CA1047967A - Process for preparation of quinazolines - Google Patents
Process for preparation of quinazolinesInfo
- Publication number
- CA1047967A CA1047967A CA228,044A CA228044A CA1047967A CA 1047967 A CA1047967 A CA 1047967A CA 228044 A CA228044 A CA 228044A CA 1047967 A CA1047967 A CA 1047967A
- Authority
- CA
- Canada
- Prior art keywords
- group
- phenyl
- quinazolinone
- reaction
- process according
- 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.)
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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
- C07D409/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C07D239/82—Oxygen atoms with an aryl radical attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- General Chemical & Material Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
Abstract
A PROCESS FOR PREPARATION OF QUINAZOLINES
ABSTRACT OF THE DISCLOSURE
Quinazoline derivatives of the formula, [I]
wherein R1, R2 and R3 are independently a hydrogen atom, a halogen atom, a trifluoromethyl group, a nitro group, a lower alkylsulfonyl group, a lower alkyl group, a lower alkoxy group or a lower alkylthio group; and R4 is a hydrogen atom, a lower alkyl group, an aralkyl group, a lower alkanoyloxyalkyl group, a lower alkoxy-alkyl group, a polyhaloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, a tetrahydrofurfuryl group, a tetrahydropyranylmethyl group, a pyridylmethyl group, a furylmethyl group or a thienylmethyl group, are prepared by irradiating a dihydroquinazolinone derivative of the formula,
ABSTRACT OF THE DISCLOSURE
Quinazoline derivatives of the formula, [I]
wherein R1, R2 and R3 are independently a hydrogen atom, a halogen atom, a trifluoromethyl group, a nitro group, a lower alkylsulfonyl group, a lower alkyl group, a lower alkoxy group or a lower alkylthio group; and R4 is a hydrogen atom, a lower alkyl group, an aralkyl group, a lower alkanoyloxyalkyl group, a lower alkoxy-alkyl group, a polyhaloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, a tetrahydrofurfuryl group, a tetrahydropyranylmethyl group, a pyridylmethyl group, a furylmethyl group or a thienylmethyl group, are prepared by irradiating a dihydroquinazolinone derivative of the formula,
Description
~`
1(~47~a~7 .
1 ~ ~his inven~ion relates to a novel process for preparing quinazoline derivatives.
More particularly, this.invention rela-tes to a novel process for preparing quinazo]ine derivatives o~ the formula, R2 ~ R~ -' `'~
wherein Rl, R2 and R3 are independently a hydrogen atom, a halogen atom, a tri~luoromethyl group, a nitro group, a lower alkylsul~onyl group, a Iower alkyl -- group, a lower alkoxy group or a lower alkylthio ~ :
15 group; and R4 is a hydrogen atom, a lower alkyl group, :.:
.
an~aralkyl group, a lower alkanoyloxyalkyl groupj a lower alkoxyalkyl group, a polyhaloalkyl group, a . cycloalkyl group, a cycloalkylalkyl group, a tetra- ~ ~
hydrofurfuryl group, a tetrahydropyranylmethyl group, ~:
a pyridylmethyl group, a furylmethyl group or a thien~
methyl group.
In the compounds o~ the above ~ormula the term "halogen" includes all.halogen atoms, i.
fluorine~ chlorine, bromine and iodine, the term 25 "alkyl" meanS both straight and branched chain aliphatic ..
hydrocarbon radicals, and lower alkyl i5, ~or example, ;~
Cl_4~alkyl ~7hich includes such groups as methyl, ethyl, ~ . .
. .
n-propyl, isopropyl, n-butyl, isobutyl and tertiary-butyl; the term "lower alkoxy" is 9 for example, C~
~0 alkoxy which includes such ~roups as methoxy, ethoxy, ~. ;
.'.
1~7967 1 n-propoxy, isopropoxy, n-butoxy and tertiary-butoxy;
the term "aralkyl" is, for example, benæyl, phenethyl, phenylpropyl, chlorobenzyl or fluorobenzyl group; the -- term "lower alkylsulfonyl~ i3, f~r example, Cl_4 alkyl-5 sulfonyl which includes such groups as methylsulfonyl, : :~
ethylsulfonyl, propylsulfonyl, etc.; the term "iower alkanoyloxyalkyl" is, for example, (C2_3 alkanoyloxy)-Cl_4 alkyl in which the C2_3 alkànoyloxy moiety in-cludes such groups as acetoxy and propionyloxy, and 10 the Cl_4 alkyl moiety is as defined above; the term ;
"lower alkoxyalkyl" is, ~or example, (Cl_~ alkoxy)-al_4 alkyl in which both moieties are as de~ined - above; the term "polyhaloalkyl" is, for example, a trichloromethyl, trifluoromethyl, trichloroethyl, :
trifluoroethyl or pentafluoropropyl group; the term "cycloalkyl" i~, for examnle, C~ 6 cycloalkyl which includes such groups as cyclopropylj cyclobutyl, cyclo-pentyl, cyclohexyl, methylcyclopropyl, dimethylcyclo- .
propyl, etc.; the term "cycloalkylalkyl" is, for 20 example, (C3_6 cycloalkyl)-Cl_~ alkyl in which both . .
moieties are as defined above; and the term "alkyl-thio" is, ~or example, Cl_4 alkylthio which includes ~uch ~roups as methylthio, ethylthio, propylthio and :~
butylthio. ~: :
~here are some well-known methods for pre- ~ .
paring the quinazoline derivatives represented by the formula [I), and one of the most common methods among them is disclosed in Japanese Patent Publication No. ;~
48396/1972 in ~hich the quinazoline derivatives ~
~0 are obtained by reactin~ a dihydroquinazolinone derivative ~47967 1 of the formula [II~, Rl ~ NH ; (II) 5R2 ~ R3 .
wherein Rl, ~2, R3 and R4 are as defined above, with an oxidizing agent such as potassiwn permangana~e.
The above-mentioned method is, however, relatively troublesome in the operation after the reaction and further includes treatment of the oxidiz-ing agent as waste matter.
, The inventors have studled to overcome the disadvantages of those well-known methods, and found ;~
.
15 ~ that the dihydroquinazolinone derivatives of ~ormula l;
[I~ can be c~nv~rt,e~ t~ the ~uina~ol~none derivàtives of formula [I3 in a high yield by the oxidation reaotion which is caused when the dihydroqulnazolinone deriva~
tives are irradiated with light. In this method, oxidizing agents such as potassium permanganate are not necessary and operation after the reactian is very easy.
Thus, an object of the present inventio~i is to provide quina201ine derivatives o~ the formula tI), which have excellent pharmacological properties.
.
Anothèr object of the present invention;is to provide a novel process ~or producing such useful qui.nazoline ` derivatives. Other objects and~merits of the present invention`will be apparent from the following descrip~
tion.
', ' ' ' .; '''' - 3 ~
'~,. .
~ 7967 .
1 The method of the present invention is carried out by exposin~ the dihydroquinazolinone ~erivatives of the formula (II) to light.
As a light source, sun~i~ht, low-pressure and high-pressure mercury lamps may be used.
The present reaction can advanta~eously be ~-~
carried out in the presence of a solvent. The solvent includes alcohols such as methanol, ethanol an~ iso-propanol, aromatic hydrocarbons such as benzene, ~ ~
10 toluene and xylene, chloroform, acetone, dioxane, ~ ~ ' tetrahydrofuran, dimethylsulfoxide or mixtures there- ~; ;
of. ~he reaction is generally carried out at room temperature, but if necessary it may be carried out ~ ;~
under cooling or at the reflux -temperature o~ the solvent used. The reaction easily proceeds by mere cx~osure of the reaction solution to li~ht, but sol~e~
times it is promoted remarkably by passin~ air or .. . .
oxygen gas into the solution. ~ `
~he quinazolinone derivatives of the formula ~
20 ~I~ obtained by the method of the present invention ` `
, . ~ .
are very use~ul as an anti-inflammatory agent, anti- ~`
viral agent, uricosuric agent and intermediates for ~ ;
other use~ul anti-inflammatory a~ents.
, According to the process o~ the present invention, thç following quinazoline derivat1ves, for example, can be obtained.
4-Phenyl-2(1H)-quinazolinone, m.p. 251 - 252C ~
4-Phenyl-6-chloro-2(lH)-quinazo~inone, m.p. ; ;
> 3~0C
4-Phenyl-6-fluoro-2(1H)-quinazolinone, . .
! ~
- : ~
1~47~67 1 m.p. ~ 300C
4-Phenyl 6-methyl-2(1H)-quinazolinone, m.p.
> 290~ :
4-Phenyl-6-methoxy-2(lH~-quinazolinone, m.p. 287C
4-Phenyl-6-nitro-2(lH)-quinazolinone, m.p.
> 300C
4~Phenyl-6-trlfluoromethyl-2(1H)-quinazolinone, m.p. 299C
, 1 Methyl-4-phenyl-6,7-dimethoxy-2(1H)- ~ `
quinazolinone, m.p. 197 - 198C . .
4-(o-Chlorophenyl)-6-nltro-2(lH)-quinazolinone, m.p. > 300C
4-(o-Fluorophenyl)-6-chloro-2(~I)-quinazolinone, ~. ~
m.p. ~ 300C ~ ~::;`3.
l-Methyl-4-phenyl-2(1~)-quina301inone, m.p.
142 - 143C ~ ~
l-Methyl-4-phenyl-6-chloro-2(IE)-quinazolinone, ..
m.p. ~20 - 221C
1-Methyl-4-phenyl-6-iodo-2(1H)-quinazolinone, m.p. 247 - 2~8C
l-Methyl-4-phenyl-6-methoxy-2(lH)-quinazolinone, m.p. 166C :
l-Methyl-4-phenyl-6-nitro-2(lH)-quinazolinone, m.p. 259 - 264C :
.
1,6-Dimethyl-4-phenyl-2(IH3-quinazolinone, ~ ~ :
o .p. 150 C : .
l-Ethyl-4-phenyl.-6-nitro-2(1H)-quinazolinone, m.p. 176 - 178C .
1-Ethyl-4-(o-tolyl)-G-chloro-2(iII)-quin~æolinone, r~ , ' ' . - ~. .... .
~ :
~1479~7 1 m.p. 138 - 139C
l-Isopropyl-~-phenyl-7-methyl-2(1H)~quinazolinone, m.p. 140C
l-Isopropyl-4-phenyl-7~methoxy-2(lH) quinazolinone, m.p. 1~7 - 1~8C
l-Isopropyl-4-phenyl-6-nitro-2(1H)-quinaæolinone, m.p. 194 - 195C
l-Isobutyl-4-phenyl-6-chloro-2(lH)-quinazolinone, m.p. 138 - 1~9C `
1-(2,2,2-Trifluoroethyl)-4-phenyl-6-chloro- ~
1(~47~a~7 .
1 ~ ~his inven~ion relates to a novel process for preparing quinazoline derivatives.
More particularly, this.invention rela-tes to a novel process for preparing quinazo]ine derivatives o~ the formula, R2 ~ R~ -' `'~
wherein Rl, R2 and R3 are independently a hydrogen atom, a halogen atom, a tri~luoromethyl group, a nitro group, a lower alkylsul~onyl group, a Iower alkyl -- group, a lower alkoxy group or a lower alkylthio ~ :
15 group; and R4 is a hydrogen atom, a lower alkyl group, :.:
.
an~aralkyl group, a lower alkanoyloxyalkyl groupj a lower alkoxyalkyl group, a polyhaloalkyl group, a . cycloalkyl group, a cycloalkylalkyl group, a tetra- ~ ~
hydrofurfuryl group, a tetrahydropyranylmethyl group, ~:
a pyridylmethyl group, a furylmethyl group or a thien~
methyl group.
In the compounds o~ the above ~ormula the term "halogen" includes all.halogen atoms, i.
fluorine~ chlorine, bromine and iodine, the term 25 "alkyl" meanS both straight and branched chain aliphatic ..
hydrocarbon radicals, and lower alkyl i5, ~or example, ;~
Cl_4~alkyl ~7hich includes such groups as methyl, ethyl, ~ . .
. .
n-propyl, isopropyl, n-butyl, isobutyl and tertiary-butyl; the term "lower alkoxy" is 9 for example, C~
~0 alkoxy which includes such ~roups as methoxy, ethoxy, ~. ;
.'.
1~7967 1 n-propoxy, isopropoxy, n-butoxy and tertiary-butoxy;
the term "aralkyl" is, for example, benæyl, phenethyl, phenylpropyl, chlorobenzyl or fluorobenzyl group; the -- term "lower alkylsulfonyl~ i3, f~r example, Cl_4 alkyl-5 sulfonyl which includes such groups as methylsulfonyl, : :~
ethylsulfonyl, propylsulfonyl, etc.; the term "iower alkanoyloxyalkyl" is, for example, (C2_3 alkanoyloxy)-Cl_4 alkyl in which the C2_3 alkànoyloxy moiety in-cludes such groups as acetoxy and propionyloxy, and 10 the Cl_4 alkyl moiety is as defined above; the term ;
"lower alkoxyalkyl" is, ~or example, (Cl_~ alkoxy)-al_4 alkyl in which both moieties are as de~ined - above; the term "polyhaloalkyl" is, for example, a trichloromethyl, trifluoromethyl, trichloroethyl, :
trifluoroethyl or pentafluoropropyl group; the term "cycloalkyl" i~, for examnle, C~ 6 cycloalkyl which includes such groups as cyclopropylj cyclobutyl, cyclo-pentyl, cyclohexyl, methylcyclopropyl, dimethylcyclo- .
propyl, etc.; the term "cycloalkylalkyl" is, for 20 example, (C3_6 cycloalkyl)-Cl_~ alkyl in which both . .
moieties are as defined above; and the term "alkyl-thio" is, ~or example, Cl_4 alkylthio which includes ~uch ~roups as methylthio, ethylthio, propylthio and :~
butylthio. ~: :
~here are some well-known methods for pre- ~ .
paring the quinazoline derivatives represented by the formula [I), and one of the most common methods among them is disclosed in Japanese Patent Publication No. ;~
48396/1972 in ~hich the quinazoline derivatives ~
~0 are obtained by reactin~ a dihydroquinazolinone derivative ~47967 1 of the formula [II~, Rl ~ NH ; (II) 5R2 ~ R3 .
wherein Rl, ~2, R3 and R4 are as defined above, with an oxidizing agent such as potassiwn permangana~e.
The above-mentioned method is, however, relatively troublesome in the operation after the reaction and further includes treatment of the oxidiz-ing agent as waste matter.
, The inventors have studled to overcome the disadvantages of those well-known methods, and found ;~
.
15 ~ that the dihydroquinazolinone derivatives of ~ormula l;
[I~ can be c~nv~rt,e~ t~ the ~uina~ol~none derivàtives of formula [I3 in a high yield by the oxidation reaotion which is caused when the dihydroqulnazolinone deriva~
tives are irradiated with light. In this method, oxidizing agents such as potassium permanganate are not necessary and operation after the reactian is very easy.
Thus, an object of the present inventio~i is to provide quina201ine derivatives o~ the formula tI), which have excellent pharmacological properties.
.
Anothèr object of the present invention;is to provide a novel process ~or producing such useful qui.nazoline ` derivatives. Other objects and~merits of the present invention`will be apparent from the following descrip~
tion.
', ' ' ' .; '''' - 3 ~
'~,. .
~ 7967 .
1 The method of the present invention is carried out by exposin~ the dihydroquinazolinone ~erivatives of the formula (II) to light.
As a light source, sun~i~ht, low-pressure and high-pressure mercury lamps may be used.
The present reaction can advanta~eously be ~-~
carried out in the presence of a solvent. The solvent includes alcohols such as methanol, ethanol an~ iso-propanol, aromatic hydrocarbons such as benzene, ~ ~
10 toluene and xylene, chloroform, acetone, dioxane, ~ ~ ' tetrahydrofuran, dimethylsulfoxide or mixtures there- ~; ;
of. ~he reaction is generally carried out at room temperature, but if necessary it may be carried out ~ ;~
under cooling or at the reflux -temperature o~ the solvent used. The reaction easily proceeds by mere cx~osure of the reaction solution to li~ht, but sol~e~
times it is promoted remarkably by passin~ air or .. . .
oxygen gas into the solution. ~ `
~he quinazolinone derivatives of the formula ~
20 ~I~ obtained by the method of the present invention ` `
, . ~ .
are very use~ul as an anti-inflammatory agent, anti- ~`
viral agent, uricosuric agent and intermediates for ~ ;
other use~ul anti-inflammatory a~ents.
, According to the process o~ the present invention, thç following quinazoline derivat1ves, for example, can be obtained.
4-Phenyl-2(1H)-quinazolinone, m.p. 251 - 252C ~
4-Phenyl-6-chloro-2(lH)-quinazo~inone, m.p. ; ;
> 3~0C
4-Phenyl-6-fluoro-2(1H)-quinazolinone, . .
! ~
- : ~
1~47~67 1 m.p. ~ 300C
4-Phenyl 6-methyl-2(1H)-quinazolinone, m.p.
> 290~ :
4-Phenyl-6-methoxy-2(lH~-quinazolinone, m.p. 287C
4-Phenyl-6-nitro-2(lH)-quinazolinone, m.p.
> 300C
4~Phenyl-6-trlfluoromethyl-2(1H)-quinazolinone, m.p. 299C
, 1 Methyl-4-phenyl-6,7-dimethoxy-2(1H)- ~ `
quinazolinone, m.p. 197 - 198C . .
4-(o-Chlorophenyl)-6-nltro-2(lH)-quinazolinone, m.p. > 300C
4-(o-Fluorophenyl)-6-chloro-2(~I)-quinazolinone, ~. ~
m.p. ~ 300C ~ ~::;`3.
l-Methyl-4-phenyl-2(1~)-quina301inone, m.p.
142 - 143C ~ ~
l-Methyl-4-phenyl-6-chloro-2(IE)-quinazolinone, ..
m.p. ~20 - 221C
1-Methyl-4-phenyl-6-iodo-2(1H)-quinazolinone, m.p. 247 - 2~8C
l-Methyl-4-phenyl-6-methoxy-2(lH)-quinazolinone, m.p. 166C :
l-Methyl-4-phenyl-6-nitro-2(lH)-quinazolinone, m.p. 259 - 264C :
.
1,6-Dimethyl-4-phenyl-2(IH3-quinazolinone, ~ ~ :
o .p. 150 C : .
l-Ethyl-4-phenyl.-6-nitro-2(1H)-quinazolinone, m.p. 176 - 178C .
1-Ethyl-4-(o-tolyl)-G-chloro-2(iII)-quin~æolinone, r~ , ' ' . - ~. .... .
~ :
~1479~7 1 m.p. 138 - 139C
l-Isopropyl-~-phenyl-7-methyl-2(1H)~quinazolinone, m.p. 140C
l-Isopropyl-4-phenyl-7~methoxy-2(lH) quinazolinone, m.p. 1~7 - 1~8C
l-Isopropyl-4-phenyl-6-nitro-2(1H)-quinaæolinone, m.p. 194 - 195C
l-Isobutyl-4-phenyl-6-chloro-2(lH)-quinazolinone, m.p. 138 - 1~9C `
1-(2,2,2-Trifluoroethyl)-4-phenyl-6-chloro- ~
2(1H)-quinazolinone, m.p. 185 - 186C ~ "' ~ 1-(2,2,3,3,3-Pentafluoropropyl)-4-phenyl-6- ~"
;~ methyl-2tlH)-quinazolinone, m.p. 175.5 - 176.5C
~ l-Benzyl-4-phenyl-6-nitro-2(1H)-quinazolinone, ; ~ 15 m.p. 173 - 174C
l-~oetoxyethyl-~-phanyl-G-chloro-2(1H)-quinazolinone, m.p. 139 - 140C i ~
~ l-Acetoxyethyl-4-phenyl-6-nitro-2(1H)- ; `~`
;~ quinazolinone, m.p. 158 - 159C ` ;~
1-(2-Ethoxyethyl)-4-phenyl-6-nitro-2(~I)-quinazolinone, m.p. 128 - 129C
l-Cyclohexyl-4-phenyl-6-nitro-2(1H)-quinazolinone, m.p. 186 - 187C
l-Cyclopropylmethyl-4-phenyl-6-chloro-2(1H)-quinazolinone, m~p. 174 - 175C
, l-Cyclopropylmethyl-4-phenyl-6-nitro-2(lH)-quinazolinone, m.p. 172 - 173C
Cyclopropylmethyl-4-phenyl-6-trifluoro-methyl-2(1~)-quinazolinone, m.p. 166 - 167C
1-Cyclopropylmethyl~4-phenyl-6-methyl-, - ~ G - -~', 1~)47967 1 sul~onyl-2 ( lH )-quinazolinone, m.p. 186 - 187C
l-Cyclopropylmethyl-4-phenyl-6-bromo 2(~I)-quinazolinone, m.p. 16~ - 164C `~
l-Cyclopropylmethyl~4-phenyl-6,~dichloro-2(~I)-quinazolinone, m.p. 158 - 159C ~`
l-Cyclopropylmethyl-4-phenyl-6~methoxy-2(1H)-quinazolinone, m.p. 115 ~ 116C
l-Cyclopropylmethyl-4-(o-fluorophenyl)-6 chloro-2tlH)-quinazolinone, m.p. 171 - 172C
1-Cyclopropylmethyl-4-phenyl-6-methylthio-2(1H)-quinazolinone, m.p. 159 - 160C r~
l-Cyclohexylethyl-4-phenyl-6-chloro-2(lH)-quinazolinone, m.p. 115 - 116C
l-Cyclopropylmethyl-4-(o-chlorophenyl)-6-nitro-2(1H)-quinazolinone, m.p. 165 - 166C
l-Cyolop~nty:Lmethyl-4-phenyl-6-nitro-2(1H)- ,:
quinazolinone, m.p. 200 - 201C
l-Cyclohexylmethyl-4-phenyl-6-nitro-2(1H)-quinazolinone, m.p. 201 - 202C
1-Tetrahydro~ur~uryl-4-phenyl-6-nitro-2(1H)-quinazolinone, m.p. lq9 - 150C
~ 2-Tetrahydropyràr~ylmethyl)-4-phenyl-6-nitro-2~I)-quinazolinone, m.p. 185 - 186C
1-(2-Pyridylmcth~1)-4-phenyl-6-nitro-2(1H)-quinazolinone, m.p. 175 - 176C ~ ;
1-(2-Furylmethyl)-4-phenyl-6-nitro-2(1H~
quinaæolinon~, m.p. 190 - 190.5C ~ ~
1-(2-Thienylmethyl)-4-phenyl-6-nitro-2(~I)- ~ ~;
quinazolinone, m.p. 219 - 220C
The lnvent.on is lllustrated more particularly .
1l~ 47 9 67 !~1 by way of the followin~ examples but, as will bc more apparent, is not limited to the details thereof.
Example 1 In 10 ml of dimethylsulfoxide was dissolved 1.0 g of 1-cyclopropylmethyl-4-phenyl-6-chloro-~,4-dihydro-2(1H)-quinazolinone and the resuIting solution -~`
was stirred for 50 hours while exposing the reaction solution to the light of a low-pressure mercury lamp used as a light source. After the reaction solution was allowed -to stand, precipitated crystals were ;
filtered, washed with isopropyl alcohol and dried to give 0.58 g of 1-cyclopropylmethyl-4-phenyl-6-chloro- ~;
2(1~)-quinazolinone, m.p. 171 - 174C.
The filtrate was diluted w1th 30 ml of water and extracted with chloroform. The extract was dried ;
over anhydrous sodium slllfate and evaporated under ~ ;
reduced pressure. The residue obtained was recry~tallized from isopropyl alcohol -to obtain 0.29 g of a second crop of crystals.
, Example 2 ~ `
In 20 ml of acetone was dissolved 0.5 g of l-cyclopropylmethyl-4-phenyl-6-chloro-3,4-dihydro-2(1H)-quinaæolinone and the resulting solution was exposed to the light of a low-pressure mercury lamp used as a light source for 57 hours. ~he reaction solution was concentrated under reduced pressure and the residue obtained was recrystallized from ~ ml of isopropyl alcohol to obtain l-cyclopropylmethyl-' ~
. ,. . - : ~ ~
~ -: , - . . . . .
1~7967 - , ' . ,': ::
1 4-phenyl-6-chloro-2(1II)-quin~zolinone, m.p. 170 -172C. -Exsmple 3 ` ~ . r `;
In 60 ml of acetone was dissolv~d 1.0 g o~
l-cyclopropylmethyl-4-phenyl-6-chloro-3,4-dihydro-2(1H)-quinazolinone and the resulting solution was exposed to the light of a low-pressure mercury lamp ;
used as a light source for 28 hours while passing air `
through the reaction solution with stirring. After removing the solvent under reduced pressure from the reaction solution, the residue obtained was recrystal-lized from 4 ml o~ isopropyl alcohoI to obtain 0.68 g of l-cyclopropylmethyl-4-phenyl-6-chloro-2(1M)- ~.
quinazolinone, m.p. 173 - 176C.
.... .... .
Example 4 The reaction solution obtained by the same procedure as Example 1 was exposed to sunlight for 50 hours in place of the light of a low-pressure meroury lamp. Operation a~ter the reaction was carried out according to Example 1 to obtain l-cyclopropylmethyl- "
4-phenyl-6-chloro-2(1H)-quinazolinone, m.p. 171 173C.
Example 5 ;~
The prooess of Exampls 1 was repssted but l-cyclopropylmethyl-4-phenyl-6-methoxy-3,4-dihydro- .
2(1H)-quina~olinone was used in place of l~cyclo-prop~vImethyl-4~phenyl-6-chloro-3,4~dihydro-2(1H)- ~ ;~
:
~ . . .
s 9 `- s :
.~ ~
~47~;7 : ~
:
1 quinazoli~lone. Thus, l-cyclopropylmethyl-4-phenyl-6-methoxy-2-(IH)-quinazolinone9 m.p. 115 - 116C, was obtained. ~ .
.
:.i ' `;` ~ ~'~'',.' ` ~ ~.','~`
.~
. . :
: ~' `'' ` .` :
.. . . ` :' .
- ~ ~
,, , . ,., - 10 _ , :
:"' .
;~ methyl-2tlH)-quinazolinone, m.p. 175.5 - 176.5C
~ l-Benzyl-4-phenyl-6-nitro-2(1H)-quinazolinone, ; ~ 15 m.p. 173 - 174C
l-~oetoxyethyl-~-phanyl-G-chloro-2(1H)-quinazolinone, m.p. 139 - 140C i ~
~ l-Acetoxyethyl-4-phenyl-6-nitro-2(1H)- ; `~`
;~ quinazolinone, m.p. 158 - 159C ` ;~
1-(2-Ethoxyethyl)-4-phenyl-6-nitro-2(~I)-quinazolinone, m.p. 128 - 129C
l-Cyclohexyl-4-phenyl-6-nitro-2(1H)-quinazolinone, m.p. 186 - 187C
l-Cyclopropylmethyl-4-phenyl-6-chloro-2(1H)-quinazolinone, m~p. 174 - 175C
, l-Cyclopropylmethyl-4-phenyl-6-nitro-2(lH)-quinazolinone, m.p. 172 - 173C
Cyclopropylmethyl-4-phenyl-6-trifluoro-methyl-2(1~)-quinazolinone, m.p. 166 - 167C
1-Cyclopropylmethyl~4-phenyl-6-methyl-, - ~ G - -~', 1~)47967 1 sul~onyl-2 ( lH )-quinazolinone, m.p. 186 - 187C
l-Cyclopropylmethyl-4-phenyl-6-bromo 2(~I)-quinazolinone, m.p. 16~ - 164C `~
l-Cyclopropylmethyl~4-phenyl-6,~dichloro-2(~I)-quinazolinone, m.p. 158 - 159C ~`
l-Cyclopropylmethyl-4-phenyl-6~methoxy-2(1H)-quinazolinone, m.p. 115 ~ 116C
l-Cyclopropylmethyl-4-(o-fluorophenyl)-6 chloro-2tlH)-quinazolinone, m.p. 171 - 172C
1-Cyclopropylmethyl-4-phenyl-6-methylthio-2(1H)-quinazolinone, m.p. 159 - 160C r~
l-Cyclohexylethyl-4-phenyl-6-chloro-2(lH)-quinazolinone, m.p. 115 - 116C
l-Cyclopropylmethyl-4-(o-chlorophenyl)-6-nitro-2(1H)-quinazolinone, m.p. 165 - 166C
l-Cyolop~nty:Lmethyl-4-phenyl-6-nitro-2(1H)- ,:
quinazolinone, m.p. 200 - 201C
l-Cyclohexylmethyl-4-phenyl-6-nitro-2(1H)-quinazolinone, m.p. 201 - 202C
1-Tetrahydro~ur~uryl-4-phenyl-6-nitro-2(1H)-quinazolinone, m.p. lq9 - 150C
~ 2-Tetrahydropyràr~ylmethyl)-4-phenyl-6-nitro-2~I)-quinazolinone, m.p. 185 - 186C
1-(2-Pyridylmcth~1)-4-phenyl-6-nitro-2(1H)-quinazolinone, m.p. 175 - 176C ~ ;
1-(2-Furylmethyl)-4-phenyl-6-nitro-2(1H~
quinaæolinon~, m.p. 190 - 190.5C ~ ~
1-(2-Thienylmethyl)-4-phenyl-6-nitro-2(~I)- ~ ~;
quinazolinone, m.p. 219 - 220C
The lnvent.on is lllustrated more particularly .
1l~ 47 9 67 !~1 by way of the followin~ examples but, as will bc more apparent, is not limited to the details thereof.
Example 1 In 10 ml of dimethylsulfoxide was dissolved 1.0 g of 1-cyclopropylmethyl-4-phenyl-6-chloro-~,4-dihydro-2(1H)-quinazolinone and the resuIting solution -~`
was stirred for 50 hours while exposing the reaction solution to the light of a low-pressure mercury lamp used as a light source. After the reaction solution was allowed -to stand, precipitated crystals were ;
filtered, washed with isopropyl alcohol and dried to give 0.58 g of 1-cyclopropylmethyl-4-phenyl-6-chloro- ~;
2(1~)-quinazolinone, m.p. 171 - 174C.
The filtrate was diluted w1th 30 ml of water and extracted with chloroform. The extract was dried ;
over anhydrous sodium slllfate and evaporated under ~ ;
reduced pressure. The residue obtained was recry~tallized from isopropyl alcohol -to obtain 0.29 g of a second crop of crystals.
, Example 2 ~ `
In 20 ml of acetone was dissolved 0.5 g of l-cyclopropylmethyl-4-phenyl-6-chloro-3,4-dihydro-2(1H)-quinaæolinone and the resulting solution was exposed to the light of a low-pressure mercury lamp used as a light source for 57 hours. ~he reaction solution was concentrated under reduced pressure and the residue obtained was recrystallized from ~ ml of isopropyl alcohol to obtain l-cyclopropylmethyl-' ~
. ,. . - : ~ ~
~ -: , - . . . . .
1~7967 - , ' . ,': ::
1 4-phenyl-6-chloro-2(1II)-quin~zolinone, m.p. 170 -172C. -Exsmple 3 ` ~ . r `;
In 60 ml of acetone was dissolv~d 1.0 g o~
l-cyclopropylmethyl-4-phenyl-6-chloro-3,4-dihydro-2(1H)-quinazolinone and the resulting solution was exposed to the light of a low-pressure mercury lamp ;
used as a light source for 28 hours while passing air `
through the reaction solution with stirring. After removing the solvent under reduced pressure from the reaction solution, the residue obtained was recrystal-lized from 4 ml o~ isopropyl alcohoI to obtain 0.68 g of l-cyclopropylmethyl-4-phenyl-6-chloro-2(1M)- ~.
quinazolinone, m.p. 173 - 176C.
.... .... .
Example 4 The reaction solution obtained by the same procedure as Example 1 was exposed to sunlight for 50 hours in place of the light of a low-pressure meroury lamp. Operation a~ter the reaction was carried out according to Example 1 to obtain l-cyclopropylmethyl- "
4-phenyl-6-chloro-2(1H)-quinazolinone, m.p. 171 173C.
Example 5 ;~
The prooess of Exampls 1 was repssted but l-cyclopropylmethyl-4-phenyl-6-methoxy-3,4-dihydro- .
2(1H)-quina~olinone was used in place of l~cyclo-prop~vImethyl-4~phenyl-6-chloro-3,4~dihydro-2(1H)- ~ ;~
:
~ . . .
s 9 `- s :
.~ ~
~47~;7 : ~
:
1 quinazoli~lone. Thus, l-cyclopropylmethyl-4-phenyl-6-methoxy-2-(IH)-quinazolinone9 m.p. 115 - 116C, was obtained. ~ .
.
:.i ' `;` ~ ~'~'',.' ` ~ ~.','~`
.~
. . :
: ~' `'' ` .` :
.. . . ` :' .
- ~ ~
,, , . ,., - 10 _ , :
:"' .
Claims (6)
EXCLUSIVE PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED
AS FOLLOWS:
1. A process for producing a quinazolinone derivative of the formula, [I]
wherein R1, R2 and R3 are independently a hydrogen atom, a halogen atom, a trifluoromethyl group, a nitro group, a lower alkylsulfonyl group, a lower alkyl group, a lower alkoxy group or a lower alkylthio group; and R4 is a hydrogen atom, a lower alkyl group, an aralkyl group, a lower alkanoyloxyalkyl group, a lower alkoxy-alkyl group, a polyhaloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, a tetrahydrofurfuryl group, a tetrahydropyranylmethyl group, a pyridylmethyl group, a furylmethyl group or a thienylmethyl group, which comprises irradiating a dihydroquinazolinone derivative of the formula, [II]
wherein R1, R2, R3 and R4 have the same meanings as defined above, with light.
wherein R1, R2 and R3 are independently a hydrogen atom, a halogen atom, a trifluoromethyl group, a nitro group, a lower alkylsulfonyl group, a lower alkyl group, a lower alkoxy group or a lower alkylthio group; and R4 is a hydrogen atom, a lower alkyl group, an aralkyl group, a lower alkanoyloxyalkyl group, a lower alkoxy-alkyl group, a polyhaloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, a tetrahydrofurfuryl group, a tetrahydropyranylmethyl group, a pyridylmethyl group, a furylmethyl group or a thienylmethyl group, which comprises irradiating a dihydroquinazolinone derivative of the formula, [II]
wherein R1, R2, R3 and R4 have the same meanings as defined above, with light.
2. A process according to Claim 19 wherein the reaction is carried out by exposing to sunlight or the light of a low-pressure or high-pressure mercury lamp.
3. A process according to Claim 1, wherein the reaction is carried out in a solvent.
4. A process according to Claim 3, wherein the solvent is selected from the group consisting of methanol, ethanol, isopropanol, benzene, toluene, xylene, chloro-form, acetone, dioxane, tetrahydrofuran, dimethylsulfoxide and a mixture thereof.
5. A process according to Claim 1, wherein the reaction is carried out at room temperature.
6. A process according to Claim 1, wherein the reaction is carried out by introducing air or oxygen gas to the reaction system.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49061684A JPS5919098B2 (en) | 1974-05-30 | 1974-05-30 | Method for producing quinazoline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1047967A true CA1047967A (en) | 1979-02-06 |
Family
ID=13178325
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA228,044A Expired CA1047967A (en) | 1974-05-30 | 1975-05-29 | Process for preparation of quinazolines |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS5919098B2 (en) |
| AT (1) | AT346335B (en) |
| CA (1) | CA1047967A (en) |
| CH (1) | CH599172A5 (en) |
| NL (1) | NL7506338A (en) |
| SE (1) | SE414403B (en) |
-
1974
- 1974-05-30 JP JP49061684A patent/JPS5919098B2/en not_active Expired
-
1975
- 1975-05-28 AT AT408875A patent/AT346335B/en not_active IP Right Cessation
- 1975-05-29 SE SE7506140A patent/SE414403B/en unknown
- 1975-05-29 CA CA228,044A patent/CA1047967A/en not_active Expired
- 1975-05-29 NL NL7506338A patent/NL7506338A/en not_active Application Discontinuation
- 1975-05-30 CH CH702675A patent/CH599172A5/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE414403B (en) | 1980-07-28 |
| SE7506140L (en) | 1975-12-01 |
| CH599172A5 (en) | 1978-05-12 |
| ATA408875A (en) | 1978-03-15 |
| NL7506338A (en) | 1975-12-02 |
| AT346335B (en) | 1978-11-10 |
| JPS50151887A (en) | 1975-12-06 |
| JPS5919098B2 (en) | 1984-05-02 |
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