Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-03-08
2002-04-23
Rotman, Alan L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C564S313000
Reexamination Certificate
active
06376678
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a production method of a hydrazine derivative having a group of the formula (II)
which is stable even in a solution state.
BACKGROUND OF THE INVENTION
A hydrazine derivative having a group of the formula (II)
(hereinafter is to be also referred to as hydrazine derivative (II)) can be generally obtained by subjecting a hydrazone derivative having a group of the formula (I)
(hereinafter to be also referred to as hydrazone derivative (I) to catalytic reduction. When the hydrazine derivative (II) obtained by a known method is preserved in a suitable organic solvent, such as isopropyl alcohol, the hydrazine derivative (II) converts to the hydrazone -drivative (I) and becomes an impurity in the next step. Thus a production method of hydrazine derivative (II), which is stable even in a solution state, has been desired.
In addition, tert-butyl3-[4-(pyridin-2-yl)benzyllcarbazate of the formula
wherein tBu is tert-butyl (hereinafter to be also referred to as a hydrazine derivative (IIb), which is among the hydrazine derivatives (II), is useful as a synthetic intermediate for compound (A) of the formula
which is an anti-HIV drug. For example, N-(tert-butoxycarbonyl)-N′-[4-(pyridin-2-yl )phenylmethylidene]hydrazine of the formula
wherein tBu is tert-butyl [hereinafter to be also referred to as hydrazone derivative (Ib)], which is among the hydrazone derivatives (I), can be treated by the method described in WO97/40029 to give the medicament of compound (A) via hydrazine derivative (IIb).
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to provide a production method of hydrazine derivative (II) which is stable even in a solution state.
Such object can be achieved by the following invention which affords a method comprising subjecting a hydrazone derivative (I) to catalytic reduction and deactivating the reduction catalyst contained in the reaction mixture thereof. According to the method of the present invention, a hydrazine derivative (II), which is free of hydrazone derivative (I) and which is stable even in a solution state, can be obtained by preserving the derivative in an organic solvents Accordingly the present invention provides (1) a production method of hydrazine derivative having a group of the formula (II)
which comprises subjecting a hydrazone derivative having a group of the formula (I)
to catalytic reduction and deactivating the reduction catalyst contained in the reaction mixture thereof; (2) the production method of (1) above, wherein the hydrazone derivative (I) is a hydrazone derivative (Ia) of the formula
wherein R is hydrogen atom, halogen atom, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, optionally substituted aryl or optionally substituted aromatic heterocyclic group, R′ is hydrogen atom, acyl, alkoxycarbonyl, alkyl -or optionally substituted phenyl and R″ is acyl, alkoxycarbonyl, alkyl or optionally substituted phenyl, and the hydrazine derivative (II) is a hydrazine derivative (IIa) of the formula
wherein R, R′ and R″ are as defined above; (3) the production method of (1) above, wherein the step for deactivating the reduction catalyst comprises the use of a catalytic poison and/or an adsorbent, (4) the production method of (3) above, wherein the catalytic poison is a sulfur compound; (5) the production method of (4) above, wherein the sulfur compound is sodium hydrosulfite, (6) the production method of (3) above, wherein the adsorbent is an active charcoal, (7) the production method of (1) above; which further comprises, after deactivation of the reduction catalyst, recrystallizing in a solvent containing a saturated hydrocarbon solvent and (8) the production method of any of (1)-(7) above, wherein the hydrazine derivative (II) is tert-butyl3-[4-(pyridin-2-yl)benzyl]carbazate.
DETAILED DESCRIPTION OF THE INVENTION
The terms and substituents used in the present specification are defined in the following.
A typical catalytic poison is a substance that strikingly reduces or eliminates the activity of a catalyst used in a catalytic reaction. As used in this specification, the catalytic poison eliminates the catalytic activity.
As used in this specification, by halogen atom is meant, unless particularly specified, a fluorine atom, chlorine atom, bromine atom or iodine atom.
As used in this specification, by alkyl is meant, unless particularly specified, a linear or branched chain alkoxy having 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl.
As used in this specification, by alkoxy is meant, unless particularly specified, linear or branched chain alkyl having 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy and tert-butoxy.
As used in this specification, by alkoxycarbonyl is meant, unless particularly specified, alkoxycarbonyl having 2 to 5 carbon atoms wherein the alkoxy moiety is linear or branched chain alkoxy. Examples thereof include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl,. butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl and tert-butoxycarbonyl.
The halogen atom at R is a fluorine atom, chlorine atom, bromine atom or iodine atom, preferably a fluorine atom, chlorine atom or bromine atom.
The alkyl having 1 to 4 carbon atoms at R is linear or branched chain alkyl having 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, preferably tert-butyl.
The alkoxy having 1 to 4 carbon atoms at R is linear or branched chain alkoxy having 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy and tert-butoxy, preferably methoxy and ethoxy.
The optionally substituted aryl at R is aryl optionally having the following 1 to 3, preferably 1 or 2, substituents, without particular limitation on the substitution site. As aryl, exemplified are phenyl and naphthyl. The substituent may be any as long as it is not reduced by the catalytic reduction used in the present inventions. Examples thereof include alkyl, alkoxy, halogen atom, carboxy, alkoxycarbonyl and cyano. The optionally substituted aryl is exemplified by phenyl, 2-, 3- or 4-tolyl, 2-, 3- or 4-methoxyphenyl, 2-, 3- or 4-fluorophenyl, 2-, 3- or 4-chlorophenyl, 2-, 3- or 4-carboxyphenyl and 2-, 3- or 4-cyanophenyl, preferably phenyl The optionally substituted aromatic heterocyclic group at R is an aromatic heterocyclic group optionally having the following 1 to 3, preferably 1 or 2, substituents. The aromatic heterocyclic group is that having at least one hetero atom selected from the group of N, O, and S, such as furyl, oxazolyl, imidazolyl, pyridyl and pyrimidinyl. The substituent may be any as long as it is not reduced by the catalytic reduction used in the present invention, without particular limitation on the substitution site. Examples thereof include alkyl, alkoxy, halogen atom, carboxy, alkoxycarbonyl and cyano. The optionally substituted aromatic heterocyclic group may be 2-, 3-or 4-pyridyl, preferably 2-pyridyl.
The acyl at R′ and R″ may be, for example, formyl, acetyl, propionyl, butyryl or benzoyl, preferably acetyl or benzoyl.
The alkoxycarbonyl at R′ and ″ is that having 2 to 5 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl and tert-butoxycarbonyl, preferably tert-butoxycarbonyl.
The alkyl at R′ and R″ is linear or branched chain alkyl having 1 to 8, preferably 1 to 4, carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl and octyl, preferably methyl, ethyl and propyl.
The optionally substituted phenyl at R′ and R″ is phenyl optionally having the following 1 to 3, preferably 1 or 2, substituents, without particular limitation on the substitut
Itaya Nobushige
Matsui Kozo
Shintaku Tetsuya
Sugi Kiyoshi
Leydig , Voit & Mayer, Ltd.
Robinson Binta
Rotman Alan L.
Sumika Fine Chemicals Co., Ltd.
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