Synthetic method of 2-subsituted quinazoline compounds

A synthesis method and compound technology, applied in the synthesis of nitrogen-containing heterocyclic compounds and the synthesis of 2-substituted quinazoline compounds, can solve the problems of low yield and purity, difficult to obtain raw materials, high price, etc.

Inactive Publication Date: 2013-09-04
THE SECOND HOSPITAL AFFILIATED TO WENZHOU MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] Although there are multiple synthetic methods of the above-mentioned 2-substituted quinazoline compounds in the prior art, there are certain defects in these methods, such as raw materials are difficult to obtain

Method used

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  • Synthetic method of 2-subsituted quinazoline compounds
  • Synthetic method of 2-subsituted quinazoline compounds
  • Synthetic method of 2-subsituted quinazoline compounds

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0073] Example 1: Synthesis of 2-phenylquinazoline

[0074]

[0075] In a dry and clean four-port reactor, add 50ml solvent acetonitrile, and then add the above formula (II) compound, formula (III) compound, CuCl, Ce(NO 3 ) 3 , Ammonium chloride, KOH, make the molar ratio of 1:1:0.05:0.05:1:1, wherein the compound of formula (II) is 10mmol. The reaction system was reacted at 60°C for 30 hours, during which oxygen was continuously bubbled in.

[0076] After the reaction, the solvent was removed from the mixture obtained after the reaction with a rotary evaporator, and the residue was purified by 200 silica gel column chromatography to obtain the target product with a yield of 97.5% and a purity of 98.9% (HPLC).

[0077] Melting point: 97-98°C.

[0078] NMR: 1 H NMR(DMSO-d 6 ,500MHz)δ9.71(s,1H),8.56-8.59(m,2H),8.17(d,J=8.0Hz,1H),8.01-8.08(m,2H),7.72-7.77(m,1H) ,7.56-7.59(m,3H);

[0079] 13 C NMR(DMSO-d 6 , 125MHz): δ161.2, 159.7, 149.9, 137.5, 134.8, 130.4, 128.6 (2C), 128.0, 127.8 (2C)...

Example Embodiment

[0080] Example 2: Synthesis of 2-(4-fluorophenyl)quinazoline

[0081]

[0082] In a dry and clean four-port reactor, add 45ml solvent acetonitrile, and then add the above formula (II) compound, formula (III) compound, CuCl, Ce(NO 3 ) 3 ·6H 2 O, ammonium sulfate, KOH, make the molar ratio of 1:1.5:0.1:0.1:1.5:1.5, wherein the compound of formula (II) is 10 mmol. The reaction system was reacted at 70°C for 26 hours, during which oxygen was continuously bubbled in.

[0083] After the reaction, the solvent was removed from the mixture obtained after the reaction with a rotary evaporator, and the residue was purified by 300 silica gel column chromatography to obtain the target product with a yield of 99.2% and a purity of 99.5% (HPLC).

[0084] Melting point: 135-137°C.

[0085] NMR: 1 H NMR(CDCl 3 ,500MHz)δ9.43(s,1H),8.60-8.64(m,2H),8.06(d,J=8.3Hz,1H),7.89(t,J=8.1Hz,2H),7.60(t,J =7.2Hz,1H),7.20(t,J=8.4Hz,2H);

[0086] 13 C NMR(CDCl 3 ,125MHz):δ164.7(d, 1 J C-F =245.1Hz,1C),160.6,160.2,15...

Example Embodiment

[0087] Example 3: Synthesis of 2-(2-methylphenyl)quinazoline

[0088]

[0089] In a dry and clean four-port reactor, add 50ml solvent acetonitrile, and then add the above formula (II) compound, formula (III) compound, CuCl, CeCl 3 , Ammonium chloride, KOH, make the molar ratio of 1:2:0.15:0.15:2:2, wherein the compound of formula (II) is 10mmol. The reaction system was reacted at 80°C for 22 hours, during which oxygen was continuously bubbled in.

[0090] After the reaction, the solvent was removed from the mixture obtained after the reaction with a rotary evaporator, and the residue was purified by 400 silica gel column chromatography to obtain the target product as a viscous oil with a yield of 97.6% and a purity of 98.6% (HPLC).

[0091] NMR: 1 H NMR(CDCl 3 ,500MHz)δ9.50(s,1H),8.10(d,J=8.3Hz,1H),7.89-7.94(m,2H),7.77(d,J=7.6Hz,1H),7.63(t,J =7.6Hz,1H),7.45(t,J=7.5Hz,1H),7.06-7.11(m,2H),3.86(s,3H);

[0092] 13 C NMR(CDCl 3 , 125MHz): δ162.5, 159.9, 157.6, 150.5, 134.0, 131.7, 130.7,...

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Abstract

The invention relates to a synthetic method of 2-subsituted quinazoline compounds. In the synthetic method, copper compounds and cerium compounds are adopted to serve as bi-component catalysts, and the 2-subsituted quinazoline compounds are prepared by reacting 2-aminobenzyl alcohols with aromatic aldehyde compounds in organic solvents in the presence of ammonium sources. The synthetic method is easy to operate, high in product yield and purity, is a novel synthetic method for preparation of the 2-subsituted quinazoline compounds, and has a good industrial prospect and potential application value.

Description

technical field [0001] The invention relates to a synthesis method of nitrogen-containing heterocyclic compounds, in particular to a synthesis method of 2-substituted quinazoline compounds, belonging to the field of organic chemical synthesis. Background technique [0002] Among the various nitrogen-containing heterocyclic compounds, quinazoline compounds have wide application and research prospects in the fields of medicine and pesticides because of their good biological activity. [0003] Quinazoline compounds have a strong inhibitory effect on epidermal growth factor receptor (EGFR) and tyrosine kinase (EGFR-TK), and can be used for anticancer. In addition, quinazoline compounds have many medical applications such as bactericidal, insecticidal, antiviral, anti-inflammatory, antihypertensive, and anti-tuberculosis. At the same time, some quinazoline compounds have become commercialized drugs, such as the anticancer drug Gefi Tini, the bactericidal drug propoxyquinoline, e...

Claims

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Application Information

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IPC IPC(8): C07D239/74C07D409/04C07D405/04C07D239/72B01J23/83
Inventor 叶乐平李昌崇朱雪琼苏苗赏张园海余刚
Owner THE SECOND HOSPITAL AFFILIATED TO WENZHOU MEDICAL COLLEGE
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