Synthesis method of quinazolin-4(3H)-ketone

A technology for synthesizing quinazoline and heterocyclic compounds is applied in the synthetic field of preparing quinazoline-4-ketone-ones) heterocyclic compounds, which can solve problems such as toxicity and difficult operation, and achieve simple process, short reaction time, Response applies a wide range of effects

Inactive Publication Date: 2014-09-03
BEIJING INSTITUTE OF TECHNOLOGYGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Li et al. have developed a method for preparing quinazolin-4(3H)-one analogs under palladium catalysis using o-aminobenzonitrile, CO and halogenated aromatic hydrocarbons as raw materials. The CO used in this method is poisonous and the reaction is Gas-liquid reaction under pressure, difficult to operate (Green Chem.,2014,16:1336)

Method used

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  • Synthesis method of quinazolin-4(3H)-ketone
  • Synthesis method of quinazolin-4(3H)-ketone
  • Synthesis method of quinazolin-4(3H)-ketone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Add 1mmol 2-iodobenzonitrile, 1.2mmol benzamide, 10ml N-methylpyrrolidone into a 25ml three-necked flask, add 2mmol sodium hydroxide under stirring, then add 0.05mmol cuprous iodide, and stir the mixture for 10h , after the reaction was completed, the reaction solution was poured into 25ml of ice-water mixture, a mixture of oil and solid was separated out, and the product was separated by column chromatography, ethyl acetate: petroleum ether (1:2, v:v), to obtain 2- Phenyl-quinazolin-4(3H)-one, yield 86%, m.p.240-242°C. The reaction formula of 2-iodobenzonitrile and benzamide is:

[0022]

[0023] The spectral data of product (1) is: IR(KBr, v, cm -1 ):3194,3167,3061,1668,1602,1481; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):12.57(s,1H),8.20-8.16(m,3H),7.85(t,J=15.2Hz,1H),7.75(d,J=7.2Hz,6H),7.62-7.52 (m,4H); 13 C NMR (100MHz, DMSO-d 6 )(δ,ppm):162.25,152.30,148.75,134.59,132.71,131.38,128.60(2C),127.76(2C),127.50,126.58,125.84,120.98; MS(ESI)m / z(%):222.9( [M+H] + ,10...

Embodiment 2

[0025]Add 1mmol 2-bromobenzonitrile, 1.2mmol acetamide, 10ml N-methylpyrrolidone into a 25ml three-necked flask, add 2mmol sodium hydroxide under stirring, then add 0.05mmol cuprous iodide, and stir the mixture for 10h. After the reaction was completed, the reaction solution was poured into 25ml of ice-water mixture, and a mixture of oil and solid was separated out, and the product was separated by column chromatography, ethyl acetate:petroleum ether (2:1, v:v), to obtain 2-ethyl ether yl-quinazolin-4(3H)-one, yield 74%, m.p.236-237°C. The reaction formula of 2-bromobenzonitrile and acetamide is:

[0026]

[0027] The spectral data of product (2) is: IR(KBr, v, cm -1 ):3170,3120,2869,1681,1615,1468; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):12.20(s,1H),8.06(d,J=8.0Hz,1H),7.77-7.73(m,1H),7.56(d,J=8.4Hz,1H),7.44(t ,J=14.8Hz,1H),2.34(s,1H); 13 C NMR (100MHz, DMSO-d 6 )(δ,ppm):161.69,154.25,148.98,134.27,126.58,125.85,125.67,120.61,21.42; MS(ESI)m / z(%):161.0([M+H] + ,100).

Embodiment 3

[0029] Propionamide was used instead of acetamide, and the others were the same as in Example 2 to obtain the target compound (3) in a yield of 72%, m.p.230-232°C. The reaction formula of 2-bromobenzonitrile and propionamide is:

[0030]

[0031] The spectral data of product (3) is: IR(KBr, v, cm -1 ):3169,3111,2980,1679,1620,1468; 1 H NMR (400MHz, DMSO-d 6 )(δ,ppm):12.16(s,1H),8.07(d,J=8.0Hz,1H),7.79-7.75(m,1H),7.59(d,J=8.0Hz,1H),7.45(t ,J=14.4Hz,1H),2.65-2.59(m,2H),1.24(t,J=14.8Hz,3H); 13 CNMR (100MHz, DMSO-d 6 )(δ,ppm):162.26,158.77,149.43,134.69,127.27,126.35,126.14,121.30,28.30,11.73; MS(ESI)m / z(%):175.0([M+H] + ,100).

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Abstract

The invention provides a synthesis method of quinazolin-4(3H)-ketone heterocyclic compound. A general reaction formula is as shown in the specification, wherein R1 is a substituent group and can be H, F, NO2, alkyl or alkoxy; X is halogen and can be Cl, Br or I; R2 is H, alkyl, aryl or heteroaryl. A catalyst used in reaction is copper salt and can be cuprous iodide, cuprous chloride, cuprous oxide, cuprous acetate or the like; the used alkaline is inorganic alkaline or organic alkaline and can be sodium (potassium) hydroxide, potassium carbonate, potassium phosphate, cesium fluoride, cesium carbonate, DBU or the like. Conventional heating or microwave acceleration can be adopted in a reaction implementing process; purification is realized by using a recrystallization or column chromatographical separation means. The synthesis method is easily available in raw materials, simple in process, mild in reaction condition, wide in reaction application range and capable of synthesizing various quinazolin-4(3H)-ketone heterocyclic compounds at one step by using different substrates.

Description

(1) Technical field [0001] The invention relates to a synthesis method for preparing quinazoline-4(3H)-ones (quinazoline-4(3H)-ones) heterocyclic compounds through the reaction of 2-halogenated benzonitrile and its derivatives with amides. (2) Background technology [0002] Quinazoline-4(3H)-ketones are a class of important nitrogen-containing heterocyclic compounds, which have a wide range of biological activities, such as anticancer (Chem.Rev., 2003,103(3):893), antitumor (Tetrahedron, 2006,62(42):9787), antihypertensive (Tetrahedron, 2005,61(43):10153), anti-inflammatory, anti-tuberculosis (Curr.Org.Chem., 2003,7(7):659 ), antifungal, etc. In addition, quinazolin-4(3H)-one is also the skeleton of many natural products and marketed drugs, such as cameline A, B, E and F are all important classes of compounds isolated from the Chinese medicinal plant Artemisia camel. Natural quinazoline-4(3H)-one alkaloids can be used to treat cough, asthma, swelling, rheumatic arthralgia ...

Claims

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Application Information

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IPC IPC(8): C07D239/91C07D239/90
CPCC07D239/90C07D239/91
Inventor李加荣柴洪新杨留攀史大昕张奇
OwnerBEIJING INSTITUTE OF TECHNOLOGYGY