JP2003286245A - Method for producing ortho-aminobenzenesulfonamide compound - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing various kinds of o- aminobenzenesulfonamide compounds in good yield from an easily available raw material. <P>SOLUTION: The method for producing the o-aminobenzenesulfonamide compound represented by general formula (I) comprises the following steps (1) to (4): (1) a step for introducing a protective group to the amino group of a compound represented by general formula (II); (2) a step for halogenating the sulfo group of the compound obtained in the step (1); (3) a step for forming a sulfonamide by using the sulfonyl chloride obtained at the step (2) and a primary amine; and (4) a step for deprotecting the compound obtained at the step (3) to synthesize the compound represented by general formula (I). (In the formulas, R<SB>1</SB>is a substituted or unsubstituted alkyl group or aryl group; R<SB>2</SB>is a substituent; n is an integer of 0-4; when n is ≥2, two or more R<SB>2</SB>s are the same or different, and may form a ring by bonding to each other). <P>COPYRIGHT: (C)2004,JPO

Description

DETAILED DESCRIPTION OF THE INVENTION [0001] The present invention relates to a silver halide photograph.
Yellow couplers used in photosensitive materials-intermediates, dyes, medicines
Various useful as synthetic intermediates for drugs, agricultural chemicals, electronic materials, etc.
The present invention relates to a method for producing a sulfonamide compound. [0002] [0002] Orthoaminobenzenesulfonamidation
As a method for synthesizing the compound, alteranilic acid was converted to chlorosulfone.
Acid chloride with acid solvent, amination after removal
A method of synthesis by reacting with a compound is disclosed in US Pat. No. 1,91.
No. 1,719 (1930). However
However, this method uses chlorosulfonic acid as a solvent.
A large amount of acid in the treatment of sulfuric acid produced as a by-product in large quantities.
It is unrealistic as a method of mass production that requires Lucari
It is. On the other hand, ortho-nitrobenzene sulfo
Nitrochloride as starting material, amidation followed by nitro group
Of orthoaminobenzenesulfonamide by reduction of
A method for synthesizing a product is common, for example, Japanese Patent Laid-Open No. 6-1.
An example can be found in 92272. However,
In addition, metallic iron is used to reduce the nitro group, and its treatment
Because of this problem, there are many restrictions on mass production. As above
The production method is limited, and ortho-amino acids are suitable for production.
Strong development of simple synthesis methods for benzenesulfonamide compounds
It is desired. [0003] Accordingly, it is an object of the present invention.
Is a source that does not have the above-mentioned problems and is easily available.
From various materials, various orthoaminobenzenesulfones were obtained in good yield.
To provide a method for producing a large amount of a non-amide compound
is there. [0004] The object of the present invention is to:
Achieved by law. That is, the present invention (1) It has the following steps 1) to 4)
Preparation of a sulfonamide compound represented by the following general formula (I)
Manufacturing method. 1) Preserving the amino group of the compound represented by the following general formula (II)
It is represented by the following general formula (III) by the reaction protected with a protective group.
For synthesizing compounds 2) The sulfo group of the compound represented by the general formula (III)
Rogenated to synthesize compounds represented by the following general formula (IV)
Process 3) The compound represented by the general formula (IV) and the following general formula
The compound represented by (V) is represented by the following general formula (VI).
Of synthesizing compounds 4) Deprotecting the compound represented by the general formula (VI)
Step of synthesizing a compound represented by the general formula (I) [0005] [Chemical 2] In general formulas (I), (V) and (VI)
R₁Is a substituted or unsubstituted alkyl group or ant
Represents an alkyl group. In general formulas (I) to (IV) and (VI)
And R₂Represents a substituent. n is an integer from 0 to 4
Represent. multiple n when n is 2 or more₂Are the same
They may be different and may be joined together to form a ring.
Yes. In the general formulas (III), (IV) and (VI), A
Represents a protected amino group. In general formula (IV):
X represents a halogen atom. (2) In the step 1), the reaction is performed in the presence of a base.
It is represented by the general formula (I) described in (1)
A method for producing a sulfonamide compound. (3) In the general formulas (III), (IV) and (VI)
A is represented by the following general formula (VII), (VIII) or (IX)
(1) or (2) characterized by being a group represented
Sulfonamide compounds represented by the general formula (I)
Manufacturing method. [0007] [Chemical 3] Where Z₁And Z₂Are independently oxygen fields
Child, -N (R₁₁)-Group, or -C (R
₁₃) (R₁₂)-Represents a group represented by-. here,
R_{1 1}, R₁₂And R₁₃Are each independently a hydrogen atom,
Or a substituted or unsubstituted alkyl group or aryl group
Represent. Z₃Is the non-gold required to form a 5- to 7-membered ring
Represents a group of atomic atoms. R₁₄And R₁₅Are each independently water
An elementary atom, or a substituted or unsubstituted alkyl group,
Represents a diol group. [0009] The present invention will be described in detail below.
First, the compound of the present invention will be described. The present invention
The compound represented by the general formula (I) will be described in detail. [0010] [Formula 4] Where R₂Represents a substituent. n is 0 or more and 4
Represents the following integers: multiple n when n is 2 or more₂Is it
They can be the same or different and can be joined together to form a ring.
It may be formed. R₂Examples of groups of
Atom, halogen atom, alkyl group (cycloalkyl group,
Including bicycloalkyl groups), alkenyl groups (cycloa
Including alkenyl group and bicycloalkenyl group), alkini
Group, aryl group, heterocyclic group, cyano group, hydroxy
Group, nitro group, carboxyl group, alkoxy group, ant
Oxy group, silyloxy group, heterocyclic oxy group, a
Siloxy group, carbamoyloxy group, alkoxycal
Bonyloxy group, aryloxycarbonyloxy, a
Mino group (including alkylamino group and anilino group), reed
Ruamino group, aminocarbonylamino group, alkoxy group
Rubonylamino group, aryloxycarbonylamino
Group, sulfamoylamino group, alkyl or aryl
Sulfonylamino group, mercapto group, alkylthio group,
Arylthio group, heterocyclic thio group, sulfamoyl group,
A sulfo group, an alkyl or arylsulfinyl group, an
Alkyl or arylsulfonyl group, acyl group, aryl
Ruoxycarbonyl group, alkoxycarbonyl group, cal
Vamoyl group, aryl or heterocyclic azo group, imide
Group, phosphino group, phosphinyl group, phosphinyloxy
Ci group, phosphinylamino group, silyl group can be mentioned. The above group is further substituted with a substituent.
And the substituent includes the above-mentioned groups.
The In the following, R₂Examples of these groups will be further described. this
These groups include a hydrogen atom, a halogen atom (for example, a salt
Elementary atom, bromine atom, iodine atom), alkyl group (straight chain or
Or a branched or unsubstituted alkyl group, preferably
Or an alkyl group having 1 to 30 carbon atoms such as methyl
, Ethyl, n-propyl, isopropyl, t-butyl
Ru, n-octyl, eicosyl, 2-chloroethyl, 2
-Cyanoethyl, 2-ethylhexyl, 3- (2,4-
Di-t-amylphenoxy) propyl), cycloalk
Group (preferably substituted or unsubstituted having 3 to 30 carbon atoms)
A cycloalkyl group such as cyclohexyl, cyclo
Pentyl, 4-n-dodecylcyclohexyl and the like
A multicycloalkyl group such as a bicycloalkyl group
(Preferably substituted or unsubstituted having 5 to 30 carbon atoms
A bicycloalkyl group, for example bicyclo [1,2,
2] Heptan-2-yl, bicyclo [2,2,2] oct
Polycyclic structures such as tan-3-yl) and tricycloalkyl groups
The group of is mentioned. Preferably monocyclic cycloalkyl
Group, bicycloalkyl group, monocyclic cycloalkyl
Groups are preferred. ), An alkenyl group [straight chain or branched
Or an unsubstituted alkenyl group, preferably having 2 to 3 carbon atoms.
0 alkenyl groups such as vinyl, allyl,
Lenyl, geranyl, oleyl), cycloalkenyl groups
(Preferably substituted or unsubstituted having 3 to 30 carbon atoms
A cycloalkenyl group, for example 2-cyclopentene-
1-yl, 2-cyclohexen-1-yl)
Multicycloalkenyl groups such as bicycloalkene
Group (preferably substituted or non-substituted having 5 to 30 carbon atoms)
A substituted bicycloalkenyl group, for example, bicyclo [2,
2,1] hept-2-en-1-yl, bicyclo [2,
2,2] oct-2-en-4-yl)], and trisic
Loalkenyl group, bicycloalkenyl group, monocyclic
Cycloalkenyl groups are preferred. ) Alkynyl group
(Preferably, a substituted or unsubstituted alkenyl having 2 to 30 carbon atoms.
Alkynyl groups such as ethynyl, propargyl, trimer
Tilsilylethynyl group), An aryl group (preferably having 6 to 30 carbon atoms)
Substituted or unsubstituted aryl groups such as phenyl,
p-tolyl, naphthyl, m-chlorophenyl, o-hex
Sadecanoylaminophenyl), a heterocyclic group (preferably
Is a 5- to 7-membered substituted or unsubstituted, saturated or unsaturated
Japanese, aromatic or non-aromatic, monocyclic or condensed ring
More preferably, the ring-constituting atoms are carbon atoms.
Selected from atoms, nitrogen atoms and sulfur atoms, and
Any hetero atom of a child, oxygen atom or sulfur atom
A heterocyclic group having at least one, more preferably
Is a 5- or 6-membered aromatic hetero of 3 to 30 carbon atoms
It is a cyclic group. For example, 2-furyl, 2-thienyl, 2-
Pyridyl, 4-pyridyl, 2-pyrimidinyl, 2-ben
Zothiazolyl), cyano group, hydroxyl group, nitro
Group, carboxyl group, Alkoxy group (preferably having 1 to 3 carbon atoms)
0 substituted or unsubstituted alkoxy groups such as
Toxi, ethoxy, isopropoxy, t-butoxy, n
-Octyloxy, 2-methoxyethoxy), aryl
An oxy group (preferably a substitution of 6 to 30 carbon atoms or
Unsubstituted aryloxy groups such as phenoxy, 2
-Methylphenoxy, 2,4-di-t-amylphenoxy
4-t-butylphenoxy, 3-nitrophenoxy
Si, 2-tetradecanoylaminophenoxy), silyl
An oxy group (preferably silyloxy having 3 to 20 carbon atoms)
Groups such as trimethylsilyloxy, t-butyldi
Methylsilyloxy), heterocyclic oxy group (preferably
Is a substituted or unsubstituted heterocyclic ring having 2 to 30 carbon atoms.
In the xy group, the heterocyclic moiety was explained in the above heterocyclic group
Heterocyclic moieties are preferred, for example 1-phenyltetrazo
-5-oxy, 2-tetrahydropyranyloxy
B) Acyloxy group (preferably formyloxy
Si group, substituted or unsubstituted alkyl having 2 to 30 carbon atoms
Carbonyloxy group, substituted or unsubstituted 6 to 30 carbon atoms
Substituted arylcarbonyloxy group, for example
Lumiloxy, acetyloxy, pivaloyloxy,
Thearoyloxy, benzoyloxy, p-methoxyph
Enylcarbonyloxy), carbamoyloxy group (preferably
Preferably, a substituted or unsubstituted carbon having 1 to 30 carbon atoms.
A vamoyloxy group, for example, N, N-dimethylcarba
Moyloxy, N, N-diethylcarbamoyloxy,
Morpholinocarbonyloxy, N, N-di-n-octy
Ruaminocarbonyloxy, Nn-octylcarbamo
Yloxy), alkoxycarbonyloxy group (preferred
Or substituted or unsubstituted alkoxy having 2 to 30 carbon atoms
A carbonyloxy group such as methoxycarbonyloxy
Si, ethoxycarbonyloxy, t-butoxycarboni
Ruoxy, n-octylcarbonyloxy), aryl
Oxycarbonyloxy group (preferably having 7 to 3 carbon atoms)
0 substituted or unsubstituted aryloxycarbonylo
A xy group such as phenoxycarbonyloxy, p-
Methoxyphenoxycarbonyloxy, pn-hexa
Decyloxyphenoxycarbonyloxy), Amino group (preferably amino group, carbon number
1-30 substituted or unsubstituted alkylamino groups, charcoal
Substituted or unsubstituted arylamino having 6 to 30 primes
A heterocyclic amino group having 0 to 30 carbon atoms, for example
Amino, methylamino, dimethylamino, anili
N-methyl-anilino, diphenylamino, N-
1,3,5-triazin-2-ylamino), acyla
Mino group (preferably formylamino group, 1 to 3 carbon atoms)
0 substituted or unsubstituted alkylcarbonylamino
A substituted or unsubstituted aryl group having 6 to 30 carbon atoms
A sulfonylamino group such as formylamino,
Cetylamino, pivaloylamino, lauroylamino,
Benzoylamino, 3,4,5-tri-n-octylo
Xyphenylcarbonylamino), aminocarbonyla
Mino group (preferably substituted or unsubstituted 1 to 30 carbon atoms)
Substituted aminocarbonylamino groups such as carbamoyl
Ruamino, N, N-dimethylaminocarbonylamino,
N, N-diethylaminocarbonylamino, morpholino
Carbonylamino), alkoxycarbonylamino group
(Preferably a substituted or unsubstituted alkyl having 2 to 30 carbon atoms
A alkoxycarbonylamino group such as methoxycarbo
Nylamino, ethoxycarbonylamino, t-butoxy
Carbonylamino, n-octadecyloxycarbonyl
Amino, N-methyl-methoxycarbonylamino), Aryloxycarbonylamino group (preferably
Or a substituted or unsubstituted aryl having 7 to 30 carbon atoms
A ruoxycarbonylamino group, for example phenoxyca
Rubonylamino, p-chlorophenoxycarbonylamino
, Mn-octyloxyphenoxycarbonylamino
B), a sulfamoylamino group (preferably having 0 carbon atoms)
~ 30 substituted or unsubstituted sulfamoylamino groups
For example, sulfamoylamino, N, N-dimethyl
Aminosulfonylamino, Nn-octylaminosulfur
Phonylamino), alkyl and arylsulfonylamino
Group (preferably substituted or unsubstituted having 1 to 30 carbon atoms)
Alkylsulfonylamino group of 6 to 30 carbon atoms
Or an unsubstituted arylsulfonylamino group,
For example, methylsulfonylamino, butylsulfonyla
Mino, phenylsulfonylamino, 2,3,5-trick
Lolophenylsulfonylamino, p-methylphenyls
Sulfonylamino), mercapto group, An alkylthio group (preferably having a carbon number of 1
30 substituted or unsubstituted alkylthio groups, for example
Methylthio, ethylthio, n-hexadecylthio), a
A reelthio group (preferably a substitution of 6 to 30 carbon atoms or
Is an unsubstituted arylthio group such as phenylthio,
p-chlorophenylthio, m-methoxyphenylthio
E) a heterocyclic thio group (preferably a group having 2 to 30 carbon atoms)
A substituted or unsubstituted heterocyclic thio group, wherein the heterocyclic moiety is
The heterocyclic group described in the heterocyclic group of
2-benzothiazolylthio, 1-phenyltetrazo
-5-ylthio), sulfamoyl group (preferably
C0-30 substituted or unsubstituted sulfamoyl
Groups such as N-ethylsulfamoyl, N- (3-
Dodecyloxypropyl) sulfamoyl, N, N-di
Methylsulfamoyl, N-acetylsulfamoyl,
N-benzoylsulfamoyl, N- (N′-phenyl)
Carbamoyl) sulfamoyl), sulfo group, Alkyl or arylsulfinyl groups
(Preferably, a substituted or unsubstituted atom having 1 to 30 carbon atoms.
Ruylsulfinyl group, 6-30 substituted or unsubstituted
An arylsulfinyl group, for example methylsulfur
Ynyl, ethylsulfinyl, phenylsulfinyl,
p-methylphenylsulfinyl), alkyl or a
A reelsulfonyl group (preferably a group having 1 to 30 carbon atoms)
Substituted or unsubstituted alkylsulfonyl groups, 6-30 positions
A substituted or unsubstituted arylsulfonyl group, for example
Methylsulfonyl, ethylsulfonyl, phenyls
Sulfonyl, p-methylphenylsulfonyl), acyl group
(Preferably a formyl group, a C2-C30 substitution or
Unsubstituted alkylcarbonyl group, substitution of 7 to 30 carbon atoms
Or an unsubstituted arylcarbonyl group, for example
Acetyl, pivaloyl, 2-chloroacetyl,
Aroyl, benzoyl, pn-octyloxypheny
Rucarbonyl), aryloxycarbonyl group (preferably
Or substituted or unsubstituted aryl having 7 to 30 carbon atoms
An oxycarbonyl group such as, for example, phenoxycarboni
, O-chlorophenoxycarbonyl, m-nitrofe
Noxycarbonyl, pt-butylphenoxycarboni
Le), An alkoxycarbonyl group (preferably carbon
Substituted or unsubstituted alkoxycarbons having 2 to 30 prime numbers
Group, for example, methoxycarbonyl, ethoxycarbo
Nyl, t-butoxycarbonyl, n-octadecyloxy
Cicarbonyl), a carbamoyl group (preferably carbon number)
1-30 substituted or unsubstituted carbamoyl, eg
For example, carbamoyl, N-methylcarbamoyl, N, N-
Dimethylcarbamoyl, N, N-di-n-octylcal
Vamoyl, N- (methylsulfonyl) carbamoyl),
An aryl or heterocyclic azo group (preferably having 6 to
30 substituted or unsubstituted arylazo groups, 3 carbon atoms
To 30 substituted or unsubstituted heterocyclic azo groups (hetero
The ring portion is preferably the heterocyclic portion described in the above heterocyclic group.
For example, phenylazo, p-chlorophenyla
Zo, 5-ethylthio-1,3,4-thiadiazole-2
-Ylazo), an imide group (preferably having 2 to 30 carbon atoms)
Substituted or unsubstituted imide groups such as N-succi
Imide, N-phthalimide), phosphino group (preferred
Or substituted or unsubstituted phosphines having 2 to 30 carbon atoms.
Group such as dimethylphosphino, diphenylphosphine
Ino, methylphenoxyphosphino), phosphinyl group
(Preferably substituted or unsubstituted having 2 to 30 carbon atoms
Phosphinyl group, for example phosphinyl, dioctyl
Oxyphosphinyl, diethoxyphosphinyl), Phosphinyloxy group (preferably carbon
A substituted or unsubstituted phosphinyloxy having a number of 2 to 30
A group such as diphenoxyphosphinyloxy, geo
Octyloxyphosphinyloxy), phosphinylamino
Group (preferably substituted or unsubstituted having 2 to 30 carbon atoms)
A substituted phosphinylamino group such as dimethoxyphos
Finylamino, dimethylaminophosphinylami
B), a silyl group (preferably having 3 to 30 carbon atoms)
Or an unsubstituted silyl group such as trimethylsilyl.
, T-butyldimethylsilyl, phenyldimethylsilyl
Le). Of the above groups having a hydrogen atom
May be removed and further substituted with the above groups.
Yes. Examples of such groups include alkylcarbonyl groups.
Minosulfonyl group, arylcarbonylaminosulfonate
Group, alkylsulfonylaminocarbonyl group, aryl
A rusulfonylaminocarbonyl group, specifically
Is methylsulfonylaminocarbonyl, p-methylphenyl
Enylsulfonylaminocarbonyl, acetylaminos
Examples include sulfonyl and benzoylaminosulfonyl. In the general formula (I), R₁Replace or
Represents an unsubstituted alkyl group or an aryl group. R₁But
Examples of the substituent that may be present include the R₂Examples of substituents for
As mentioned above. Preferably R₁Is substituted or unsubstituted
It is an alkyl group. R₁When the total number of carbon atoms is an alkyl group
12 or more and 60 or less are preferable, and 16 or more and 50 or less are more preferable.
Preferably, 18 or more and 40 or less are more preferable. Also a
In the case of a reel group, it is preferably 6 or more and 60 or less, and 16 or more and 5
0 or less is more preferable, and 18 or more and 40 or less is more preferable.
That's right. In general formula (I), n is an integer of 0 or more and 4 or less
Represents. n is preferably 0 to 2, more preferably 0.
Or 1, particularly preferably 0. Next, the general formula of the present invention
The compound represented by (II) will be described in detail. [0027] [Chemical formula 5] In the general formula (II), R₂And n is one
Represents and prefers the same as described in general formula (I)
The same applies to the new range. Next, in the general formula (III) of the present invention,
The compounds represented will be described in detail. [0029] [Chemical 6] In the general formula (III), R₂And n is
Represents the same as described in general formula (I).
The preferred range is the same. A was protected by a protecting group
Represents an amino group. Common protecting groups include, for example, a
Lucoxycarbonyl group (eg, methoxycarbonyl, ethyl
Toxoxycarbonyl, t-butoxycarbonyl, benzyl
Oxycarbonyl, 2-trimethylsilylethoxycal
Bonyl, formyl, acyl groups (eg acetyl, chloro
Roacetyl, benzene-1,2-dicarbonyl), ben
Zyl group, alkylidene group (for example, benzylidene), sulfur
Phonyl groups such as methanesulfonyl, p-toluenesulfur
Honyl) and the like. Therefore, as A,
Killoxycarbonylamino group, alkenyloxycal
Bonylamino group, cycloalkyloxycarbonylamino
Group, aryloxycarbonylamino group, heterocyclic o
Xyloxycarbonylamino, formylamino, acyl
Mido group, imide group, benzylamino group, sulfonamide
Groups and the like. Furthermore, T.W. W. Greene
  and P.M. G. M.M. Co-authored by Wuts “Pro
Protective Groups in Organic
  Synthesis Third Editio
n ", John Wiley & Sons (199
The protecting group described in Chapter 7 (pages 494 to 653) of 9) is preferred.
Preferably, an amino group protected with the protecting group is also preferred in the present invention.
Can be cited as a good A. In the present invention
A is preferably a cyclic imide group, more preferably
Is represented by the following general formula (VII) or general formula (VIII),
It is a cyclic imide group represented by (IX). [0031] [Chemical 7] Where Z₁, Z₂Are each independently an oxygen atom,
-N (R₁₁)-Group, or -C
(R₁₂) (R₁₃)-Represents a group represented by-. here
And R₁₁, R₁₂And R₁₃Are independently hydrogen fields
Or a substituted or unsubstituted alkyl group or aryl
Represents a group. Z₃Is necessary to form a 5- to 7-membered ring
Represents a nonmetallic atom group. R₁₄, R₁₅Are each independently water
An elementary atom, or a substituted or unsubstituted alkyl group,
Represents a diol group. In the general formula (VII), Z₁Is oxygen
In the case of atoms, Z₂Is -C (R₁₂) (R ₁₃)-
It is preferred that Smell in general formula (VIII)
Z₃The 5- to 7-membered ring formed by
Zen, or 5- or 7-membered nitrogen, oxygen, or sulfur atoms
An unsaturated heterocycle containing at least one (eg, pillow
, Pyrazole, imidazole, 1,2,3-triazo
Oxazole, thiazole, isoxazole,
Isothiazole, furan, thiophene, pyridine, pyra
Gin, Pyrimidine, Pyridazine, Azepine, Oxepi
And the like. Preferably benzene ring
It is. These rings may further have a substituent, and
As a substituent, R₂And the substituents mentioned in the above. next
The compound represented by formula (IV) of the present invention will be described in detail.
The [0033] [Chemical 8] In the general formula (IV), R₂And n is one
Represents and prefers the same as described in general formula (I)
The same applies to the new range. A is described in general formula (III).
It represents the same thing as the solid one, and the preferred range is the same.
The X is a halogen atom (fluorine, chlorine, bromine, iodine)
Represents. Next, the compound represented by the general formula (V) of the present invention is
This will be described in detail. [0035] [Chemical 9] In the general formula (V), R₁Is the general formula
Represents the same as described in (I), preferably
The range is the same. Next, it is represented by the general formula (VI) of the present invention.
The compound will be described in detail. [0037] Embedded imageIn the general formula (VI), R₁, R₂and
n represents the same as described in the general formula (I).
The preferred range is also the same. A in general formula (III)
Represents the same as described above, and the preferred range is also the same.
It is like. Next, the production method of the present invention will be described in detail.
To do. Preparation of the compound represented by the general formula (I) of the present invention
The manufacturing method comprises the following steps 1) to 4). 1) Preserving the amino group of the compound represented by the following general formula (II)
It is represented by the following general formula (III) by the reaction protected with a protective group.
For synthesizing compounds 2) The sulfo group of the compound represented by the general formula (III)
Rogenated to synthesize compounds represented by the following general formula (IV)
Process 3) The compound represented by the general formula (IV) and the following general formula
The compound represented by (V) is represented by the following general formula (VI).
Of synthesizing compounds 4) Deprotecting the compound represented by the general formula (VI)
Step of synthesizing a compound represented by the general formula (I) The above production method is represented by the following reaction scheme.
It is. In each step, the product is removed once and purified.
You can put your work, or you can connect it to the next process without taking it out
good. [0040] Embedded image Next, the manufacturing method in each process will be described in detail.
I will explain. The production method of the present invention is particularly suitable for production routes.
It has a sign. Step 1) The amino group of the compound represented by the general formula (II) is represented by the general formula
Convert to the protected amino group in (III),
That is, to synthesize the compound represented by the general formula (III)
Are various acylating agents (acyl halides, acid anhydrides,
Esters), sulfonating agents (alkyl or amines)
Reel sulfonic acid halides), benzyl halide
(Benzyl chloride, benzyl chloride, etc.) etc.
These various protecting group-introducing reagents are used. Table in general formula (III)
A cyclic group which is a preferred group as A
Imido groups, especially the groups represented by the above (VII) to (IX)
HOOC-Z corresponding to this group₁-Z₂
-COOH, 2nd and 3rd positions
Each carbon atom) is Z₃Bound HOOC-C = C
-COOH, HOOC-C (R₁₄) = C (R₁₅) −
COOH acid anhydride, dihalide or diester
Preferably used. Protecting group-introducing reagents for these amino groups
Is generally 1 for the compound represented by formula (II)
Used in a molar ratio of 00: 1 to 1: 100, preferably
10: 1 to 1:10 molar ratio, more preferably 5: 1 to
1: 5 molar ratio, more preferably 1: 1 to 1: 3
The ratio. Compounds represented by general formula (II) and protecting group
The reaction with the reagent is preferably performed in the presence of a base. salt
As the group, various inorganic bases and organic bases can be used.
For example, LDA (lithium diisopropylamino
Do), sodium hydride, sodium hydroxide, potassium hydroxide
Lithium, potassium carbonate, sodium carbonate, potassium te
rt-butoxide, sodium tert-butoxide,
Triethylamine, diisopropylethylamine, DB
U (1,8-diazabicyclo [5.4.0] -7-un
Decene), pyridine, 2,6-lutidine and the like are used.
The Preferably, potassium carbonate, sodium hydroxide,
Riethylamine and pyridine are used, particularly preferably
Triethylamine and pyridine are used. Use of base
The amount is 1 mol of the compound represented by the general formula (II).
0.1-20 mol, preferably 0.5-10 mol, more
Preferably 1-3 mol is used. Table in general formula (III)
The resulting compounds may form salts with these bases.
The Therefore, in the present invention, it is represented by the general formula (III).
The compound that contains the sulfonate salt of the compound
is there. The reaction may be carried out without a solvent, but preferably
May be carried out by dissolving or dispersing in a suitable solvent. Main departure
Examples of the solvent that can be used for the light reaction include
Water, alcoholic solvents (eg methanol, isopropyl
Panol, t-butyl alcohol), chlorinated solvents (eg
Dichloromethane, chloroform), aromatic solvents (eg
For example, benzene, toluene, chlorobenzene), amide
System solvents (for example, N, N-dimethylformamide,
N, N-dimethylacetamide), ureido solvents (examples)
1,3-dimethyl-2-imidazolidinone), Nito
Ril solvents (eg acetonitrile), ether solvents
Medium (eg, diethyl ether, tetrahydrofuran)
), Sulfone solvents (for example, sulfolane), sulfo
Xoxide solvents (eg dimethyl sulfoxide), phosphorus
Acid amide solvents (eg hexamethylphosphoric acid
Lyamide), hydrocarbon solvents (eg, hexane,
Hexane). Preferably, a chlorinated solvent,
Aromatic solvents, amide solvents, ureido solvents, Nitori
Solvent, alcohol solvent, sulfone solvent, phosphoric acid
Amide solvents and hydrocarbon solvents are used, especially preferred.
Or aromatic solvents, amide solvents, nitrile solvents,
Alcohol solvents and sulfone solvents are used. Genuine
The reaction temperature is not particularly limited, but from −50 ° C.
It can be carried out in the range of 200 ° C, preferably -10 ° C
To 100 ° C., particularly preferably 0 ° C.
In the range of 80 ° C. As reaction time of this reaction
There is no particular restriction, but it is carried out in the range of 1 minute to 50 hours
Preferably 1 minute to 20 hours.
Range, more preferably in the range of 5 minutes to 10 hours.
The Step 2) Halogenation of the sulfonic acid represented by the general formula (III)
Phosphorus pentachloride, phosphoryl chloride, chlorosulfuric acid, benzotri
The method using chloride and thionyl chloride is generally used.
It is preferably used in the present invention. Also,
Pyridinium salt of sulfonic acid represented by general formula (III)
A method of reacting phosphorus pentachloride with thionyl chloride
Preferably applied. Reaction conditions such as molar ratio and temperature
Is in accordance with the conditions of step 1) described above. Step 3) The compound represented by the general formula (VI) is represented by the general formula (IV).
And a compound represented by the general formula (V)
Can be. The base used in the reaction is a general formula
The compound represented by (V) itself may be used, but preferably
Is an inorganic base such as potassium carbonate or sodium carbonate
Or tertiary amines or organic bases such as pyridines
Are preferably used. These compounds against each other
The reaction conditions such as molar ratio and temperature are the same as those described in 1) above.
According to the matter. Step 4) The compound represented by the general formula (I) is represented by the general formula (IV).
Obtained by deprotection reaction from the compound to the amino group
The Regarding these deprotections, each protecting group
Preferred deprotecting agents are different. For example, in general formula (IV)
A is a cyclic imide group, preferably the aforementioned general formula (VI
I) to (IX) (for example, A is a group represented by
Talimide) and hydrazine can be easily deprotected
is there. The molar ratio of these compounds to each other, temperature, etc.
The reaction conditions are the same as those for the process 1) described above. The following compounds of the general formula (I)
Although a specific example is shown, this invention is not limited to these.
Absent. [0049] Embedded image[0050] Embedded imageThe following compounds of the general formula (II)
Although a specific example is shown, this invention is not limited to these.
Absent. [0052] Embedded imageThe following compounds represented by the general formula (III)
Specific examples are shown below, but the present invention is not limited to these.
There is no. [0054] Embedded imageThe following are compounds of the general formula (IV)
Although a specific example is shown, this invention is not limited to these.
Absent. [0056] Embedded imageThe following are compounds of the general formula (V)
Although a specific example is shown, this invention is not limited to these.
Absent. [0058] Embedded imageThe following are compounds of the general formula (VI)
Although a specific example is shown, this invention is not limited to these.
Absent. [0060] Embedded image[0061] Embedded imageIn the following description, it is shown above.
When referring to each exemplified compound,
By using the number (x) in parentheses attached,
(X) "is displayed. [0063] The following examples further illustrate the present invention.
However, the present invention is not limited to this. Example 1 Example Compound (I-1)
Completion [Step 1] Synthesis of Exemplified Compound (III-1) Example Compound (II-1) 5.0 g
Dissolved in L, and 4.28 g of phthalic anhydride at room temperature
2.57 mL of gin, catalytic amount of 4-dimethylaminopyrid
Added. After stirring at 50 ° C for 1 hour, cool to room temperature
On the other hand, when concentrated, a white precipitate was obtained. Example after filtration and drying
10.3 g of the compound (III-1) shown as a pyridine salt
(93.2%) was obtained.¹H-NMR (300 MHz, D
MSO-d ⁶, TMS) δ: 10.9 (s, 1H),
8.9 (d, 2H), 8.6 (t, 1H), 8.4
(D, 1H), 8.1 (t, 2H), 7.8 (d, 1H)
H), 7.7-7.5 (m, 4H), 7.4 (t, 1
H), 7.1 (1H). [Step (2)] Example Compound (IV-1)
Composition 5.0 g of Exemplified Compound (III-1) in 25 mg of acetonitrile
Dissolve in mL and gradually add 3.27 g of phosphorus pentachloride to room temperature.
Added. Stir for 4 hours under reflux, then cool to room temperature
It was. The resulting white precipitate was collected by filtration to give Exemplified Compound (IV-1)
Of 2.90 g (69.0%). [Step (3)] Example Compound (VI-1)
Composition Example Compound (V-1) 0.50 g
Dissolve in mL and add 0.33 mL of triethylamine.
Furthermore, 0.5 g of exemplary compound (IV-1) was added and the temperature was increased to 60 ° C.
And stirred for 1 hour. The resulting white precipitate was collected by filtration and acetonit
0.55 g of Exemplified Compound (VI-1) by recrystallization from ril
(64.0%) was obtained.¹H-NMR (300 MHz, C
DCI₃, TMS) δ: 8.1 (dd, 1H), 7.9
(Dd, 2H), 7.8 (dd, 2H), 7.7-7.
6 (m, 2H), 7.4 (dd, 1H), 5.1 (t,
1H), 3.0 (m, 2H), 1.5 (m, 4H),
1.3 (m, 28H), 0.9 (t, 3H). [Step 4]] of the exemplified compound (I-1)
Composition 1.0 g of exemplified compound (VI-1) in 10 mL of methanol
Dissolve, add 0.3 mL of hydrazine monohydrate,
Stir for 2 hours at ° C. After concentration, the residue is subjected to column chromatography.
The exemplified compound (I-1) was purified by chromatography.
55 g (72%) were obtained.¹H-NMR (300 MHz,
CDCl₃, TMS) δ: 7.70 (d, 1H), 7.
30 (t, 1H), 6.80 (m, 2H), 4.80
(Brs, 2H), 4.70 (brt, 1H), 2.9
0 (m, 2H), 1.40 (m, 2H), 1.20
(M, 30H), 0.90 (t, 3H). As is apparent from the above steps, each step and
Is a raw material that is easy to obtain.
Sulfonamide compounds can be produced and
Excellent operability and post-treatment operability after reaction.
It turns out that this is a highly productive manufacturing route. [0069] According to the present invention, it is easy to obtain a raw material.
In various yields, various orthoaminobenzenesulfones
A method for producing a large amount of a mid compound can be provided.

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Claims (1)

What is claimed is: 1. A process for producing a sulfonamide compound represented by the following general formula (I), comprising the following steps 1) to 4): 1) Step of synthesizing a compound represented by the following general formula (III) by a reaction of protecting the amino group of the compound represented by the following general formula (II) with a protecting group 2) represented by the general formula (III) A step of synthesizing a compound represented by the following general formula (IV) by halogenating the sulfo group of the compound: 3) a compound represented by the general formula (IV) and a compound represented by the following general formula (V): Step 4 for synthesizing a compound represented by the following general formula (VI) 4) Step for synthesizing a compound represented by the following general formula (I) by deprotecting the compound represented by the general formula (VI) 1] In the general formulas (I), (V) and (VI), R ₁ represents a substituted or unsubstituted alkyl group or aryl group. In the general formulas (I) to (IV) and (VI), R ₂
Represents a substituent. n represents an integer of 0 or more and 4 or less. When n is 2 or more, the plurality of R ₂ may be the same or different, and may be bonded to each other to form a ring. In the general formulas (III), (IV) and (VI), A represents a protected amino group. In general formula (IV), X represents a halogen atom.