4-phenoxy quinoline sulfonylurea compound, intermediate for synthesizing compound, and preparation method and application of compound
A technology of phenoxyquinoline and sulfonylureas, which is applied in organic chemistry, drug combination, antineoplastic drugs, etc., and achieves the effects of simple synthesis process, novel structure and good application prospects
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[0047] 1. The preparation of intermediate II compound: the nitro compound is obtained by the nucleophilic substitution reaction of p-nitrophenol or 2-fluoro-4-nitrophenol to the halogenated compound, and then obtained by reducing the nitro group. The specific reaction formula is as follows :
[0048]
[0049] Where: R 1 is selected from methyl, butyl, 3-morpholinopropyl, 3-(piperidin-1-yl)propyl, 3-(tetrahydropyrrol-1-yl)propyl; X is selected from hydrogen or fluorine.
[0050] 2. Preparation of intermediate III compound: react differently substituted benzyl chlorides and thiourea under ethanol reflux conditions for 3 to 5 hours, then evaporate the solvent under reduced pressure, add an appropriate amount of acetonitrile to dissolve, and cool to 0 o After C, N-chlorosuccinimide is added to obtain benzylsulfonyl chloride, which is reacted with ammonia to obtain sulfonamide, which is then reacted with ethyl chloroformate to obtain ethyl sulfonamidoformate, specifically The ...
Embodiment 1
[0063] Preparation compound: 1-[4-(6,7-dimethylquinoline-4-oxyl)phenyl]-3-(benzylsulfonyl)urea
[0064]
[0065] Step a: Synthesis of 6,7-dimethoxy-4-(4-nitrophenyloxy)quinoline, the reaction formula is as follows:
[0066]
[0067] Take 4-chloro-6,7-dimethoxyquinoline (671 mg, 3.0 mmol) and 4-nitrophenol (500 mg, 3.6 mmol ) in 7 mL of chlorobenzene, slowly heat to 140 o C, continue to react at this temperature for 20 h. Then stop heating, cool to room temperature, evaporate the solvent under reduced pressure, dissolve the residue with dichloromethane, wash with saturated potassium carbonate solution and water successively, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify by silica gel column chromatography (PE / EA=3:1), 620 mg of light yellow solid was obtained, and the yield was 63%.
[0068] Step b: 4-[(6,7-Dimethoxy)quinoline-4-oxyl]aniline
[0069]
[0070] Weigh 6,7-dimethoxy-4-(4-nitrophenyl)quinoline (620 mg, 1.9 mmol) and d...
Embodiment 2
[0074] Example 2: Preparation of 1-[4-(6,7-dimethylquinoline-4-oxyl)phenyl]-3-[(4-fluorobenzyl)sulfonyl]urea
[0075]
[0076] The experimental procedure was the same as that in Example 1, except that ethyl p-fluorobenzylsulfonamide formate was used instead of ethyl benzylsulfonamide formate. White solid, yield: 46.4%. MP: 159-161 o c. 1 H NMR (400 MHz, DMSO- d 6 ) δ 8.94(s, 1H),8.48(d, J = 5.2 Hz, 1 H), 7.59 (d, J = 8.8 Hz, 1 H), 7.51 (s, 1 H), 7.43-7.39 (m, 3 H), 7.27-7.23 (m, 4 H), 6.46 (d, J = 5.2 Hz, 1 H), 4.77 (s, 2 H), 3.94 (s, 3 H), 3.93 (s, 3 H).
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