in vacuo, the residue was dissolved in EtOAc and NEt3 (3 drops) was added. The solvent was removed in vacuo and the crude product was purified by flash chromatography to give 5, 6-dichloro- IH-benzoimidazole. [0163] Yield:480 mg (91percent) ; Rf = 0. 5 (10percentMeOH-CH2Cl2). lH NMR (acetone-d6, 300 MHz)8 7.83 (2H, s), 8.29 (1H, s), 11.8 (1H, br).Step A-5, 6-Dicnloro-1H-benzimidazole To 4, 5-dichloro-1, 2-benzenediamine (15 g, 85 mmol) was added trimethylorthoforrnate (850 mL) and formic acid (0.32 mL) and the reaction mixture heated to 70° C. overnight. Silica was added and the volatiles evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 15percent MeOH:DCM) to give 12 g (76percent) of the title compound. Example 71 ; 3-(((1 ^-1'f2-Chloro-3-(4-^peridinylpxy)pheπytjepercentj}g^-5-(5

A benzimidazole derivative as potent inhibitor of milk xanthine oxidase

Molecular Weight:187.02
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:185.9751535
Monoisotopic Mass:185.9751535
Topological Polar Surface Area:28.7
Heavy Atom Count:11
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes