Alkoxybiphenyl α, β-unsaturated amide compound, its preparation method and medical application
A technology of amide compounds and alkoxybiphenyls, which can be used in the fields of medicinal chemistry and pharmacotherapeutics, and can solve problems such as inapplicability
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0124] 5'-(1-carbonyl)imidazole-7,7'-dimethoxy-4,4'-dibenzo[d][1,3]dioxole]-5-carboxylic acid methyl ester ( VI)
[0125] Biphenyl double fat (30g) was dispersed with 300mL of 10% sodium hydroxide, and the temperature was raised to 120°C to reflux. After reacting for about 8 hours, the reaction solution was clear, and a small amount of solid was removed by suction filtration. The filtrate was adjusted to pH 2-3 with concentrated hydrochloric acid to produce a white solid, and about 26 g of white solid Intermediate II was obtained by suction filtration. The above-mentioned intermediate II was dissolved in about 150 mL of acetic anhydride, the temperature was raised to 150°C and refluxed, reacted for about 10 h, and the acetic anhydride was removed by rotary evaporation to obtain about 25 g of yellow oily intermediate III. Add about 150mL of methanol to the above product, raise the temperature to reflux at 90°C, and react for about 3h to obtain about 23.3g of intermediate IV wi...
Embodiment 2
[0129] Methyl 5'-formyl-7,7'-dimethoxy-4,4'-dibenzo[d][1,3]dioxol-5-carboxylate (VII)
[0130] Compound VI (1.5g, 3.8mmol) was placed in a constant pressure dropping funnel, and 30mL of CH 2 Cl 2 Dissolve, then slowly drop into the CH of PCC (900mg, 4.2mmol) 2 Cl 2 In the suspension (cooled in an ice bath), after the dropwise addition, return to room temperature and stir for reaction. TLC followed the reaction process. After the reaction, the reaction solution was filtered with diatomaceous earth (or silica gel), and the filtrate was concentrated to dryness to obtain a crude product. Separation and purification by flash silica gel column chromatography (PE / EtOAc=3:1, V / V) gave white intermediate VII (1.46 g, 98%). This compound is a known compound. (Bioorganic & Medicinal Chemistry 20 (2012) 2540–2548). m.p.179-181°C; 1 H-NMR (CDCl 3 ,300MHz,δppm):3.68(s,3H,COOCH 3 ),3.98(s,3H,ArOCH 3 ),3.99(s,3H,ArOCH 3 ),6.01-6.10(m,4H,2×OCH 2 O),7.32(s,1H,Ar-H),7.42(s,1H,Ar-H); ...
Embodiment 3
[0132] (E)-5'-(3-(2-methoxyphenyl)amino-3-oxo-1-propenyl)-7,7'-dimethoxy-4,4'-dibenzo [d][1,3]Dioxolyl-5-carboxylic acid methyl ester (1a)
[0133] Intermediate VII (500mg, 1.3mmol) and malonic acid (400mg, 3.8mmol) were mixed, 1ml of DMF and pyridine (210μl) were added, stirred at room temperature for about half an hour, then transferred to an oil bath at 115°C, and bubbles appeared. The reaction progress was tracked by TLC. After the reaction was completed, extraction was performed with ethyl acetate, and the organic layer was washed with dilute hydrochloric acid, water, and saturated brine, and dried over anhydrous sodium sulfate. Concentrate under reduced pressure to obtain a crude product. Purification by flash silica gel column chromatography (PE / EtOAc=5:3-1:1, V / V) gave white compound VIII (360 mg) with a yield of 65%.
[0134] Compound VIII (200mg, 0.47mmol), EDCI (100mg, 0.5mmol), DMAP (60mg, 0.5mmol), o-methoxyaniline (150mg, 0.94mmol) were mixed and dissolved in abo...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More