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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

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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 (such as o-aminobenzylamine is difficult to synthesize, expensive), need precious metals, The reaction route is too cumbersome, the yield and purity are low, the reaction conditions are harsh and need fine control, etc.

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
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Effect test

Embodiment 1

[0073] Embodiment 1: the synthesis of 2-phenylquinazoline

[0074]

[0075] In a dry and clean four-port reactor, add 50ml of solvent acetonitrile, then add the above formula (II) compound, formula (III) compound, CuCl, Ce(NO 3 ) 3 , ammonium chloride, KOH, so that the molar ratio is 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....

Embodiment 2

[0080] Embodiment 2: the synthesis of 2-(4-fluorophenyl) quinazoline

[0081]

[0082] In a dry and clean four-port reactor, add 45ml of solvent acetonitrile, then add the above formula (II) compound, formula (III) compound, CuCl, Ce(NO 3 ) 3 ·6H 2 O, ammonium sulfate, KOH, so that the molar ratio is 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...

Embodiment 3

[0087] Embodiment 3: the synthesis of 2-(2-tolyl) quinazoline

[0088]

[0089] In a dry and clean four-port reactor, add 50ml of solvent acetonitrile, then add the above formula (II) compound, formula (III) compound, CuCl, CeCl 3 , ammonium chloride, KOH, so that its molar ratio is 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 ended, 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...

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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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