CN106518789B - A method of synthesis Quinazol derivative - Google Patents
A method of synthesis Quinazol derivative Download PDFInfo
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- CN106518789B CN106518789B CN201510587495.7A CN201510587495A CN106518789B CN 106518789 B CN106518789 B CN 106518789B CN 201510587495 A CN201510587495 A CN 201510587495A CN 106518789 B CN106518789 B CN 106518789B
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- 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
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
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- 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
-
- 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
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention discloses a kind of methods for synthesizing quinazolinone, the present invention is from anthranilamide, in water as solvent, ring expansion occurs with benzaldehyde, generates dihydro quinoline azoles woods ketone intermediate, then in the presence of metal iridium complex, dehydrogenation obtains Quinazol derivative, reaction shows three significant advantages: 1) reaction carries out in aqueous solution, reduces being applicable in for a large amount of organic solvents, water is cheap, green, safe solvent；2) reaction is avoided using highly toxic oxidant, avoids damaging environment；2) it is by-product, non-environmental-pollution that reaction, which generates hydrogen,；Therefore, which meets the requirement of Green Chemistry, has vast potential for future development.
Description
Technical field
The invention belongs to technical field of organic synthetic chemistry, and in particular to a kind of preparation method of Quinazol derivative.
Background technique
Quinazolinone represents the structural framework of a kind of prevalence, they are present in more than 150 kinds of alkaloids, such as
Rutaecarppine,Luotonin A,Luotonin F,Sildenafil,Bouchardatine and Raltirexed。
(For selected reviews,see:S.B.Mhaske,N.P.Argade,Tetrahedron,2006,62,9787–
9826.(b)I.Khan,A.Ibrar,N.Abbas,A.Saeed,Eur.J.Med.Chem.2014,76,193-1944:Kung,
P.P.；Casper,M.D.；Cook,K.L.；Wilson-Lingard,L.；Risen,L.M.；Vickers,T.A.；Ranken,
R.；Blyn,L.B.；Wyatt,R.；Cook,P.D.；Ecker,D.J.J.Med.Chem.1999,42,4705-4713).
Quinazolinone also has extensive bioactivity, such as antimycotic, antiviral, anti-inflammatory, anti-spasm, anticancer performance
(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.Lett.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.X.Liu and Q.M.Wang,
Eur.J.Med.Chem.,2012,53,275-282；Laszlo,S.E.；Quagliato,C.S.；Greenlee,W.J.；
Patchett,A.A.；Chang,R.S.L.；Lotti,V.J.；Chen,T.B.；Scheck,S.A.；Faust,K.A.；
Kivlighn,S.S.；Schorn,T.S.；Zingaro,G.J.；Siegl,P.K.S.J.Med.Chem.1993,36,3207-
3210；M.M.Aly,Y.A.Mohamed,K.A.El-Bayouki,W.M.Basyouni,S.Y.Abbas,
Eur.J.Med.Chem.,2010,45,3365-3373；Kobayashi,S.；Ueno,M.；Suzuki,R.；Ishitani,
H.Tetrahedron Lett.1999,40,2175-2178；Cao,S.L.；Feng,Y.P.；Jiang,Y.Y.；Liu,S.Y.；
Ding,G.Y.；Li,R.T.Bioorg.Med.Chem.Lett.2005,15,1915-1917.)
The tradition of Quinazol derivative and general synthetic method are former as starting by anthranilamide and aldehyde
After material reaction generates intermediate dihydroquinazoline ketone, by oxidizing synthesis.However, these methods often need to use and work as
The toxic oxidising agent of amount, such as KMnO4,MnO2,CuCl,DDQ,I2,t-BuOOH and PhI(OAc)2, and generate a large amount of
By-product, seriously pollute environment.Moreover, these reactions usually carry out in organic solvent, it is also possible to pollute environment.((a)
Hisano,T.；Ichikawa,M.；Nakagawa,A.；Tsuji,M.Chem.Pharm.Bull.1975,23,1910-1916.
(b)Balakumar,C.；Lamba,P.；Kishore,D.P.；Narayana,B.L.；Rao,K.V.；Rajwinder,K.；
Rao,A.R.；Shireesha,B.；Narsaiah,B.Eur.J.Med.Chem.2010,45,4904-4913.(c)Mitobe,
Y.；Ito,S.；Mizutani,T.；Nagase,T.；Sato,N.；Tokita,S.Bioorg.Med.Chem.Lett.2009,
19,4075-4078.(d)Abdel-Jalil,R.J.；Voelter,W.；Saeed,M.Tetrahedron Lett.2004,45,
3475-3476.)。
From the angle of sustainable chemistry, develop a kind of water-soluble metal-organic complex catalyst to realize in water
Dehydrogenation reaction is carried out, avoids synthesizing quinazolinone using oxidant participation significant.
Summary of the invention
The purpose of the present invention is to provide a kind of synthetic methods of Quinazol derivative.
The present invention is achieved through the following technical solutions: synthesis Quinazol derivative (formula I)
It is by anthranilamide (Formula II)
It is reacted with compound aldehyde (formula III)
Reaction obtains intermediate (formula IV)
Then catalytic dehydrogenation synthesizes in the presence of water-soluble iridium metal complexes.
Its reaction formula is
Wherein, R1Selected from single or multiple substitution alkyl, halogen, preferably methyl, dimethoxy, fluorine, chlorine, bromine.
R2A substituent group is represented, alkyl, preferably butyl, cyclohexyl or single or multiple substituted aryl, single or multiple substitution are selected from
The preferred aminomethyl phenyl of aryl, methoxyphenyl, isopropyl phenyl, trifluoromethyl, Trifluoromethoxyphen-l, halogenophenyl,
Naphthalene, thienyl.
The new method that the present invention synthesizes quinazolinone is realized by following specific steps:
Anthranilamide, compound aldehyde and solvent H is added in step 1, in the reaction vessel2O；Reaction mixture
After reacting a few hours at a reflux temperature, it is cooled to room temperature；
Water-soluble iridium metal complexes, after reaction mixture reacts a few hours again at a reflux temperature, rotation are added in step 2
Dry solvent obtains target compound then by post separation.
In step 1, the dosage of the compound aldehyde is the 1.0equiv. of anthranilamide mole.
In step 1, the reaction time is 2 hours.
In step 2, the water-soluble iridium metal complexes be [Cp*Ir (bpy) Cl] Cl (bpy=2,2 '-
bipyridine)(cat.1)、[Cp*Ir(H2O)3][OTf]2(cat.2)、[Cp*Ir(H2O)3][BF4]2(cat.3), [Cp*Ir
(H2O)3][PF6]2(cat.4), [Cp*Ir (H2O)3][SO4] (cat.5) and [Cp*Ir (NH3)3][Cl]2(cat.6) any in
It is a kind of.
In step 2, the dosage of water-soluble iridium metal complexes is the 1mol% of anthranilamide；When the described reaction
Between be 1 hour.
Compared with the existing technology, anthranilamide of the present invention sets out, and in water as solvent, ring expansion occurs with benzaldehyde
Reaction generates dihydro quinoline azoles woods ketone intermediate, and then in the presence of metal iridium complex, dehydrogenation obtains Quinazol derivative,
Reaction shows three significant advantages: 1) reaction carries out in aqueous solution, reduces being applicable in for a large amount of organic solvents, water is honest and clean
The solvent of valence, green, safety；2) reaction is avoided using highly toxic oxidant, avoids damaging environment；2) reaction life
It is by-product, non-environmental-pollution at hydrogen；Therefore, which meets the requirement of Green Chemistry, has vast potential for future development.
Specific embodiment
It shows that example illustrates certain embodiments of the present invention, and should not be construed as limiting the scope of the invention.It is right
Present disclosure can carry out many improvement, changes and modifications from material, method and reaction condition simultaneously.It is all this
A little to improve, changes and modifications are definitely fallen within the spirit and scope of the present invention.
Embodiment 1:2- phenylquinazoline -4 (3H) -one
2-phenylquinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), benzaldehyde (106mg, 1mmol), water (1mL) is sequentially added 5mL
In single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3][OTf]2
(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes solvent, so
Pure target compound is obtained by column chromatography (solvent: ethyl acetate/n-hexane) afterwards, yield: 90%.
1H NMR(500MHz,CDCl3) δ 11.58 (s, br, 1H, NH), 8.34 (d, J=7.8Hz, 1H, ArH), 8.26
(dd,J1=3.1Hz, J2=6.7Hz, 2H, ArH), 7.80-7.85 (m, 2H, ArH), 7.59-7.60 (m, 3H, ArH), 7.51
(t, J=7.3Hz, 1H, ArH)；13C{1H}NMR(125MHz,CDCl3):δ163.9,151.8,149.5,134.9,132.8,
131.6,129.0,128.0,127.4,126.7,126.3,120.9.
- 4 (3H) -one of embodiment 2:2- o-methyl-phenyl quinazoline
2-(o-Tolyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), o-tolualdehyde (120mg, 1mmol), water (1.0mL) is successively
It is added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 87%.
1H NMR(500MHz,DMSO-d6) δ 12.44 (s, br, 1H, NH), 8.16 (d, J=5.9Hz, 1H, ArH), 7.84
(s, 1H, ArH), 7.69 (d, J=6.2Hz, 1H, ArH), 7.50-7.54 (m, 2H, ArH), 7.43 (s, 1H, ArH), 7.34 (s,
2H,ArH),2.38(s,3H,CH3)；13C{1H}NMR(125MHz,DMSO-d6):δ161.8,154.3,148.7,136.1,
134.4,134.2,130.5,129.8,129.1,127.3,126.6,125.8,125.7,121.0,19.5.
- 4 (3H) -one of embodiment 3:2- p-methylphenyl quinazoline
2-(p-Tolyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), p-tolyl aldehyde (120mg, 1mmol), water (1mL) successively adds
Into 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 85%.
1H NMR(500MHz,CDCl3): δ 11.48 (s, br, 1H, NH), 8.33 (d, J=7.8Hz, 1H, ArH), 8.15
(d, J=7.8Hz, 2H, ArH), 7.78-7.83 (m, 2H, ArH), 7.49 (t, J=7.0Hz, 1H, ArH), 7.38 (d, J=
7.8Hz,2H,ArH),2.46(s,3H,CH3)；13C{1H}NMR(125MHz,CDCl3):δ164.0,151.8,149.6,142.1,
134.8,130.0,129.7,127.9,127.4,126.5,126.3,120.8,21.5.
Embodiment 4:2- (3,4- 3,5-dimethylphenyl) quinazoline -4 (3H) -one
2-(3,4-dimethylphenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), 3,4- dimethylbenzaldehydes (134mg, 1mmol), water (1.0mL)
It is sequentially added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir is added
(H2O)3][OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression
Solvent is removed, pure target compound is then obtained by column chromatography (solvent: ethyl acetate/n-hexane), yield:
86%.
1H NMR(500MHz,DMSO-d6): δ 12.40 (s, br, 1H, NH), 8.14 (d, J=7.5Hz, 1H, ArH), 8.01
(s, 1H, ArH), 7.92 (d, J=7.2Hz, 1H, ArH), 7.82 (t, J=6.9Hz, 1H, ArH), 7.73 (d, J=7.8Hz,
1H, ArH), 7.50 (t, J=7.0Hz, 1H, ArH), 7.30 (d, J=7.4Hz, 1H, ArH), 2.31 (s, 3H, CH3),2.30
(s,3H,CH3)；13C{1H}NMR(125MHz,DMSO-d6):δ162.2,152.3,148.8,140.2,136.6,134.5,
130.1,129.6,128.6,127.3,126.3,125.8,125.1,120.8,19.4,19.3.
Embodiment 5:2- (4- isopropyl phenyl) quinazoline -4 (3H) -one
2-(4-isopropylphenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), cumaldehyde (148mg, 1mmol), water (1.0mL) according to
It is secondary to be added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir is added
(H2O)3][OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression
Solvent is removed, pure target compound is then obtained by column chromatography (solvent: ethyl acetate/n-hexane), yield:
82%.
1H NMR(500MHz,DMSO-d6):δ12.48(s,br,1H,NH),8.12-8.15(m,3H,ArH),7.83(t,J
=7.5Hz, 1H, ArH), 7.73 (d, J=7.7Hz, 1H, ArH), 7.51 (t, J=7.0Hz, 1H, ArH), 7.42 (d, J=
7.3Hz,2H,ArH),2.96-2.99(m,1H,CH(CH3)2), 1.24 (d, J=7.0Hz, 6H, 2xCH3)；13C{1H}NMR
(125MHz,DMSO-d6):δ162.3,152.2,152.1,148.8,134.5,130.3,127.8,127.4,126.5,
126.4,125.8,120.9,33.4,23.6.
- 4 (3H) -one of embodiment 6:2- p-methoxyphenyl quinazoline
2-(4-methoxyphenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), P-methoxybenzal-dehyde (136mg, 1mmol), water (1.0mL) according to
It is secondary to be added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir is added
(H2O)3][OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression
Solvent is removed, pure target compound is then obtained by column chromatography (solvent: ethyl acetate/n-hexane), yield:
91%.
1H NMR(500MHz,DMSO-d6): δ 12.41 (s, br, 1H, NH), 8.19 (d, J=8.4Hz, 2H, ArH), 8.13
(d, J=7.6Hz, 1H, ArH), 7.81 (t, J=7.3Hz, 1H, ArH), 7.70 (d, J=8.0Hz, 1H, ArH), 7.48 (t, J
=7.3Hz, 1H, ArH), 7.09 (d, J=8.3Hz, 2H, ArH), 3.85 (s, 3H, OCH3)；13C{1H}NMR(125MHz,
DMSO-d6):δ162.3,161.8,151.8,148.9,134.5,129.4,127.3,126.1,125.8,124.8,120.7,
113.9,55.4.
Embodiment 7:2- (3,4- Dimethoxyphenyl) quinazoline -4 (3H) -one
2-(3,4-dimethoxyphenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), Veratraldehyde (166mg, 1mmol), water
(1.0mL) is sequentially added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then it is added
[Cp*Ir(H2O)3][OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Very
Solvent is removed under reduced pressure in sky, then obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), produces
Rate: 86%.
1H NMR(500MHz,DMSO-d6): δ 12.44 (s, br, 1H, NH), 8.13 (d, J=7.6Hz, 1H, ArH), 7.87
(d, J=8.1Hz, 1H, ArH), 7.81-7.83 (m, 2H, ArH), 7.72 (d, J=8.1Hz, 1H, ArH), 7.49 (t, J=
7.4Hz, 1H, ArH), 7.12 (d, J=8.4Hz, 1H, ArH), 3.88 (s, 3H, OCH3),3.85(s,3H,OCH3)；13C{1H}
NMR(125MHz,DMSO-d6):δ162.3,151.8,151.6,148.9,148.5,134.5,127.3,126.1,125.8,
124.7,121.1,120.7,111.3,110.7,55.7(2OCH3).
- 4 (3H) -one of embodiment 8:2- o-fluorophenyl quinazoline
2-(2-fluorophenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), o fluorobenzaldehyde (124mg, 1mmol), water (1.0mL) successively adds
Into 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then metal iridium catalyst is added
(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes solvent, so
Pure target compound is obtained by column chromatography (solvent: ethyl acetate/n-hexane) afterwards, yield: 78%.
1H NMR(500MHz,DMSO-d6): δ 12.58 (s, br, 1H, NH), 8.17 (d, J=7.8Hz, 1H, ArH), 7.86
(t, J=7.4Hz, 1H, ArH), 7.79 (t, J=7.1Hz, 1H, ArH), 7.73 (d, J=8.1Hz, 1H, ArH), 7.63 (q, J
=6.6Hz, 1H, ArH), 7.57 (t, J=7.5Hz, 1H, ArH), 7.36-7.41 (m, 2H, ArH)；13C{1H}NMR(125MHz,
DMSO-d6):δ161.5,159.6(d,JC-F=249.1Hz), 149.9,148.7,134.6,132.8 (d, JC-F=8.3Hz),
131.0,127.5,127.0,125.8,124.6,122.3(d,JC-F=12.7Hz), 121.1,116.1 (d, JC-F=
21.0Hz).
- 4 (3H) -one of embodiment 9:2- Chloro-O-Phenyl quinazoline
2-(2-chlorophenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), o-chlorobenzaldehyde (141mg, 1mmol), water (1.0mL) successively adds
Into 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 82%.
1H NMR(500MHz,DMSO-d6): δ 12.63 (s, br, 1H, NH), 8.18 (d, J=7.4Hz, 1H, ArH), 7.86
(t, J=6.9Hz, 1H, ArH), 7.71 (d, J=7.8Hz, 1H, ArH), 7.67 (d, J=6.9Hz, 1H, ArH), 7.62 (d, J
=7.6Hz, 1H, ArH), 7.58 (t, J=7.4Hz, 2H, ArH), 7.50 (t, J=7.4Hz, 1H, ArH)；13C{1H}NMR
(125MHz,DMSO-d6):δ161.4,152.2,148.5,134.5,133.8,131.6,131.5,130.8,129.6,
127.4,127.2,127.0,125.8,121.2.
- 4 (3H) -one of embodiment 10:2- rubigan quinazoline
2-(4-chlorophenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), p-chlorobenzaldehyde (141mg, 1mmol), water (1.0mL) successively adds
Into 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 87%.
1H NMR(500MHz,DMSO-d6): δ 12.59 (s, br, 1H, NH), 8.20 (d, J=7.6Hz, 2H, ArH), 8.15
(d, J=7.1Hz, 1H, ArH), 7.84 (t, J=6.4Hz, 1H, ArH), 7.74 (d, J=7.7Hz, 1H, ArH), 7.62 (d, J
=7.6Hz, 2H, ArH), 7.55 (t, J=6.6Hz, 1H, ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ162.1,
151.3,148.5,136.3,134.6,131.5,129.6,128.6,127.5,126.7,125.8,121.0.
- 4 (3H) -one of embodiment 11:2- p-bromophenyl quinazoline
2-(4-bromophenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), p-bromobenzaldehyde (185mg, 1mmol), water (1.0mL) successively adds
Into 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 78%.
1H NMR(500MHz,DMSO-d6):δ12.60(s,br,1H,NH),8.12-8.16(m,3H,ArH),7.84(t,J
=7.1Hz, 1H, ArH), 7.74-7.77 (m, 3H, ArH), 7.53 (t, J=7.1Hz, 1H, ArH)；13C{1H}NMR(125MHz,
DMSO-d6):δ162.1,151.5,148.5,134.6,131.9,131.6,129.8,127.5,126.7,125.8,125.2,
121.0.
- 4 (3H) -one of embodiment 12:2- p-trifluoromethyl phenyl quinazoline
2-(4-(trifluoromethyl)phenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), p-trifluoromethyl benzaldehyde (174mg, 1mmol), water (1.0mL)
It is sequentially added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir is added
(H2O)3][OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression
Solvent is removed, pure target compound is then obtained by column chromatography (solvent: ethyl acetate/n-hexane), yield:
81%.
1H NMR(500MHz,DMSO-d6): δ 12.75 (s, br, 1H, NH), 8.37 (d, J=7.8Hz, 2H, ArH), 8.18
(d, J=7.5Hz, 1H, ArH), 7.93 (d, J=7.8Hz, 2H, ArH), 7.87 (t, J=7.4Hz, 1H, ArH), 7.78 (d, J
=7.9Hz, 1H, ArH), 7.57 (t, J=7.5Hz, 1H, ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ162.1,
(151.1,148.4,136.6,134.7,131.1 q, J=31.9Hz), 128.7,127.6,127.0,125.8,125.4 (d, J
=3.0Hz), 123.9 (q, J=270.7Hz), 121.2.
Embodiment 13:2- is to Trifluoromethoxyphen-l quinazoline -4 (3H) -one
2-(4-(trifluoromethoxy)phenyl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), to trifluoro-methoxybenzaldehyde (190mg, 1mmol), water
(1.0mL) is sequentially added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then it is added
[Cp*Ir(H2O)3][OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Very
Solvent is removed under reduced pressure in sky, then obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), produces
Rate: 78%.
1H NMR(500MHz,DMSO-d6): δ 12.65 (s, br, 1H, NH), 8.30 (d, J=8.7Hz, 2H, ArH), 8.16
(d, J=7.8Hz, 1H, ArH), 7.85 (t, J=7.6Hz, 1H, ArH), 7.75 (d, J=8.1Hz, 1H, ArH), 7.53-7.56
(m,3H,ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ162.1,151.1,148.4,136.6,134.6,131.1(q,
JC-F=31.9Hz), 128.7,127.6,127.0,125.8,125.4,123.9 (d, JC-F=255.8Hz), 121.1.
Embodiment 14:2- (1- naphthalene) quinazoline -4 (3H) -one
2-(naphthalen-1-yl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), 1- naphthaldehyde (156mg, 1mmol), water (1.0mL) is sequentially added
In 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 85%.
1H NMR(500MHz,DMSO-d6): δ 12.67 (s, br, 1H, NH), 8.22 (d, J=7.7Hz, 1H, ArH), 8.17
(d, J=7.6Hz, 1H, ArH), 8.12 (d, J=8.1Hz, 1H, ArH), 8.05 (d, J=7.3Hz, 1H, ArH), 7.87 (t, J
=7.2Hz, 1H, ArH), 7.80 (d, J=6.7Hz, 1H, ArH), 7.74 (d, J=7.9Hz, 1H, ArH), 7.65 (t, J=
7.6Hz,1H,ArH),7.57-7.62(m,3H,ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ161.8,153.6,
148.7,134.5,133.1,131.7,130.3,130.2,128.3,127.6,127.4,127.0,126.7,126.3,
125.8,125.2,125.0,121.2.
Embodiment 15:2- (2- naphthalene) quinazoline -4 (3H) -one
2-(naphthalen-2-yl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), 2- naphthaldehyde (156mg, 1mmol), water (1.0mL) is sequentially added
In 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 81%.
1H NMR(500MHz,DMSO-d6): δ 12.67 (s, br, 1H, NH), 8.82 (s, 1H, ArH), 8.31 (d, J=
8.4Hz, 1H, ArH), 8.19 (d, J=7.6Hz, 1H, ArH), 8.07 (t, J=7.1Hz, 1H, ArH), 8.02 (d, J=
7.2Hz, 1H, ArH), 7.86 (t, J=7.2Hz, 1H, ArH), 7.80 (d, J=7.9Hz, 1H, ArH), 7.61-7.67 (m, 2H,
), ArH 7.55 (t, J=7.2Hz, 1H, ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ162.18,152.19,148.75,
134.59,134.09,132.25,129.92,128.91,128.12,128.06,127.86,127.61,127.52,126.86,
126.60,125.86,124.46,121.02.
Embodiment 16:2- (2- thienyl) quinazoline -4 (3H) -one
2-(thiophen-2-yl)quinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), 2 thiophene carboxaldehyde (112mg, 1mmol), water (1.0mL) successively adds
Into 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 77%.
1H NMR(500MHz,DMSO-d6): δ 12.66 (s, br, 1H, NH), 8.82 (s, 1H, ArH), 8.12 (d, J=
7.1Hz, 1H, ArH), 7.87 (d, J=3.2Hz, 1H, ArH), 7.80 (t, J=7.3Hz, 1H, ArH), 7.65 (d, J=
7.3Hz, 1H, ArH), 7.49 (t, J=7.2Hz, 1H, ArH), 7.24 (s, ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ
161.8,148.6,147.8,137.4,134.6,132.1,129.4,128.5,126.9,126.3,126.0,120.9.
Embodiment 17:2- (phenylethyl) quinazoline -4 (3H) -one
2-phenethylquinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), benzenpropanal (134mg, 1mmol), water (1.0mL) is sequentially added
In 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 84%.
1H NMR(500MHz,DMSO-d6): δ 12.26 (s, br, 1H, NH), 8.08 (d, J=7.1Hz, 1H, ArH), 7.78
(t, J=6.9Hz, 1H, ArH), 7.62 (d, J=7.8Hz, 1H, ArH), 7.46 (t, J=7.1Hz, 1H, ArH), 7.28 (s,
4H, ArH), 7.19 (s, 1H, ArH), 3.05 (t, J=7.5Hz, 2H, CH2), 2.89 (t, J=7.6Hz, 2H, CH2)；13C{1H}
NMR(125MHz,DMSO-d6):δ161.74,156.54,148.84,140.73,134.25,128.31,126.79,126.04,
125.97,125.67,120.83,36.30,32.44.
- 4 (3H) -one of embodiment 18:2- n-propyl quinazoline
2-propylquinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), n-butanal (72mg, 1mmol), water (1.0mL) is sequentially added 5mL
In single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3][OTf]2
(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes solvent, so
Pure target compound is obtained by column chromatography (solvent: ethyl acetate/n-hexane) afterwards, yield: 81%.
1H NMR(500MHz,DMSO-d6): δ 12.16 (s, br, 1H, NH), 8.07 (d, J=7.8Hz, 1H, ArH), 7.76
(t, J=7.4Hz, 1H, ArH), 7.59 (d, J=8.1Hz, 1H, ArH), 7.45 (t, J=7.4Hz, 1H, ArH), 2.57 (t, J
=7.5Hz, 2H, CH2),1.71-1.78(m,2H,CH2), 0.93 (t, J=7.3Hz, 3H, CH3)；13C{1H}NMR(125MHz,
DMSO-d6):δ161.8,157.3,148.9,134.2,126.8,125.9,125.6,120.8,36.3,20.2,13.4.
- 4 (3H) -one of embodiment 19:2- cyclohexyl quinazoline
2-cyclohexylquinazolin-4(3H)-one
By anthranilamide (136mg, 1mmol), hexahydrobenzaldehyde (112mg, 1mmol), water (1.0mL) successively adds
Into 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 81%.
1H NMR(500MHz,DMSO-d6): δ 12.08 (s, br, 1H, NH), 8.07 (d, J=7.9Hz, 1H, ArH), 7.76
(t, J=7.6Hz, 1H, ArH), 7.59 (d, J=8.2Hz, 1H, ArH), 7.44 (t, J=7.5Hz, 1H, ArH), 2.57 (tt, J
=11.8Hz, J=3.3Hz, 1H, CH), 1.78-1.91 (m, 4H, CH2),1.54-1.69(m,3H,CH2),1.18-1.34(m,
3H,CH2)；13C{1H}NMR(125MHz,DMSO-d6):δ161.9,160.7,148.9,134.2,126.9,125.8,125.6,
120.9,42.8,30.2,25.5,25.3.
- 4 (3H) -one of embodiment 20:6- methyl -2- phenylquinazoline
6-methyl-2-phenylquinazolin-4(3H)-one
By 2- amino -5- methyl benzamide (150mg, 1mmol), benzaldehyde (106mg, 1mmol), water (1.0mL) according to
It is secondary to be added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir is added
(H2O)3][OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression
Solvent is removed, pure target compound is then obtained by column chromatography (solvent: ethyl acetate/n-hexane), yield:
81%.
1H NMR(500MHz,DMSO-d6): δ 12.45 (s, br, 1H, NH), 8.17 (d, J=7.3Hz, 2H, ArH), 8.04
(d, J=8.0Hz, 1H, ArH), 7.53-7.60 (m, 4H, ArH), 7.34 (d, 1H, J=8.0Hz, 1H, ArH), 2.47 (s, 3H,
CH3)；13C{1H}NMR(125MHz,DMSO-d6):δ162.1,152.3,148.8,145.0,132.8,131.3,128.5,
128.0,127.7,127.0,125.7,118.6,21.3.
- 4 (3H) -one of embodiment 21:6,7- dimethoxy -2- phenylquinazoline
6,7-dimethoxy-2-phenylquinazolin-4(3H)-one
By 2- amino -4,5- dimethoxybenzarnide (196mg, 1mmol), benzaldehyde (106mg, 1mmol), water
(1.0mL) is sequentially added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then it is added
[Cp*Ir(H2O)3][OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Very
Solvent is removed under reduced pressure in sky, then obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), produces
Rate: 78%.
1H NMR(500MHz,DMSO-d6): δ 12.40 (s, br, 1H, NH), 8.16 (d, J=7.3Hz, 2H, ArH),
7.48-7.55(m,4H,ArH),7.21(s,1H,ArH),3.93(s,3H,OCH3),3.89(s,3H,OCH3)；13C{1H}NMR
(125MHz,DMSO-d6):δ161.5,154.7,150.8,148.6,144.8,132.8,131.0,128.5,127.4,
114.0,108.2,105.0,55.9,55.7.
Fluoro- 2- phenylquinazoline -4 (3H) -one of embodiment 22:5-
5-fluoro-2-phenylquinazolin-4(3H)-one
By 2- amino -6- fluorobenzamide (154mg, 1mmol), benzaldehyde (106mg, 1mmol), water (1.0mL) is successively
It is added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 84%.
1H NMR(500MHz,DMSO-d6): δ 12.55 (s, br, 1H, NH), 8.17 (d, J=6.8Hz, 2H, ArH),
7.82-7.78 (m, 1H, ArH), 7.62-7.55 (m, 4H, ArH), 7.26 (d, J=9.1Hz, 1H, ArH)；13C{1H}NMR
(125MHz,DMSO-d6): δ 161.6,159.5 (d, J=9.1Hz), 153.3,150.8,135.1 (d, J=9.1Hz),
(132.2,131.6,128.6,127.8,123.5,112.9 d, J=20.2Hz), 110.4.
Fluoro- 2- phenylquinazoline -4 (3H) -one of embodiment 23:6-
6-fluoro-2-phenylquinazolin-4(3H)-one
By 2- amino-5-fluorine benzamide (154mg, 1mmol), benzaldehyde (106mg, 1mmol), water (1.0mL) is successively
It is added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 81%.
1H NMR(500MHz,DMSO-d6):δ12.69(s,br,1H,NH),8.25-8.23(m,2H,ArH),7.76-
7.69(m,2H,ArH),7.58(dt,J1=8.7Hz, J=2.8Hz, 1H, ArH), 7.50-7.47 (m, 3H, ArH)；13C{1H}
NMR(125MHz,DMSO-d6): δ 165.0,159.2 (d, J=241.9Hz), 155.2,146.7,135.5,130.3,129.5
(d, J=7.7Hz), 128.2,127.7,122.3 (d, J=7.5Hz), 121.6,121.4.
Fluoro- 2- phenylquinazoline -4 (3H) -one of embodiment 24:7-
7-fluoro-2-phenylquinazolin-4(3H)-one
By 2- amino -4- fluorobenzamide (154mg, 1mmol), benzaldehyde (106mg, 1mmol), water (1.0mL) is successively
It is added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 75%.
1H NMR(500MHz,DMSO-d6):δ12.60(s,br,1H,NH),8.20-8.14(m,3H,ArH),8.15(d,J
=7.30Hz, 2H, ArH), 7.60 (t, J=6.85Hz, 1H, ArH), 7.55 (t, J=7.13Hz, 2H, ArH), 7.49 (d, J=
9.60Hz, 1H, ArH), 7.37 (t, J=8.03Hz, 1H, ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ165.9(d,J
=250.0Hz), 161.7,153.9,151.0 (d, J=12.5Hz), 132.5,131.7,129.0 (d, J=10.0Hz),
(128.7,128.0,118.0,115.2 d, J=23.8Hz), the 112.4 chloro- 2- phenyl of (d, J=21.2Hz) embodiment 25:6-
Quinazoline -4 (3H) -one
6-chloro-2-phenylquinazolin-4(3H)-one
By 2-Amino-5-chlorobenzamide (171mg, 1mmol), benzaldehyde (106mg, 1mmol), water (1.0mL) is successively
It is added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 84%.
1H NMR(500MHz,DMSO-d6): δ 12.71 (s, br, 1H, NH), 8.17 (d, J=7.1Hz, 2H, ArH), 8.09
(s, 1H, ArH), 7.86 (d, J=8.0Hz, 1H, ArH), 7.76 (d, J=8.6Hz, 1H, ArH), 7.54-7.62 (m, 3H,
ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ161.3,152.8,147.4,134.6,132.4,131.5,130.7,
129.7,128.6,127.8,124.8,122.2.
Chloro- 2- phenylquinazoline -4 (3H) -one of embodiment 26:7-
7-chloro-2-phenylquinazolin-4(3H)-one
By 2- amino -4- chlorobenzamide (171mg, 1mmol), benzaldehyde (106mg, 1mmol), water (1.0mL) is successively
It is added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%), after reacting 1 hour under reflux temperature, it is cooled to room temperature.Vacuum decompression removes
Then solvent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 85%.
1H NMR(500MHz,DMSO-d6): δ 12.67 (s, br, 1H, NH), 8.17 (d, J=7.5Hz, 2H, ArH), 8.14
(d, J=8.5Hz, 1H, ArH), 7.79 (m, 1H, ArH), 7.61 (t, J=7.1Hz, 1H, ArH), 7.54-7.57 (m, 3H,
ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ161.3,152.8,147.4,134.6,132.4,131.5,130.7,
129.7,128.6,127.8,124.8,122.2.
Bromo- 2- phenylquinazoline -4 (3H) -one of embodiment 27:5-
5-bromo-2-phenylquinazolin-4(3H)-one
By 2- amino -6- brombenzamide (215mg, 1mmol), benzaldehyde (106mg, 1mmol), water (1.0mL) is successively
It is added in 5mL single port bottle.After mixture reacts 2 hours at a reflux temperature, it is cooled to room temperature.Then [Cp*Ir (H is added2O)3]
[OTf]2(6.8mg, 0.01mmol, 1mol%) is cooled to room temperature after reacting 1 hour under reflux temperature.Vacuum decompression removes molten
Then agent obtains pure target compound by column chromatography (solvent: ethyl acetate/n-hexane), yield: 75%.
1H NMR(500MHz,DMSO-d6):δ12.56(s,br,1H,NH),8.18-8.16(m,2H,ArH),7.73(q,J
=1.3Hz, 1H, ArH), 7.71 (dd, J1=3.5Hz, J2=1.2Hz, 1H, ArH), 7.66-7.59 (m, 2H, ArH), 7.55
(tt,J1=7.5Hz, J2=1.5Hz, 2H, ArH)；13C{1H}NMR(125MHz,DMSO-d6):δ160.5,152.7,151.1,
134.6,132.6,132.1,131.6,128.5,127.8,127.7,120.1,118.8.HRMS-EI(70eV)m/z cacld
for C14H8BrN2O[M-H]298.9820,found 298.9827.
Embodiment 28
Except with [Cp*Ir (bpy) Cl] Cl (5.6mg, 0.01mmol, 1mol%) replace [Cp*Ir (H2O)3][OTf]2
(6.8mg, 0.01mmol, 1mol%), other reaction raw materials, condition and product are the same as embodiment 1, yield 83%
Embodiment 29
Except with [Cp*Ir (H2O)3][BF4]2(6.7mg, 0.01mmol, 1mol%) replaces [Cp*Ir (H2O)3][OTf]2
(6.8mg, 0.01mmol, 1mol%), other reaction raw materials, condition and product are the same as embodiment 1, yield 80%
Embodiment 30
Except with [Cp*Ir (H2O)3][PF6]2(6.7mg, 0.01mmol, 1mol%) replaces [Cp*Ir (H2O)3][OTf]2
(6.8mg, 0.01mmol, 1mol%), other reaction raw materials, condition and product are the same as embodiment 1, yield 85%
Embodiment 31
Except with [Cp*Ir (H2O)3][SO4] (4.8mg, 0.01mmol, 1mol%) replacement [Cp*Ir (H2O)3][OTf]2
(6.8mg, 0.01mmol, 1mol%), other reaction raw materials, condition and product are the same as embodiment 1, yield 82%
Embodiment 32
Except with [Cp*Ir (NH3)3][Cl]2(4.5mg, 0.01mmol, 1mol%) replaces [Cp*Ir (H2O)3][OTf]2
(6.8mg, 0.01mmol, 1mol%), other reaction raw materials, condition and product are the same as embodiment 1, yield 85%.
Claims (4)
1. a kind of method for synthesizing Quinazol derivative, which is characterized in that the derivative is to pass through anthranilamide
II
It is reacted with compound aldehyde III
Reaction obtains intermediate compound IV
Then catalytic dehydrogenation synthesizes in the presence of water-soluble iridium metal complexes, obtains target product I,
Wherein, R1A substituent group is represented, methyl, dimethoxy, fluorine, chlorine or bromine are selected from；
R2A substituent group is represented, butyl, cyclohexyl, aminomethyl phenyl, methoxyphenyl, isopropyl phenyl, trifluoromethylbenzene are selected from
Base, Trifluoromethoxyphen-l, halogenophenyl, naphthalene or thienyl；
Specifically prepare according to the following steps:
Anthranilamide, compound aldehyde and solvent H is added in step 1, in the reaction vessel2O；Reaction mixture is flowing back
At a temperature of react a few hours after, be cooled to room temperature；
Water-soluble iridium metal complexes are added in step 2, after reaction mixture reacts a few hours again at a reflux temperature, are spin-dried for molten
Agent obtains target compound then by post separation, wherein the water-soluble iridium metal complexes are [Cp*Ir (bpy)
Cl]Cl、[Cp*Ir(H2O)3][OTf]2、[Cp*Ir(H2O)3][BF4]2、[Cp*Ir(H2O)3][PF6]2、[Cp*Ir(H2O)3]
[SO4] and [Cp*Ir (NH3)3][Cl]2In any one.
2. the method for synthesis Quinazol derivative as described in claim 1, which is characterized in that in step 1, the chemical combination
The dosage of object aldehyde is the 1.0equiv. of anthranilamide mole.
3. the method for synthesis Quinazol derivative as described in claim 1, which is characterized in that in step 1, the reaction
Time is 2 hours.
4. the method for synthesis Quinazol derivative as described in claim 1, which is characterized in that in step 2, water-soluble iraurite
The dosage for belonging to complex compound is the 1mol% of anthranilamide；The reaction time is 1 hour.
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| CN107793367B (en) * | 2016-08-29 | 2020-06-19 | 南京理工大学 | Method for synthesizing human microsomal prostaglandin synthetase 1 inhibitor FR20 |
| CN109420525B (en) * | 2017-08-21 | 2021-10-08 | 南京理工大学 | Metal iridium catalyst of 2, 2' -bis-benzimidazole ligand and method for synthesizing N-methylated primary amine by using metal iridium catalyst |
| CN109879820B (en) * | 2019-02-26 | 2022-07-19 | 扬州大学 | Synthetic method of quinazolinone heterocyclic compound |
| CN111875549B (en) * | 2020-08-11 | 2023-04-28 | 许昌学院 | Method for synthesizing quinazolinone compound in aqueous phase through photocatalysis |
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| WO2009158404A1 (en) * | 2008-06-26 | 2009-12-30 | Resverlogix Corp. | Methods of preparing quinazolinone derivatives |
| CN102503986A (en) * | 2011-11-09 | 2012-06-20 | 南京邮电大学 | Phosphorescence iridium complex, preparation method and organic electroluminescent device |
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| WO2009158404A1 (en) * | 2008-06-26 | 2009-12-30 | Resverlogix Corp. | Methods of preparing quinazolinone derivatives |
| CN101970416A (en) * | 2008-06-26 | 2011-02-09 | 雷斯韦洛吉克斯公司 | Methods of preparing quinazolinone derivatives |
| CN102503986A (en) * | 2011-11-09 | 2012-06-20 | 南京邮电大学 | Phosphorescence iridium complex, preparation method and organic electroluminescent device |
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