CN107337646B - Method for synthesizing quinazolinone derivative by using methanol as raw material - Google Patents
Method for synthesizing quinazolinone derivative by using methanol as raw material Download PDFInfo
- Publication number
- CN107337646B CN107337646B CN201610284502.0A CN201610284502A CN107337646B CN 107337646 B CN107337646 B CN 107337646B CN 201610284502 A CN201610284502 A CN 201610284502A CN 107337646 B CN107337646 B CN 107337646B
- Authority
- CN
- China
- Prior art keywords
- methanol
- arh
- reaction
- anthranilamide
- synthesizing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
Abstract
The invention discloses a method for synthesizing quinazolinone derivatives by using methanol as a raw material, which comprises the steps of adding anthranilamide derivative II, methanol III and iridium metal complex into a reaction container, reacting the reaction mixture in a microwave reactor or under magnetic stirring at 130 +/-10 ℃ for more than 2 hours, cooling to room temperature, spin-drying the solvent, and then separating by a column to obtain the target compound. The reaction of the invention adopts nontoxic and renewable methanol as raw material, and the reaction generates hydrogen and water as byproducts, thereby having no environmental pollution, meeting the requirement of green chemistry and having wide development prospect.
Description
Technical Field
The invention belongs to the technical field of organic synthetic chemistry, and particularly relates to a method for synthesizing quinazolinone derivatives by using methanol as a raw material.
Background
Quinazolinones represent a class of popular structural backbones that are present in a wide variety of 150 alkaloids, such as Febrifugine, Fiscalin B (-) -circumstatin H/J (R ═ H/OMe), and trimiquazoline C. (Forselected reviews, see (a) Mhaske, S.B.; Argade, N.P.tetrahedron 2006,62,9787.(b) Khan, I.; Ibrar, A.; Abbas, N.; Saeed, A.Eur.J.Med.chem.2014,76,193).
Quinazolinones also have a wide range of biological activities, such as antifungal, antiviral, anti-inflammatory, anti-spasmodic, anti-cancer properties (Liverton, N.J.; Armstrong, D.J.; Claremon, D.A.; Remy, D.C.; Baldwin, J.J.; Lynch, R.J.; Zhang, G.; Gould, R.J. bioorg.Med.Chem.Lele.1998, 8,483-487, Z.W.Wang, M.X.Wang, X.Yao, Y.Li, J.Tan, L.Z.Wang, W.T.Qiao, Y.Q.Geng, Y.Med.Liu and Q.M.Wang, Eur.J.Chem, 53,275, Lasz.S.J.J.J.J.Chen.J.Chen.K.;.S.S. K. Cheng, U.S.S. K. Cheng, K. Cheng, K. Shen, K. No. 7, K. Cheng. Cheng, K. Cheng, K. Cheng, K. Cheng, K. Cheng, K. Cheng, K. Cheng, K. Cheng, K. Cheng, K. Cheng, K. Cheng
The traditional and general synthetic method of the quinazolinone derivative is that o-aminobenzoic acid (or ester) and formamide are used as starting materials and are generated under severe reaction conditions, and by-products with high molecular weight are generated, so that the environment is polluted, and the atom economy of the reaction is low. (a) VanBrocklin, H.F.; Lim, J.K.; cofening, S.L.; Hom, D.L.; Negash, K.; Ono, M.Y.; Gilmore, J.L.; Bryant, I.; Riese, D.J.J.Med.Chem.2005,48,7445.(b) Gao, L.; Kovackova, S. 2015; Sala, M.; Ramadori, A.T.; Jonghe, S.D.; Herwijn, P.J.Med.Chem.2014,57,7624.(c) Micky, Y.Z.; Torrella, D.; Liao, J.; Qin, X.; Chen J.J.; Gulley.J.J.J.Cheo, J.J.J.J.J. J. Torrent.J. Torrent.52. Cheq.J. J. J. 6,1086. T. Cheo.
Disclosure of Invention
The present invention aims to provide a method for synthesizing quinazolinone derivatives using methanol as a raw material.
The invention is realized by the following technical scheme: a method for synthesizing quinazolinone derivatives (formula I) using methanol as raw material,
is prepared by anthranilamide derivatives (formula II)
With methanol (formula III)
The catalyst iridium metal complex participates in the catalytic dehydrogenation oxidation reaction to obtain the catalyst,
wherein R is1Selected from methyl, methoxy, halogen, trifluoromethyl;
R2hydrogen or butyl is chosen.
The reaction formula is
The method for synthesizing the quinazolinone derivative is realized by the following specific steps:
adding anthranilamide derivative II, methanol III and iridium metal complex into a reaction container, reacting the reaction mixture in a microwave reactor or under magnetic stirring at 130 +/-10 ℃ for more than 2 hours, cooling to room temperature, spin-drying the solvent, and then separating by a column to obtain the target compound.
Further, the iridium metal complex is [ Cp Ir (2, 2' -bpyO) (H)2O)]Or [ Cp Ir (6,6- (OH)2bpy)(H2O)][OTf]2
[Cp*Ir(6,6-(OH)2bpy)(H2O)][OTf]2[Cp*Ir(2,2’-bpyO)(H2O)]。
Further, iridium metal complex is used in an amount of 1 mol% based on anthranilamide.
Further, the molar amount of the base is 0.3 to 1equiv based on the molar amount of the anthranilamide.
Further, the molar amount of methanol was 4equiv based on the molar amount of anthranilamide.
Compared with the prior art, the invention has two remarkable advantages: 1) the raw material used in the reaction is methanol, the methanol is a rich and renewable resource, and the methanol can be prepared from petroleum, natural gas, biomass and CO2 in the atmosphere; 2) hydrogen and water generated by the reaction are byproducts, so that no environmental pollution is caused; therefore, the reaction meets the requirement of green chemistry and has wide development prospect.
Drawings
FIG. 1 is a schematic diagram of the reaction mechanism of the present invention.
Detailed Description
The following examples are shown to illustrate certain embodiments of the present invention and should not be construed as limiting the scope of the invention. Many modifications, variations and changes in materials, methods and reaction conditions may be made simultaneously with respect to the disclosure herein. All such modifications, variations and changes are intended to fall within the spirit and scope of the present invention.
The reaction mechanism provided by the invention is shown in figure 1, and two molecules of hydrogen are released to realize the reaction under the action of the metal-ligand bifunctional catalyst.
Example 1 quinazolin-4-one
quinazolin-4(3H)-one
2-aminobenzamide (68mg,0.5mmol) and [ Cp Ir (2, 2' -bpyO) (H2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were added to a dry 5mL microwave reaction tube in that order. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 88 percent
1H NMR(500MHz,DMSO-d6)δ12.26(br s,1H,NH),8.12(d,1H,J＝7.9Hz,ArH),8.09(s,1H,ArH),7.81(t,1H,J＝7.1Hz,ArH),7.67(t,1H,J＝8.1Hz,ArH),7.52(t,1H,J＝7.7Hz,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ160.7,148.7,145.3,134.2,127.2,126.7,125.8,122.6.
Example 2 6-Methylquinazolin-4-one
6-methylquinazolin-4(3H)-one
2-amino-5-methylbenzamide (75mg,0.5mmol) and [ Cp. multidot.Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 90 percent of
1H NMR(500MHz,DMSO-d6)δ12.13(br s,1H,NH),8.02(s,1H,ArH),7.91(s,1H,ArH),7.63(dd,1H,J＝8.3Hz and 1.9Hz,ArH),7.56(d,1H,J＝8.3Hz,ArH),2.44(s,3H,CH3)；13C{1H}NMR(125MHz,DMSO-d6)δ160.9,146.8,144.8,136.4,135.6,127.1,125.2,122.4,20.8.
Example 3 7-Methylquinazolin-4-one
7-methylquinazolin-4(3H)-one
2-amino-4-methylbenzamide (75mg,0.5mmol) and [ Cp. multidot.Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 87 percent of
1H NMR(500MHz,DMSO-d6)δ12.13(br s,1H,NH),8.05(s,1H,ArH),8.00(d,1H,J＝7.8Hz,ArH),7.46(s,1H,ArH),7.33(d,1H,J＝7.5Hz,ArH),2.45(s,3H,CH3)；13C{1H}NMR(125MHz,DMSO-d6)δ160.8,148.9,145.7,144.6,128.0,126.7,125.6,120.2,21.3.
Example 4 6-Methoxyquinazolin-4-one
6-methoxyquinazolin-4(3H)-one
2-amino-5-methoxybenzamide (83mg,0.5mmol) and [ Cp. multidot.Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (DiscoverCEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 91 percent
1H NMR(500MHz,DMSO-d6)δ8.01(s,1H,ArH),7.57(d,1H,J＝8.9Hz,ArH),7.49(d,1H,J＝2.3Hz,ArH),7.36(dd,1H,J＝8.9Hz and 3.3Hz,ArH),3.85(s,3H,CH3)；13C{1H}NMR(125MHz,DMSO-d6):δ162.0,157.4,144.9,143.6,128.6,123.5,123.3,105.7,55.5.
Example 5 6, 7-Dimethoxyquinazolin-4-one
6,7-dimethoxyquinazolin-4(3H)-one
2-amino-4, 5-dimethoxybenzamide (98mg,0.5mmol) and [ Cp Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (DiscoverCEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature.The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 86 percent of the total weight
1H NMR(500MHz,DMSO-d6)δ12.07(br s,1H,NH),7.98(s,1H,ArH),7.44(s,1H,ArH),7.12(s,1H,ArH),3.90(s,3H,OCH3),3.86(s,3H,OCH3)；13C{1H}NMR(125MHz,DMSO-d6)δ160.1,154.4,148.5,144.8,143.8,115.6,108.0,104.9,55.9,55.7.
Example 6-Fluoquinolizin-4-one
6-fluoroquinazolin-4(3H)-one
2-amino-5-fluorobenzamide (77mg,0.5mmol) and [ Cp Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 77 percent
1H NMR(500MHz,DMSO-d6)δ8.09(s,1H,ArH),7.77(dd,1H,J＝8.7Hz and 2.9Hz,ArH),7.73(dd,1H,J＝8.9Hz and 5.2Hz,ArH),7.67(td,1H,J＝8.6Hz and 3.0Hz,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ160.6,159.9(d,JC-F＝243.8Hz),145.7,145.4,129.9(d,JC-F＝7.5Hz),123.9(d,JC-F＝8.8Hz),122.6(d,JC-F＝23.8Hz),110.4(d,JC-F＝22.5Hz).
Example 7 8-Fluoquinazolin-4-one
8-fluoroquinazolin-4(3H)-one
2-amino-3-fluorobenzamide (77mg,0.5mmol) and [ Cp Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 72 percent
1H NMR(500MHz,DMSO-d6)δ12.47(br s,1H,NH),8.14(s,1H,ArH),7.93(d,1H,J＝8.0Hz,ArH),7.68(t,1H,J＝9.3Hz,ArH),7.52-7.48(m,1H,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ162.2,156.4(d,JC-F＝251.5Hz),148.7,138.7(d,JC-F＝10.4Hz),125.8,124.8,121.6,118.7(d,JC-F＝18.3Hz).
Example 8 6-chloroquinazolin-4-one
6-chloroquinazolin-4(3H)-one
2-amino-5-chlorobenzamide (85mg,0.5mmol) and [ Cp. multidot.Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 77 percent
1H NMR(500MHz,DMSO-d6)δ8.13(s,1H,ArH),8.05(d,1H,J＝2.4Hz,ArH),7.83(dd,1H,J＝8.7Hz and 2.4Hz,ArH),7.69(d,1H,J＝8.7Hz,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ160.0,147.5,146.2,134.3,130.9,129.4,124.8,123.9.
Example 9 7-Chloroquinazolin-4-one
7-chloroquinazolin-4(3H)-one
2-amino-4-chlorobenzamide (85mg,0.5mmol) and [ Cp. multidot.Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 70 percent of
1H NMR(500MHz,DMSO-d6)δ12.44(br s,1H,NH),8.13(s,2H,ArH),7.72(s,1H,ArH),7.55(s,1H,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ160.4,149.9,147.2,138.8,127.9,126.9,126.3,121.4.
Example 10 8-Chloroquinazolin-4-one
8-chloroquinazolin-4(3H)-one
2-amino-3-chlorobenzamide (85mg,0.5mmol) and [ Cp. multidot.Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 68 percent of
1H NMR(500MHz,DMSO-d6)δ12.39(br s,1H,NH),8.21(s,1H,ArH),8.08(s,1H,ArH),7.97(s,1H,ArH),7.49(s,1H,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ160.3,146.5,145.2,134.4,130.7,127.0,125.0,124.3.
Example 11 6-Bromoquinazolin-4-one
6-bromoquinazolin-4(3H)-one
2-amino-5-bromobenzamide (107mg,0.5mmol) and [ Cp Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 82 percent of
1H NMR(500MHz,DMSO-d6)δ12.39(br s,1H,NH),8.19(s,1H,ArH),8.14(s,1H,ArH),7.95(d,1H,J＝7.4Hz,ArH),7.62(d,1H,J＝8.6Hz,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ159.7,147.7,146.1,137.0,129.6,127.9,124.2,119.1.
Example 12 Bromoquinazolin-4-one
7-bromoquinazolin-4(3H)-one
2-amino-4-bromobenzamide (107mg,0.5mmol) and [ Cp Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 80 percent of
1H NMR(500MHz,DMSO-d6)δ8.16(d,1H,J＝1.6Hz,ArH),8.14(s,1H,ArH),7.87(dd,1H,J＝8.6Hz and 1.6Hz,ArH),7.56(d,1H,J＝8.6Hz,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ161.7,148.6,148.2,136.2,129.2,127.9,124.3,118.1.
Example 13 7-Trifluoromethylquinazolin-4-one
7-(trifluoromethyl)quinazolin-4(3H)-one
2-amino-4-trifluoromethylbenzamide (102mg,0.5mmol) and [ Cp. multidot.Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. The tubes were protected with nitrogen and placed in a single mode pressure microwave synthesizer (DiscoverCEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 78 percent of
1H NMR(500MHz,DMSO-d6)δ12.55(br s,1H,NH),8.31(d,1H,J＝8.5Hz,ArH),8.23(s,1H,ArH),7.98(s,1H,ArH),7.82(d,1H,J＝7.7Hz,ArH)；13C{1H}NMR(125MHz,DMSO-d6)δ160.1,148.8,147.2,133.9(q,JC-F＝32.2Hz),127.6,125.5,124.3,123.5(q,JC-F＝269.7Hz),122.4.
Example 14 3-Butylquinazolin-4-one
3-butylquinazolin-4(3H)-one
2-amino-N-butylbenzamide (96mg,0.5mmol) and [ Cp Ir (2, 2' -bpyO) (H)2O)](5.4mg,0.005mmol,1 mol%), cesium carbonate (49mg,0.15mmol,0.3equiv.), and methanol (0.5mL) were sequentially added to a dry 5mL microwave reaction tube. Nitrogen protection in microwave tube, single-mode pressure micro-tubeIn the wave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 66 percent
1H NMR(500MHz,DMSO-d6)δ8.32(d,1H,J＝7.5Hz,ArH),8.03(s,1H,ArH),7.76(t,1H,J＝7.3Hz,ArH),7.71(d,1H,J＝8.0Hz,ArH),7.51(t,1H,J＝7.3Hz,ArH),4.01(t,2H,J＝7.3Hz,CH2),1.79(quint,2H,J＝7.5Hz,CH2),1.42(sext,2H,J＝7.4Hz,CH2),0.98(t,3H,J＝7.3Hz,CH3)；13C{1H}NMR(125MHz,DMSO-d6)δ161.1,148.1,146.6,134.1,127.4,127.2,126.7,122.2,46.8,31.4,19.9,13.6.
Example 15 except use of Cs2CO3(0.2equiv), other reaction materials, conditions and products were the same as in example 1, yield was 80%
Example 16 reaction starting materials, conditions and products were the same as in example 1 except that the reaction temperature was 120 ℃ to obtain 78% yield
Example 17 except that K is used2CO3Substitute for Cs2CO3The other reaction raw materials, conditions and products are the same as example 1, and the yield is 83 percent
Example 18 reaction raw materials, conditions and products were the same as example 1 except that the reaction was carried out under magnetic stirring at a reaction temperature of 150 ℃ for 12 hours, and the yield was 66%
Example 19 addition of [ Cp. multidot. Ir (6,6- (OH)2bpy)(H2O)][OTf]2Instead of [ Cp. about. Ir (2, 2' -bpyO) (H)2O)]The other reaction materials, conditions and products were the same as in example 1, and the yield was 82%.
Claims (4)
1. A method for synthesizing quinazolinone derivative I is characterized in that,
is prepared by anthranilamide derivative II
With methanol III
CH3OH
III
The catalyst is obtained by catalytic dehydrogenation oxidation reaction under the participation of iridium metal complex as a catalyst, wherein,
R1selected from methyl, methoxy, halogen, trifluoromethyl;
R2hydrogen or butyl is selected;
the iridium metal complex is [ Cp Ir (2, 2' -bpyO) (H)2O)]Or [ Cp Ir (6,6- (OH)2bpy)(H2O)][OTf]2The structure is as follows:
the method comprises the following specific steps:
adding anthranilamide derivative II, methanol III, alkali and iridium metal complex into a reaction vessel, reacting the reaction mixture in a microwave reactor or under magnetic stirring at 130 +/-10 ℃ for more than 2 hours, cooling to room temperature, spin-drying the solvent, and then separating by a column to obtain the target compound.
2. The method for synthesizing a quinazolinone derivative according to claim 1, wherein the iridium metal complex is used in an amount of 1 mol% based on the anthranilamide.
3. The method for synthesizing a quinazolinone derivative according to claim 1, wherein the molar amount of the base is 0.3-1equiv based on the molar amount of anthranilamide.
4. The method for synthesizing quinazolinone derivative i according to claim 1, wherein the molar amount of methanol is 4equiv based on the molar amount of anthranilamide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610284502.0A CN107337646B (en) | 2016-05-03 | 2016-05-03 | Method for synthesizing quinazolinone derivative by using methanol as raw material |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610284502.0A CN107337646B (en) | 2016-05-03 | 2016-05-03 | Method for synthesizing quinazolinone derivative by using methanol as raw material |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107337646A CN107337646A (en) | 2017-11-10 |
| CN107337646B true CN107337646B (en) | 2020-04-07 |
Family
ID=60221706
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610284502.0A Expired - Fee Related CN107337646B (en) | 2016-05-03 | 2016-05-03 | Method for synthesizing quinazolinone derivative by using methanol as raw material |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107337646B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232418A (en) * | 2013-05-06 | 2013-08-07 | 中国科学技术大学 | Homogeneous catalytic preparation method of gamma-valerolactone |
| CN104418678A (en) * | 2013-08-26 | 2015-03-18 | 南京理工大学 | Method for synthesizing N-alkyl sulfonamide derivative |
-
2016
- 2016-05-03 CN CN201610284502.0A patent/CN107337646B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103232418A (en) * | 2013-05-06 | 2013-08-07 | 中国科学技术大学 | Homogeneous catalytic preparation method of gamma-valerolactone |
| CN104418678A (en) * | 2013-08-26 | 2015-03-18 | 南京理工大学 | Method for synthesizing N-alkyl sulfonamide derivative |
Non-Patent Citations (3)
| Title |
|---|
| Efficient Construction of C=N Double Bonds via Acceptorless Dehydrogenative Coupling;Xiang Sun，等;《Adv. Synth. Catal.》;20130809;第355卷;第2179-2184页 * |
| Efficient syntheses of 2,3-disubstituted natural quinazolinones via iridium catalysis;Jie Fang，等;《Org. Biomol. Chem.》;20120125;第10卷;第2389-2391页，第S2-S3页 * |
| One-Pot Synthesis of Quinazolinones via Iridium-Catalyzed Hydrogen Transfers;Jianguang Zhou，等;《J.Org.Chem.》;20110818;第76卷;第7730-7736页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107337646A (en) | 2017-11-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2012167406A1 (en) | Method for preparing optically pure (+)-ambrisentan and (+)-darusentan | |
| CN104926775A (en) | Preparation method of fluorine-containing pyran derivative | |
| CN102964323A (en) | Synthesis method of 5-(piperazino-1-yl)benzofuryl-2-formamide | |
| CN107337646B (en) | Method for synthesizing quinazolinone derivative by using methanol as raw material | |
| CN107118215B (en) | A kind of preparation method for treating breast cancer medicines Rui Boxini intermediate | |
| CN104860910A (en) | Preparation method of 8-fluoropyran derivative | |
| CN109651367B (en) | Method for preparing 1, 4-dihydroquinoline and pyrrolo [1,2-a ] quinoline compounds | |
| CN105348283B (en) | Synthetic method for tadalafil | |
| CN113698317A (en) | Synthetic method of apatamide, intermediate and synthetic method thereof | |
| CN107337648B (en) | Method for synthesizing erlotinib | |
| CN103554108A (en) | Improved tadalafil preparation method | |
| CN114014805B (en) | Preparation method of trifluoromethyl 2, 4-quinoline diketone compound | |
| CN112209935B (en) | Preparation method of pyrazino-fused quinazolinone substance | |
| CN108484508A (en) | A kind of synthetic method of 5- trifluoromethyl uracils | |
| CN111732516B (en) | A kind ofNProcess for preparing (E) -aryl-substituted heterocyclic compounds | |
| CN111875549B (en) | Method for synthesizing quinazolinone compound in aqueous phase through photocatalysis | |
| CN110218192B (en) | Preparation method of 2-amino-4, 6-dimethoxypyrimidine | |
| CN113336703A (en) | Synthesis of 1,3,4, 5-tetrasubstituted 1H-pyrazole derivatives | |
| CN102993088A (en) | 4-hydroxy-2-pyridone preparation method | |
| CN108409672B (en) | Method for synthesizing polysubstituted pyrimidine under catalysis of copper salt | |
| CN114315746A (en) | 3, 6-bis (dinitromethyl) -1,2,4, 5-tetrazine and synthetic method thereof | |
| CN106916148B (en) | Method for synthesizing brexpiprazole | |
| CN111606910A (en) | Synthesis process of antitumor drug Sapanisiertib | |
| CN114805208A (en) | 4-trifluoromethyl-4, 5-dihydropyrazole derivative and preparation method thereof | |
| Yang et al. | 2-Alkoxy-3, 4-dihydropyrans as modular substrates to construct polyheterocycles by reacting with NH2-containing bisnucleophiles |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200407 |