Process for the preparation of imidazole derivatives

Details Process for the preparation of imidazole derivatives Process for the preparation of imidazole derivatives

2002-04-12

2004-03-30

McKane, Joseph K. (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C548S341500, C546S274700

Reexamination Certificate

active

06713632

ABSTRACT:

TECHNICAL FIELD
The present invention relates to a production method of a naphthalene derivative showing a pharmaceutical effect such as a steroid C
17,20
lyase inhibitory action and the like, and an intermediate therefor.
BACKGROUND ART
As a synthetic method of a compound wherein an aromatic compound is substituted by an alkanoyl group, for example, the following reactions are known.
(1) JP-A-7-285945 discloses a reaction shown by
wherein R
1
and R
2
are each a hydrogen atom, a halogen atom, an alkyl group and the like, and R
3
is a hydrogen atom, an alkyl group, an aryl group and the like,
(2) Tetrahedron 49(7), 1431 (1993) discloses a reaction shown by
and
(3) J. Org. Chem. 59(17), 4844 (1994) discloses a reaction shown by
DISCLOSURE OF THE INVENTION
The present inventors have conducted intensive studies of a production method of the compound of the following formula (V) having a superior steroid C
17,20
lyase inhibitory action and the like and an intermediate therefor, and found that the synthesis of a compound of the following formula (V) from a compound of the following formula (VI) via a compound of the following formula (I) and a compound of the following formula (III) unexpectedly leads to an industrially advantageous production of a compound of the following formula (V), by which the compound can be obtained in a high yield with a less number of steps without using a heavy metal compound.
Accordingly, the present invention relates to:
(1) a method for producing a compound of the formula:
wherein R is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group and ring A is an imidazole ring which may-be further substituted, or a salt thereof, which method comprises reacting a compound of the formula:
wherein ring,A is as defined above, or a salt thereof, and a compound of the formula:
R—M
1
  (II)
wherein M
1
is an alkali metal atom or a group of the formula: —Mg—Y
1
(Y
1
is a halogen atom) and R is as defined above, or a salt thereof, and bringing the resulting product into contact with an acid;
(2) a method for producing a compound of the formula:
wherein R
1
, R
2
, R
3
, R
4
, R5, R
6
and R
7
are each independently a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted hydroxyl group, an optionally substituted thiol group, an optionally substituted amino group, an acyl group or a halogen atom and other symbols are as defined above, or a salt thereof, which method comprises reacting a compound of the formula (III) or a salt thereof and a compound of the formula:
wherein M
2
is an alkali metal atom or a group of the formula: —Mg—y
2
(Y
2
is a halogen atom) and other symbols are as defined above, or a salt thereof;
(3) a method for producing a compound of the formula (V) or a salt thereof, which method comprises reacting compound of the formula (I) or a salt thereof and a compound of the formula (II) or a salt thereof, bringing the resulting product into contact with an acid to give a compound of the formula (III) or a salt thereof, and then reacting this compound and a compound of the formula (IV) or a salt thereof;
(4) a method for producing a compound of the formula (V) or a salt thereof, which method comprises reacting a compound of the formula:
wherein ring A is as defined above, or a salt thereof, and hydroxylamine or a salt thereof, subjecting the resulting product to dehydration to give a compound of the formula (I) or a salt thereof, reacting this compound and a compound of the formula (II) or a salt thereof, bringing the resulting product into contact with an acid to give a compound of the formula (III) or a salt thereof, and reacting this compound and a compound of the formula (Iv) or a salt thereof;
(5) the production method described in the above-mentioned (1), (2), (3) or (4), wherein the ring A of the compounds of the formulas (I), (III), (V) and (VI) is an imidazole ring wherein the 1- or 3-position is optionally protected;
(6) the production method described in the above-mentioned (1), (2), (3) or (4), wherein R is an optionally substituted lower alkyl group, an optionally substituted lower alkenyl group, an optionally substituted cycloalkyl group, an optionally substituted phenyl group or an optionally substituted pyridyl group;
(7) the production method described in the above-mentioned (1), (2), (3) or (4), wherein R is a lower alkenyl group, a cycloalkyl group, a phenyl group, a pyridyl group, or a lower alkyl group optionally substituted by a ha log atom;
(8) the production method described in the above-mentioned (1), (2), (3) or (4), wherein R is a C
1-6
alkyl group;
(9) the production method described in the above-mentioned (1), (2), (3) or (4), wherein R is an isopropyl group;
(10) the production method described in the above-mentioned (2), (3) or (4), wherein M is sodium, potassium or a group of the formula: —Mg—Y
2
(y
2
is a halogen atom);
(11) the production method described in the above-mentioned (1), (3) or (4), wherein the reaction product of a compound of the formula (I) or a salt thereof and a compound of the formula (II) or a salt thereof is brought into contact with a sulfuric acid;
(12) the production method described in the above-mentioned (1), (3) or (4), wherein not less than 3 equivalents of the compound of the formula (II) or a salt thereof is used per one equivalent of the compound of the formula (I) or a salt thereof;
(13) the production method described in the above-mentioned (1), (3) or (4), wherein the compound of the formula (I) or a salt thereof and the compound of the formula (II) or a salt thereof are reacted in tetrahydrofuran;
(14) the production method described in the above-mentioned (1), (3) or (4) wherein the compound of the formula (I) or a salt thereof and the compound of the formula (II) or a salt thereof are reacted in not less than 50 equivalents of a solvent relative to one equivalent of the compound of the formula (I) or a salt thereof;
(15) a compound of the formula:
wherein R′ is an optionally substituted alkyl group having 3 or more carbon atoms, or a salt thereof;
(16) the compound of the above-mentioned (15), wherein R′ is an optionally substituted branched alkyl group having 3 or more carbon atoms;
(17) 1-(1H-imidazol-4-yl)-2-methyl-1-propanone or a salt thereof; and the like.
In the above-mentioned formulas, the alkali metal atom shown by M
1
and M
2
includes, for example, sodium atom, potassium atom, lithium atom and the like.
The halogen atom shown by Y
1
and y
2
includes, for example, fluorine atom, chlorine atom, bromine atom, iodine atom and the like.
In the above-mentioned formulas (I), (III), (IIIa), (V) and (VI), the ring A is an imidazole ring which may be further substituted, and the formula:
and may have additional substituent(s) besides the substituent(s) already present on the ring.
As the optional and additional substituent(s), 1 to 3 substituent(s) may be present at substitutable position(s) of the nitrogen atom and/or the carbon atom forming the imidazole ring. The group that substitutes the nitrogen atom includes those known as amino-protecting groups that do not affect this reaction, such as C
7-20
aralkyl (e.g., benzyl, trityl, phenylethyl, benzhydryl etc.) and the like. These protecting groups may have additional substituent(s) at substitutable optional position(s). Such substituent includes halogen atom (e.g., fluorine, chlorine, bromine, iodine e t ), nitro group, methoxy group and the like, wherein the number of the substituent(s) is generally 1 to 3. These protecting groups can be removed easily by hydrolysis, oxidation, reduction and a typical removing method. The group that substitutes carbon atom of the ring A includes, for example, an optionally substituted lower alkyl group, an optionally substituted lower alkoxy group, an optionally substituted alkylsulfonyl group, an optionally substituted carbamoyl group, an optionally substituted sulfamoyl group and the like. The optionally substituted lower alkyl includes, for example, unsubstituted C
1-4
alkyl gr

Affiliated with

Also associated with

Rating

Process for the preparation of imidazole derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for the preparation of imidazole derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of imidazole derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3251932