Piperidin-4-yl-zetidine diamides as monoacylglycerol lipase inhibitors
A pyridyl and phenyl technology, applied in the directions of anti-inflammatory agents, non-central analgesics, medical preparations containing active ingredients, etc., can solve problems such as difficulty in separating side effects
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
example 1
[0324]
[0325] A. tert-Butyl 3-(pyridin-4-yl)azetidine-1-carboxylate, 1c. equipped with thermocouple, magnetic stirrer, condenser, heating mantle and N 2A 1-liter 3-neck round bottom flask with an inlet adapter was charged with anhydrous dimethylacetamide (DMA, 100 mL) and zinc (42.94 g, 650.2 mmol). The mixture was stirred at 20 °C while 1,2-dibromoethane (DBE, 5.38 mL, 62.34 mmol) and trimethylchlorosilane (TMS-Cl, 7.54 mL, 59.28 mmol). The resulting slurry was aged for 15 min. A solution of tert-butyl 3-iodoazetidine-1-carboxylate 1a (122.78 g, 420.69 mmol) in DMA (201 mL) was added dropwise at a rate to keep the temperature below 65 °C over 1 h, and the milky The suspension was stirred for 30 min while cooling slowly to 20 °C.
[0326] in N 2 Under the conditions equipped with thermocouple, mechanical stirrer, condenser, heating mantle and N 2 [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (4.73 g, 5.74 mmol), cuprous iodide ...
example 2
[0337]
[0338] A. 3-Chloro-6-fluorobenzo[b]thiophene-2-carbonyl chloride, 2b. Thionyl chloride (73.7 mmol, 5.36 mL) was added to a mixture of 4-fluorocinnamic acid 2a (21.1 mmol, 3.5 g) and pyridine (2.53 mmol, 0.2 mL). The mixture was heated at 135 °C for 30 min, then cooled to room temperature. The crude mixture was triturated with hot hexanes to remove the solid pyridine hydrochloride by-product. Compound 2b was isolated from the combined hexane solutions.
[0339]B. 4-{1-[(3-chloro-6-fluoro-1-benzothiophen-2-yl)carbonyl]azetidin-3-yl}-1-(1,3-thiazole-2 -ylcarbonyl)piperidine, Cpd8. Compound 2b (0.45mmol, 112mg) was dissolved in 4mL CH at 0°C 2 Cl 2 The solution in was added compound 1j mono-TFA salt (0.41mmol, 150mg) in Et 3 N (2.46mmol, 0.34mL) in solution. The resulting reaction mixture was stirred at 0 °C for 3 h. The crude product was purified by preparative reverse phase chromatography to provide 18 mg (9% yield) of Cpd8. 1 H NMR (CD 3 OD, 400MHz): δ=7.8...
example 3
[0343]
[0344] A. 3-Methyl-6-(trifluoromethyl)benzo[b]thiophene-2-carboxylate, 3c. Methyl thioglycolate 3b (30.3 mmol, 2.76 mL) was added dropwise to a suspension of NaH (60% oil dispersion, 75.8 mmol, 3.03 g) in 10 mL THF and 50 mL DMSO at 20 °C. The mixture was stirred for 15 min, and a solution of 1-(2-fluoro-4-(trifluoromethyl)phenyl)ethanone 3a (24.3 mmol, 5.0 g) in 10 mL DMSO was added. The reaction mixture was stirred at 20 °C for 4 h, and water was added. The mixture was extracted with EtOAc. MgSO for organic layer 4 Drying and concentration afforded compound 3c as a white solid.
[0345] B.4-(1-{[3-methyl-6-(trifluoromethyl)-1-benzothiophen-2-yl]carbonyl}azetidin-3-yl)-1-(1 , 3-thiazol-2-ylcarbonyl)piperidine, Cpd20. To compound 1j mono-TFA salt (0.27mmol, 100mg) and compound 3c (0.30mmol, 78mg) in 4mL CH 2 Cl 2 Et was added to the stirred solution in 3 N (1.09 mmol, 0.15 mL). After 20 min at 20 °C, HATU (0.33 mmol, 125 mg) was added and the mixture was s...
PUM
Login to view more Abstract
Description
Claims
Application Information
Login to view more - 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.
© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap