Parallel solution-phase synthesis of substituted 2-(1,2,4-triazol-3-yl)benzimidazoles

Tetrahedron Letters

Volumn 47, Issue 46, 2006, Pages 8025-8027

  Ivanova, Natalya V ^a   Sviridov, Sergey I ^b   Stepanov, Aleksandr E ^a  

^a MIREA RUSSIAN TECHNOLOGICAL UNIVERSITY   (Russian Federation)

^b ChemBridge Corporation   (Russian Federation)

Author keywords

1,2,4 Triazoles; Benzimidazoles; Solution phase parallel synthesis

Indexed keywords

1,2 PHENYLENEDIAMINE; 2 (1,2,4 TRIAZOL 3 YL)BENZIMIDAZOLE; ALDEHYDE; BENZIMIDAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; PURIFICATION;

EID: 33749538391     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2006.09.061     Document Type: Article

References (29)

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24. A 48-well array of 6 mL glass vials was charged with 400 μL of solutions of the corresponding aldehydes (0.2 mmol) and 400 μL of 1,2-phenylenediamines (0.2 mmol) in ethanol. The rack of tubes was covered with a Teflon/Silicone cap mat-lined plate. The reaction mixtures were vigorously stirred at 85 °C for 12 h. Then the cover was opened, and the solvent was evaporated under stirring at 85 °C. Ethanol (500 μL) was added, and the mixtures were evaporated again in the air under stirring and heating. This procedure was repeated 2-3 times. The oxidation process was monitored by HPLC. Crude products were purified by mass-guided preparative HPLC.
25. 2S was evolved). The reaction mixtures were kept at 130 °C for 5 h, then cooled, and filtered to remove sulfur and washed with DMF (3 × 400 μL). The solvent was evaporated to dryness in a Savant evaporator at 60 °C for 6 h. Crude products were purified by mass-guided preparative HPLC.
26. A 4 M solution of HCl in dioxane (1 mL) was added to each vial. The reaction mixtures were stirred for 3 h. The solvent was evaporated to dryness in a Savant evaporator at 60 °C for 6 h.
27. The products were dissolved in dichloromethane (500 μL). The solutions were cooled to 0 °C in an ice bath. A mixture of TFA (1 mL), anisole (0.2 mL), and dichloromethane (2 mL) for each reaction was prepared. This mixture was added dropwise to the solutions of the products under cooling and stirring. The cooling bath was removed, and stirring was continued for 3 h. The solvent was evaporated to dryness in the air.
28. For sample purification, a 1100 LCMSD purification platform (Agilent Technologies, USA) consisting of two preparative pumps, an autosampler, a variable wavelength detector, a fraction collector, and a mass-spectrometric detector was used. A Kromasil 7 μm C18 150 × 30 mm column (Akzo Nobel, Sweden) was employed. Gradient separation was used from 10% acetonitrile, 90% water, 0.1% TFA to 0.1% TFA in acetonitrile. For quality control a 1100 LCMSD (Agilent Technologies, USA) was used. A Hi-Q 5 μm C18 50 × 4.6 mm column (Peeke Scientific, USA) was used. The gradient separation was from 2.5% acetonitrile, 97.5% water, 0.1% TFA to 0.1% TFA in acetonitrile.
29. 3COOH (398.65): C, 53.93; H, 3.78; N, 21.08. Found: C, 54.28; H, 3.84; N, 21.19.