Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-12-04
2003-11-18
Davis, Zinna Northington (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C546S315000
Reexamination Certificate
active
06649768
ABSTRACT:
The present invention relates to a production method of an imidazole compound or a salt thereof, which is a synthetic intermediate for a compound useful as pharmaceutical agents and agricultural chemicals, and a novel intermediate useful for the production of the imidazole compound.
BACKGROUND ART
Imidazole compound is a synthetic intermediate for a compound useful as pharmaceutical agents and agricultural chemicals. For example, 3-(4-imidazolyl)pyridine is useful as a synthetic intermediate for telithromycin useful as antibiotics.
There have been developed various synthetic methods of imidazole compounds including 3-(4-imidazolyl)pyridine useful as such synthetic intermediate. In WO00/02875, for example, 3-(4-imidazolyl)pyridine is produced from 3-acetylpyridine as a starting material through oximation, tosylation, azirine formation, ring opening in acidic alcohol and ring closure to imidazole in formamide. However, such production methods are complicated and unsuitable as industrial production methods. Therefore, the development of a method for conveniently producing 3-(4-imidazolyl)pyridine and a salt thereof, which is suitable for industrial scale production, is desired.
It is therefore an object of the present invention to provide 1) a method capable of conveniently producing 3-(4-imidazolyl)pyridine and a salt thereof, which is suitable for industrial scale production, and 2) a novel intermediate and a salt thereof for an imidazole compound.
DISCLOSURE OF THE INVENTION
As a result of the intensive studies done by the present inventors in an attempt to achieve the above-mentioned object, they have found that an imidazole compound of the following formula (1) can be conveniently produced via the following step 2 and step 3, and that this method is suitable for industrial scale production, which resulted in the completion of the present invention.
The present inventors have further found a method for producing a glyoxal compound of the following formula (2) (hereinafter to be also referred to as glyoxal compound (2)), which comprises halogenating a carbonyl compound of the following formula (5) (hereinafter to be also referred to as carbonyl compound (5)) to give a halogen compound of the following formula (6) (hereinafter to be also referred to as halogen compound (6)) and converting a —CHnXm group of the halogen compound (6) to an aldehyde group, and completed the present invention.
Accordingly, the present invention relates to the following (1) to (5).
(1) A production method of an imidazole compound of the formula (1)
wherein
R
1
is an aryl group optionally having substituent(s) or a heterocyclic residue optionally having substituent(s); and
R
2
is a hydrogen atom, an alkyl group optionally having substituent(s), an unsaturated alkyl group optionally having substituent(s), a cycloalkyl group optionally having substituent(s), an aralkyl group optionally having substituent(a), an arylalkenyl group optionally having substituent(s), an aryl-cyclic hydrocarbon group optionally having substituent(s), an aryl group optionally having substituent(s) or a heterocyclic residue optionally having substituent(s) (hereinafter to be also referred to as imidazole compound (1)),
or a salt thereof, which comprises
step 2: a step for converting, in dimethyl sulfoxide, a halogen compound of the formula (6)
wherein R
1
is as defined above, X is a chlorine atom or a bromine atom, m and n are each an integer of 1 or 2, and m+n is 3,
or a salt thereof, to a glyoxal compound of the formula (2)
wherein R
1
is as defined above,
or a salt thereof, and
step 3: a step for reacting the glyoxal compound (2) or a salt thereof obtained in step 2 with ammonia and an aldehyde compound of the formula (3)
wherein R
2
is as defined above (hereinafter to be also referred to as aldehyde compound (3)) or a salt thereof.
(2) The production method of the above-mentioned (1), which further comprises step 1: a step for obtaining a halogen compound (6) or a salt thereof by chlorination or bromination of a carbonyl compound of the formula (5)
wherein R
1
is an aryl group optionally having substituent(s) or a heterocyclic residue optionally having substituent(s), and R
3
is a hydrogen atom or an alkoxycarbonyl group,
or a salt thereof.
(3) The production method of the above-mentioned (1) or (2), wherein, in step 2, a base is added after confirmation of the start of the conversion of the halogen compound (6) or a salt thereof to the glyoxal compound (2) or a salt thereof.
(4) The production method of any of the above-mentioned (1) to (3), wherein, R
1
is a 3-pyridyl group and R
2
is a hydrogen atom.
(5) (3-Pyridyl)glyoxal, a solvate thereof or a salt thereof.
EMBODIMENT OF THE INVENTION
The definition of each symbol is given in the following.
The alkyl group in the present invention is preferably a linear or branched alkyl group having 1 to 24 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, undecyl and the like.
The unsaturated alkyl group in the present invention is preferably a linear or branched unsaturated alkyl group having 2 to 24 carbon atoms, such as alkenyl (e.g., vinyl, 1-propenyl, 2-propenyl, isopropenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, dodecenyl, undecenyl and the like); and alkynyl (e.g., ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, dodecynyl, undecynyl and the like).
The cycloalkyl group in the present invention is preferably a saturated or unsaturated cycloalkyl having 3 to 6 carbon atoms, such as cyclopropyl, cyclohexyl and the like.
The aryl group in the present invention is exemplified by phenyl, naphthyl, anthranyl and the like.
The aralkyl group in the present invention is preferably an aralkyl group having 7 to 24 carbon atoms, wherein the alkyl moiety is linear or branched. Examples thereof include benzyl, phenethyl, naphthylmethyl and the like.
The arylalkenyl group in the present invention preferably has 8 to 24 carbon atoms, wherein the aryl moiety is as defined for the above-mentioned aryl and the alkenyl moiety is linear or branched. Examples thereof include phenylethenyl, phenylpropenyl, phenylbutenyl, naphthylethenyl, naphthylpropenyl and the like.
The aryl-cyclic hydrocarbon group in the present invention preferably has 9 to 24 carbon atoms, wherein the aryl moiety is as defined for the above-mentioned aryl and the cyclic hydrocarbon moiety is saturated or unsaturated.
Examples thereof include phenylcyclopropyl, phenylcyclopentyl, phenylcyclohexyl, naphthylcyclopropyl, naphthylcyclopentyl, naphthylcyclohexyl and the like.
The heterocyclic residue in the present invention is preferably an unsaturated 5- or 6-membered ring having 1 or more hetero atoms (e.g., nitrogen atom, oxygen atom, sulfur atom and the like). Examples thereof include furyl group, thienyl group, pyridyl group, pyrimidinyl group, quinolyl group and the like.
The alkoxycarbonyl group in the present invention is preferably a linear or branched alkoxycarbonyl group having 2 to 8 carbon atoms. Examples thereof include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, heptyloxycarbonyl and the like, with preference given to methoxycarbonyl and ethoxycarbonyl.
The aryl group and heterocyclic residue for R
1
and alkyl group, unsaturated alkyl group, cycloalkyl group, aralkyl group, aryl group, arylalkenyl group, aryl-cyclic hydrocarbon group and heterocyclic residue for R
2
are optionally substituted with 1 or more substituents. Examples of the substituent include linear or branched alkyl group having 1 to 12 carbon atoms (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl and the like), unsaturated alkyl group, halogen atom (fluorine atom, chlorine atom, bromine atom, iodine atom), linear or branched alkoxy group having 1 to 12 carbon atoms (e.g.,
Itaya Nobushige
Shintaku Tetsuya
Davis Zinna Northington
Leydig , Voit & Mayer, Ltd.
Sumika Fine Chemicals Co., Ltd.
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