* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
General procedure: To a stirred solution of amine (0.01 mol) in 10 ml of PEG-300 was added to ethylacetoacatate (0.03 mol) in100 ml round bottom flask and refluxed at 120 C for 1.5–2 h. After completion of the reaction (monitored by TLC) the reaction mixture was cooled and extracted with cold diethyl ether (3 × 10 mL) and purified by column chromatography (10–25percent EtOAc in Hexane) gave the pure product 3a–p. Final products were confirmed with the reported literature.
32%
for 24 h; Reflux; Neat (no solvent)
General procedure: A mixture of ethylacetoacetate 5 (10.0 g, 76.8 mmol) and aniline 6a (7.0 mL, 76.8 mmol) were taken into a round bottom flask and refluxed under stirring for 24 h. The mixture was concentrated under vacuum and then the crude product was purified by column chromatography using EtOAc:hexane to give acetoacetanilide 8a as white crystalline solid in 42percent yield.
Reference:
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2
[ 5394-63-8 ]
[ 104-94-9 ]
[ 5437-98-9 ]
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[ 104-94-9 ]
[ 5437-98-9 ]
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With iron(III) oxide In acetonitrile at 80℃; for 12h; Sealed tube; Green chemistry;
6. General experimental procedure for the synthesis of 2-quinolinones 4aa-ha using β-oxo amides 3aa-ea, ga-ha, ra.
General procedure: A 10 mL reaction vial was charged with β-oxo amides 3aa-ea, ga-ha, ra (1.0 mmol), Fe2O3 (0.1 mmol) and Acetonitrile (1 mL). The reaction vial was then sealed and heated at 80 °C for 12 h. After completion of the reaction (progress was monitored by TLC; SiO2, Hexane/EtOAc = 1:1), the mixture was diluted with ethyl acetate (15 mL) and water (20 mL) and extracted with ethyl acetate (3 × 10 mL). The combined organic layers were washed with brine (3 × 10 mL) and dried over anhydrous Na2SO4. The solvent were removed under reduced pressure and the crude products were purified by column chromatography using silica gel (100-200 mesh) with hexane/EtOAc (1:1) as the eluent to obtain the desired products 4aa-ha.
7-hydroxy-N-(4-methoxyphenyl)-7-methyl-3,5-diphenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-6-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
In ethanol; at 25℃; for 1.5h;Sonication;
General procedure: A mixture of aminoazole 1f-i (1 mmol), acetoacetamides 2a-c (1 mmol), and aromatic aldehyde 3b-f (1 mmol) in 10 mL of ethanol was ultrasonicated at room temperature for 90 min in a round-bottom flask equipped with condenser. The reaction mixture was allowed to stand up to 12 h at room temperature and then was filtered to give the solid compounds 8a-i, which were washed with ethanol and air dried. Reaction products were obtained in high purity and did not require further purification by recrystallization.
Synthesis of derivatives of 4-methylquinolin-2(1H)-one (5 and 6)
The mixture of ethyl acetoacetate (0.1 mol, 13.0 g) and para anisidine (0. 08 mol, 9.85 g) were refluxed with stirring for 20 h. Then the mixture was cooled and poured into Na2CO3 solution. After being extracted with CHCl3, the compound was dried by evaporation in vacuum. Then, 80% sulfuric acid (10 mL) was added drop wise and the reaction mixture was stirred at 95°C. After the reaction finished, the solution was cooled and quenched with ice-water. The crude product was filtered and purified by chromatography to get compound 5 and 6.
With 1-n-butyl-3-methylimidazolim bromide In neat (no solvent) at 120℃; for 1h;
(b) For benzimidazole derivatives
General procedure: A stirred mixture of aromatic diamine (1mmol) and β-ketoester or β-ketoamide (1mmol) was heated under inert condition at 120°C in the presence of 10mol% of ionic liquid III. After completion of reaction as revealed by TLC, product was crystallized from ethyl acetate-hexane or passes through short pad silica-gel to remove any colour impurities from the product to obtain analytically pure benzimidazoles.
4-(2-butyl-4-chloro-1H-imidazol-5-yl)-N-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
With hydrogenchloride; In ethanol;Reflux;
General procedure: A mixture of N-(aryl)-3-oxobutanamides (0.01 mol), 2-butyl-4-chloro-1H-imidazole-5 carbaldehyde (0.01 mol), urea (0.015 mol) and catalytic amount of concentrated hydrochloric acid in ethanol (30 ml) was heated under reflux condition for 20 to 22 hrs. The reaction mixture was kept at room temperature for 24 hrs. The product obtained was isolated and recrystallized from ethanol.
ethyl 5-acetyl-6-hydroxy-2-imino-1-(4-methoxyphenyl)-1,2-dihydropyridine-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
Stage #1: 4'-methoxyacetoacetanilide With sodium ethanolate In ethanol at 20℃; for 1h;
Stage #2: ethyl (ethoxymethylene)cyanoacetate In ethanol for 24h;
Stage #3: With hydrogenchloride; water
Reactions of (ethoxymethylidene)cyanoaceticester 1 with acetoacetamides 2 in the presence of ()triehtylamine or (b) sodium ethoxide
General procedure: a. An ethanol solution of equimolar amounts of compounds 1 and 2 and TEA was heated under reflux for 5 h. The most part of ethanol was then removed by distillation, and the residue was diluted with water. The crystals thatformed were filtered off and washed with alcohol to isolate compounds 4a-4e. The filtrate was evaporated, and the solid residue was dissolved in water. The solution was acidified with HCl, and the crystals that formed were filtered off, washed with water, and dried in air to isolate compounds 5a, 5c, and 5e (see also route b). b. Amide 2-2e was added to a stirred ethanol solution of an equimolar amount of sodium ethoxide (at room temperature) and, after 1 h, an equimolar amount of compound 1 was added to the mixture, and it was allowed to stand for a day at room temperature. The most part of ethanol was removed, and the residue was diluted with water. The crystals that formed were filtered off and washed with alcohol to isolate compounds 4a-4e. The filtrate was evaporated, and the solid residue was dissolved in water. The solution was acidified with HCl, and the crystals that formed were filtered off, washed with water, and dried in air to isolate compound 5a. After removal of water from the filtrate (routes and b), along with chlorides, a viscous material remained, from which no compounds could be isolated.
ethyl 5-(4-methoxyphenylcarbamoyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
36%
With piperidine In ethanol at 20℃;
Ethyl 5-(arylcarbamoyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylates 3a-3h
General procedure: Piperidine, 40 mg (0.5 mmol), was added to a solution of 2.5 mmol of acetoacetanilide 2a-2h and 2.5 mmol of ethyl 2-cyano-3-ethoxyprop-2-enoate (1) in 8 mL of anhydrous ethanol. The mixture was left to stand for 3-4 days at room temperature and concentrated, the residue was treated with diethyl ether, and the precipitate was filtered off, washed with diethyl ether, and dried in air until constant weight. Evaporation of the filtrate left a viscous material from which we failed to isolate any identifiable compound.
Stage #1: N-acetoacetyl-p-methoxyaniline With potassium hydroxide; magnesium(II) chloride In ethanol at 20℃; for 0.5h;
Stage #2: p-toluene isocyanate In ethanol
1; 10-18; 23 Example 1
N-acetoacetyl-p-methoxyaniline (104mg, 0.5 mmol), magnesium chloride (57mg, 0.6 mmol), potassium hydroxide (85% +, 40mg, 0.6 mmol), use 3 mL of ethanol as a solvent, and stir at room temperature for 0.5 hours, Then, p-toluene isocyanate (80 mg, 0.6 mmol) was added, and the reaction process was monitored by TCL. After the reaction was completed, it was evaporated in vacuo The solvent was removed, and the crude product was washed with distilled water for several times to obtain a white solid: 138 mg, with a yield of 93%.The product structure of this embodiment is as follows:
91%
Stage #1: N-acetoacetyl-p-methoxyaniline With potassium hydroxide; magnesium(II) chloride In ethanol at 25℃; for 0.5h; Inert atmosphere;
Stage #2: p-toluene isocyanate In ethanol at 25℃; for 1h; Inert atmosphere;
methyl 4-(3-((4-methoxyphenyl)amino)-3-oxopropanamido)benzoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
89%
Stage #1: N-acetoacetyl-p-methoxyaniline With pyridine; magnesium(II) chloride In dichloromethane at 25℃; for 0.5h; Inert atmosphere;
Stage #2: 4-methoxycarbonylphenyl isocyanate In dichloromethane at 25℃; for 0.5h; Inert atmosphere;
89%
Stage #1: N-acetoacetyl-p-methoxyaniline With potassium hydroxide; magnesium(II) chloride In ethanol at 20℃; for 0.5h;
Stage #2: 4-methoxycarbonylphenyl isocyanate In ethanol
8 Example 8
In a 15mL pressure tube, add N-acetoacetyl-p-methoxyaniline (104mg, 0.5 mmol), magnesium chloride (57mg, 0.6 mmol), potassium hydroxide (85% +, 40mg, 0.6 mmol), use 3 mL of ethanol as a solvent, and stir at room temperature for 0.5 hours, Then add 4-formic acid methyl phenyl isocyanate (97mg, 0.6mmol), use TCL to monitor the reaction process, after the reaction The solvent was removed by rotary evaporation, and the crude product was washed with distilled water for several times to obtain a white solid: 151 mg, and the yield was 89%.The product structure of the present embodiment is as follows: