Fused imidazole derivative having IDO/TDO inhibition activity and having structure represented by formula (I), preparation method and applications thereof
A compound and unsubstituted technology, applied in the field of fused imidazole derivatives and their preparation, can solve the problem of no IDO/TDO inhibitor on the market, etc.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0101] 1-((5H-imidazo[5,1-a]isoindol-5-yl)methyl)-3-(4-cyanophenyl)urea
[0102]
[0103] The first step: the preparation of 1-(2-bromobenzyl)-1H-imidazole
[0104]
[0105] Dissolve o-bromotoluene (20g, 117mmol), bromosuccinimide (22.0g, 123mmol), and azobisisobutyronitrile (1g) in dry carbon tetrachloride (200mL), and heat to reflux under nitrogen protection 16 hours. After the reaction was cooled to room temperature, it was filtered, imidazole (15.9 g, 234 mmol) and potassium carbonate (33 g, 234 mmol) were added to the filtrate, and heated to reflux for 5 hours under nitrogen protection. LC-MS showed that the reaction was complete, the reaction solution was filtered, the filtrate was concentrated, and the residue was dissolved in dichloromethane (100 mL) and washed with water (2×50 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered, concentrated, and the residue was purified by flash silica gel column to obtain 1-(2-bromobenzyl)...
Embodiment 2
[0129] 1-(4-cyanophenyl)-3-((6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)methyl)urea
[0130]
[0131] The first step: the preparation of 1-(2-fluoro-6-bromobenzyl)-1H-imidazole
[0132]
[0133] Dissolve 1-bromo-3-fluoro-2-toluene (8.0g, 42.3mmol), bromosuccinimide (9.0g, 50.8mmol), azobisisobutyronitrile (300mg) in dry tetrachloride carbon (100 mL), heated to reflux for 16 hours under nitrogen protection. After the reaction was cooled to room temperature, it was filtered, imidazole (8.7g, 126.9mmol) and potassium carbonate (17.5g, 126.9mmol) were added to the filtrate, and heated to reflux for 5 hours under nitrogen protection. LC-MS showed that the reaction was complete, the reaction solution was filtered, the filtrate was concentrated, and the residue was purified by flash silica gel column chromatography to obtain 1-(2-bromo-6-fluorobenzyl)-1H-imidazole (6.0 g).
[0134] The second step: the preparation of 6-fluoro-5H-imidazo[5,1-a]isoindole
[0135]
[0136...
Embodiment 3
[0151] 1-(4-bromophenyl)-3-((6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl)methyl)urea
[0152]
[0153] 2-(6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)acetic acid (200mg, 0.86mmol), diphenylphosphoryl azide (DPPA) (475mg, 1.72mmol), Triethylamine (180mg, 1.72mmol), p-bromoaniline (300mg, 1.72mmol) were dissolved in anhydrous toluene (20mL), and heated to reflux for 4 hours under nitrogen protection. LC-MS showed that the reaction was complete. The reaction solution was concentrated, and the residue was dissolved in dichloromethane (20 mL), washed with water (2×10 mL) and saturated brine (10 mL) successively. The organic phase was dried filtered and concentrated. The residue was purified by flash silica gel column and reverse flash column to give 1-(4-bromophenyl)-3-((6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl ) methyl) urea (6.0 mg).
[0154] LC-MS: 401.0,t R =2.118min;
[0155] 1 H NMR (400MHz,MeOD)δ7.96(s,1H),7.56-7.43(m,2H),7.42-7.31(m,2H),7.27-7.18(m,3H),7.15-7.03(m,1H ),5...
PUM
Abstract
Description
Claims
Application Information
- R&D Engineer
- R&D Manager
- IP Professional
- Industry Leading Data Capabilities
- Powerful AI technology
- Patent DNA Extraction
Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.
© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com