Benzopyridine azepines and their application as antitumor drugs
A technology of benzopyridine azepine and benzopyridine, which is applied in the direction of antineoplastic drugs, drug combinations, medical preparations containing active ingredients, etc.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0119] Synthesis of 1-[(4-fluorophenyl)amido]cyclopropanecarboxylic acid (Intermediate 2)
[0120] 1.3-Cyclopropanedicarboxylic acid (13.01g, 0.10mol) was dissolved in THF 120mL, under nitrogen protection, triethylamine (10.12g, 0.10mol) was slowly added dropwise at 0°C, and stirred for 15min. Slowly add SOCl2 (9.95 g, 0.10 mol) dropwise to the above system, maintain this temperature, and continue stirring for 30 min. Finally, 60 mL of a THF solution dissolved in 4-fluoroaniline (12.22 g, 0.11 mol) was added dropwise to the reaction liquid, and the reaction was completed under ice bath conditions. After the reaction, the reaction solution was adjusted to pH 9.0 with 10% sodium hydroxide solution, and after stirring for 10 min, the pH of the system was adjusted to 5.0 with 1N HCl, and a solid precipitated out, which was filtered after stirring for 15 min. The filter cake was washed with water until neutral, and dried in vacuum to obtain 14.71 g of a white solid with a yield of...
Embodiment 2
[0124] Synthesis of N-(4-fluorophenyl)-N-(4-hydroxyphenyl)cyclopropane-1,1-diamide (intermediate 3-1)
[0125]4-aminophenol (0.59g, 5.38mmol) and intermediate 2 (1g, 4.48mmol) were dissolved in DMF 15mL, EDC.HCl (1.03g, 5.38mmol) was added thereto, and the reaction was stirred at room temperature for 3h. After the reaction, add water to the reaction solution to precipitate a white solid, add 1N HCl to adjust the pH to 4.0~5.0, stir for 15 minutes, filter, wash the filter cake with water until neutral, and vacuum dry to obtain 1.23 g of white solid, yield 87.9% .
[0126] ESI-MS[M+H] + : m / z 315.4
[0127] 1 H NMR (400MHz, DMSO-d 6 )δppm: 10.17(s,1H,CONH),9.73(s,1H,CONH),9.23(s,1H,OH),6.68~7.83(m,8H,Ar-H),1.48(s,4H,CH 2 CH 2 ).
Embodiment 3
[0129] N 2 -Benzyl-4-chloro-N 2 -Synthesis of phenylpyridine-2,3-diamine (intermediate 5-1)
[0130] Dissolve 2,4-dichloropyridin-3-amine (1.63g, 10mmol) and N-benzylaniline (2.38g, 13mmol) in 30mL of ethanol: water (V / V, 1:6), and add Concentrated hydrochloric acid 0.5mL, heated to 100 ° C, reflux reaction for 8h. After the reaction, cool to room temperature, a white solid precipitates, filter with suction, wash the filter cake with water, add saturated NaHCO 3 : EtOAc (V / V, 1:1) mixed solution 140mL. After stirring for 30 minutes, the layers were separated, and the organic layer was washed with saturated sodium chloride solution, dried, filtered, and concentrated to obtain 1.78 g of off-white solid with a yield of 57.4%. The product does not need to be purified and can be directly used for the next reaction.
[0131] ESI-MS[M+H] + : m / z 310.4
[0132] 1 H NMR (400MHz, DMSO-d 6 )δppm: 8.02(d,1H,J=8Hz,pyridine-5-H),6.85~7.79(m,11H,Ar-H),5.25(s,2H,NH 2 ),4.51(s,2H,CH ...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More