JPH0479349B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to novel pyrazolo[1,5-b][1,
2,4] relates to a method for producing a triazole derivative. (Background of the Invention) A nitrogen atom at the bridgehead position, at least two in total, capable of interacting with 10 π electrons including the lone pair of this nitrogen atom and another nitrogen atom,
General formula with up to 6 nitrogen atoms ...; Indicates three double bonds that can be moved.・; Indicates nitrogen or carbon atom. The 5-5 fused polycyclic compound represented by is commonly called "azapentalene". Until now, this compound has been studied mainly from structural chemistry, interest as a organizing active substance, and interest as a magenta coupler in photochemistry (J. Elgureo,
R. Jacquier, S. Mignonac-Mondon, J.
Heterocyclic.Chem., 10 , 411 (1973), H. Koga,
M.Hirobe, T.Okamoto, Chem.Pharm.Bull.,
22, 482 (1974), J.Bailey, JCSPerkin I2047
(1977), Japanese Patent Publication No. 1977-27411, Japanese Patent Publication No. 129586, 1977
(see issue, etc.). The present inventors have conducted various studies on methods for synthesizing such azapentalene compounds, and as a result, they have succeeded in producing azapentalene compounds with novel skeletons by cyclization condensation of certain N-aminotriazolium salts and acid anhydrides. It has been found that the compound exhibits extremely excellent properties as a magenta coupler for color photography, and based on this knowledge, the present invention has been completed. (Structure of the invention) That is, the present invention comprises: 1. General formula (In the formula, R ₁ represents a hydrogen atom, an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group, R ₂ represents an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group, and X represents an acid group. ) and the general formula (R ₃ CO) ₂ O or (In the formula, R ₃ represents a hydrogen atom, an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group.) (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) 7-acylated pyrazolo [1,5-
b] [1,2,4]triazole was obtained, and the 7-position acyl group of this compound was deacylated to give the general formula (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) Pyrazolo[1,5-b][1,2,
4] Obtain a triazole derivative and reduce the 1-position of this compound to form the general formula (In the formula, R ₁ and R ₃ have the same meanings as above.)
A method for producing a pyrazolo[1,5-b][1,2,4]triazole derivative, characterized in that the compound is a compound represented by the following general formula: (In the formula, R ₁ represents a hydrogen atom, an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group, and R ₂ represents an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group.) The compound is N-aminated to form the general formula (In the formula, R ₁ and R ₂ have the same meanings as above.
X represents an acid radical. ) was obtained, and this N-aminotriazolium salt was subjected to cyclization condensation with an acid anhydride represented by the general formula () in the same manner as in the method of item 1) above. , 7 expressed by the general formula ()
-Acylated pyrazolo[1,5-b][1,2,4]
A triazole is obtained, the 7-position acyl group is deacylated to obtain a pyrazolo[1,5-b][1,2,4]triazole derivative represented by the general formula (), and this 1-position is reduced. , a method for producing a pyrazolo[1,5-b][1,2,4]triazole derivative, which comprises obtaining a compound represented by the general formula (). It provides: The above general formula (), (), (), (), ()
and R ₁ and R ₃ in the compound represented by ()
Alkyl groups include lower alkyl groups such as methyl, ethyl, propyl, and butyl groups to higher alkyl groups having up to 22 carbon atoms, such as pentyl group, hexyl group, heptyl group, octyl group, decyl group, undecyl group, and tridecyl group. group, octadecyl group, etc., and may be linear or branched. In particular, R ₁ is preferably a methyl group. Aryl groups for R ₁ and R ₃ include phenyl and naphthyl groups, and substituted alkyl groups include benzyl and
Examples of the substituted aryl group include a phenethyl group, and examples of the substituted aryl group include a halogenophenyl group, a nitrophenyl group, a cyanophenyl group, and an alkoxyphenyl group. In addition, these R ₁ and R ₃ are groups inert to the reaction,
For example, it may have an alkoxyl group, a nitro group, a cyano group, a halogen atom, etc. as a substituent. Next, as the alkyl group of R ₂ in the compounds represented by the above general formulas () and (), methyl group,
It includes lower alkyl groups such as ethyl, propyl, and butyl groups, and higher alkyl groups such as pentyl, hexyl, and dodecyl groups.Aryl groups include phenyl and naphthyl groups, and substituted alkyl groups include benzyl groups. , phenethyl group, p-methoxyphenylmethyl group, m-nitrophenylmethyl group, etc., and these include groups that are inert to the same reaction as R ₁ and R ₃ as substituents. good. In particular, when R ₂ is an optionally substituted benzyl group, the substituent can be easily removed reductively in a later step, which is advantageous when producing the 1H-form. In the above general formula (), the acid group of X is an acid group,
For example, halogen anions such as chlorine, bromine, and iodine, NO ³ , SO ^2- ₄ , [Formula] [Formula] [Formula] [Formula], etc. are included. Note that the pyrazolo[1,5-b][1,2,4]triazole derivative obtained by the method of the present invention further has a substituent as described above on the R ₁ , R ₂ or R ₃ group. The compound can be obtained directly according to the reaction scheme described below, but in this step, the basic skeleton of the present invention, pyrazolo-[1,5-
b] After forming a [1,2,4]triazole ring, a desired substituent may be derived through a subsequent reaction. If necessary, the 7-position is an acyl group, R ₂
may be derived with a compound having a protecting group such as a benzyl group. For example, as shown in Example 6 below, the amino groups of compounds 11-- of the present invention can be derived into acid anilides 13-, etc. by a known method. The reaction process of the method of the present invention is as follows when X in the general formula () is an iodine ion. In addition, the general formula () obtained by the method of the present invention
A coupling-off group known in photographic couplers may be introduced into the 7-position of the compound represented by the formula to form a photographic coupler. This is shown in the step ()→() in the reaction process below. Reaction equation Hereinafter, embodiments of the method of the present invention will be described according to the above reaction scheme. In the present invention, the triazole compound () can be easily obtained by reacting an oxadiazole () with an organic primary amine (). The reaction temperature is usually 50
Start at a temperature of ~150°C and complete under conditions where the water produced by the dehydration reaction gently refluxes. The reaction time is usually in the range of 0.1 to 6 hours, but is not limited thereto. In addition, oxadiazole is Ber., Vol. 32, 797
(1899). Next, the synthesis of N-aminotriazolium salt () by amination of the triazole compound () is as follows:
This can be carried out using hydroxylamine-O-sulfonic acid, O-(2,4-dinitrophenyl)hydroxylamine, or O-diphenylphosphorylhydroxylamine as an aminating agent. Other aminating agents that can be used in the present invention include Y.
Tamuraet, al., Synthesis, 1977, 1-17 and the references therein. This amination reaction is usually carried out at a reaction temperature of 0°C to 100°C for 0.1 to 5 hours. The molar ratio of the triazole compound to the aminating agent is generally 1:1, but the cheaper one of the two may be used in excess. The cyclization condensation reaction between the N-aminotriazolium salt () and the acid anhydride () is carried out in the presence of a base. As the base, amines, sodium acetate, sodium propionate, etc. can be used. In this reaction, it is desirable to use at least 3 equivalents of the acid anhydride and at least 5 equivalents of the base based on the N-aminotriazolium salt. If the amounts of acid anhydride and base are less than this lower limit, the reaction yield will decrease. This is considered to be because when the acid anhydride content is less than the above-mentioned lower limit, a side reaction that does not give the target product from the reaction intermediate proceeds. The reaction temperature is generally 100
℃~180℃ can be used, but 120℃ or higher is preferable.
The reaction time varies depending on the type and amount of acid anhydride.
There is no particular limit, but it generally ranges from 0.5 to 20 hours. The reaction solvent may be any inert solvent; for example, dimethylformamide (DMF), dimethylacetamide, N-methylpyrrolidone, etc. are commonly used; however, when lower acid anhydrides are used as reaction components, An excess amount of this can also be used as a solvent. Specific examples of acid anhydrides include formic anhydride,
Acetic anhydride, propionic anhydride, lauric anhydride,
Examples include benzoic anhydride, methoxycarbonylpropionic anhydride, ethoxycarbonylpropionic anhydride, and 4-(p-nitrophenyl)butyric anhydride. Further, the acid anhydride of the above general formula () also includes mixed acid anhydrides, and a preferred example in this case is a mixed acid anhydride with trimethyl acetic acid. Compound () is obtained by deacylating 7-acylated pyrazolo[1,5-b][1,2,4]triazole (), which is the product of this cyclization condensation reaction. Deacylation can be achieved by heating under reflux in an aqueous solution containing a solvent boiling at room temperature to 200° C., such as ethanol, under acidic conditions using a mineral acid, according to a general method. After returning this to neutrality, the target product is isolated by extraction or the like, and purified if necessary. Note that the deacylation reaction may be performed simultaneously with the nitrosation at the 7-position. Next, by reduction of the compound (), the substituent R ₂ bonded to the 1-position nitrogen atom is removed to obtain the 1H-pyrazolo[1,5-b][1,2,4]triazole compound (). . It is desirable to select a substituent R ₂ that can be suitably removed by this reduction treatment. Such protective groups are described, for example, by Mcomie, Protective Groups in Organic
Chemistry (1973, published by Plenum) or T.
By W. Green Protective Groups in Organic
Synthesis (1981, published by Wiley-Interscience)
are often described. _Among these _{, R2} preferable for use _in the present invention is _-CH2C6H5 , -CH( _C6H5 ) _{2 , -CH2C6H3-3,4- ( OCH3} ) ₂ , _{-CH2C6H4- o} - _NO2 , _-CH2C6H4 -p- _OCH3 , -CH( _{C6H4 - p - OCH3} ) ₂ , _{-CH2-2 -} pyridyl -N-oxide and the like. Reaction conditions for removing these substituents R ₂ include catalytic reduction or reduction with an alkali metal. For example,
Palladium black/hydrogen, palladium-carbon/hydrogen,
Examples include palladium-alumina/hydrogen, sodium/liquid ammonia, and lithium/liquid ammonia. Among them, sodium metal/liquid ammonium gives a high yield. Although the desired compound obtained in each step of the above reaction process may be subjected to the subsequent reaction without being isolated in any way, it is usually isolated and purified by appropriate isolation means. Examples of such methods include solvent extraction,
Recrystallization method, filtration method, column chromatography,
Examples include thin layer chromatography. Next, pyrazolo[1,5-b][1,2,4] represented by the above general formulas (), () and ()
Specific examples of triazole derivatives are illustrated below, but it goes without saying that the present invention is not limited thereto. However, among the exemplified compounds below, 4, 14, 16, 17-
20 represents a compound obtained by further introducing a coupling-off group of a photographic coupler into the 7-position of the 1H-pyrazolo[1,5-b][1,2,4]triazole derivative, which is the object compound of the present invention. , is shown as a reference compound. (Effects of the Invention) According to the present invention, pyrazolo[1,5-b][1, 2,4] triazole derivatives can be produced. Furthermore, the compound of the present invention has the possibility of being used as a physiologically active substance, and can also be used as an intermediate for pharmaceutical production. (Examples) Next, the present invention will be described in more detail based on Examples. Example 1 (Synthesis of Exemplary Compounds 1-, 2-, 3-) (A) Synthesis of 1-amino-4-benzyl-3,5-dimethyltriazolium iodide () In the following examples, unless otherwise specified, () represents this 1-amino-4-benzyl-
3,5-dimethyltriazolium iodide was used. () 19 g (0.19 mol) of 2,5-dimethyl-1,3,4-oxadiazole () obtained by thermal decomposition of tetraacetylhydrazine and 31 g (0.29 mol) of benzylamine were reacted at 110°C for 4 hours, 4-benzyl-3,5-dimethyl-1,2,
26 g of 4-triazole () was obtained. Yield 73%,
Melting point 125-127℃. Hydroxylamine-O-sulfonic acid 66g
(0.58mol) and potassium hydroxide 40g (85%,
Hydroxylamine prepared from
An aqueous solution of potassium O-sulfonate and 75 g (0.4 mol) of the above triazole () were reacted at 80 to 90°C for 6 hours, and after returning to room temperature, the pH was adjusted to 8 to 9 with a 50% aqueous potassium carbonate solution. The generated potassium sulfate was filtered off, and the filtrate was extracted three times with chloroform. 44 g (59%) of the starting material triazole was recovered from this chloroform extract. The aqueous layer was brought to pH 3 with a 57% aqueous hydriodic acid solution under ice cooling, and crystals were precipitated. By filtering this crystal and recrystallizing it from ethanol at -20℃, 39 g of
(31%) was obtained as pale yellow crystals. () O-(2,4-dinitrophenyl)hydroxylamine as an aminating agent (J.Org.
Chem.38 1239 (1973)) was used to synthesize () as follows. Add 35 g (0.19 mol) of 4-benzyl-1,2,4-triazole () to 300 ml of dichloroethane, stir vigorously while heating to 70°C, and add O.
25 g (0.13 mol) of -(2,4-dinitrophenyl)hydroxylamine were added portionwise (over about 35 minutes) and stirred for a further 2 hours at this temperature.
After dichloroethane was distilled off under reduced pressure, the residue was dissolved in 100 ml of water, and the pH was adjusted to 3 with a 57% aqueous solution of hydroiodic acid. 2,4-dinitrophenol precipitated, but was removed by extraction with ethyl acetate (three times).
The aqueous layer was concentrated and the residue was recrystallized from ethanol to obtain () in 70% yield. In addition, as an aminating agent, O-diphenylphosphinylhydroxylamine (Synthesis, 592
(1982), Tetrahedron Lett., 23 , 3835 (1982))
When using , do almost the same thing, but in this case,
After treatment with hydroiodic acid, diphenylphosphinic acid is recovered by filtration without extraction (more than 90%)
We were able to. (B) Synthesis of 7-acetyl-1-benzyl-2,6-dimethylpyrazolo[1,5-b][1,2,4]triazole (1) N-aminotriazolium iodide () 8g
(0.025mol) in DMF (dimethylformamide) 50
ml, added 40 ml of acetic anhydride, and heated to 120°C. Next, add 12.5 g of sodium acetate and add 12.5 g of sodium acetate.
Stirred at ~130°C for 4 hours. After removing DMF, acetic anhydride, etc. under reduced pressure, it was made basic with a saturated aqueous sodium carbonate solution, extracted with chloroform, the extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off to obtain a brown oil. Ta. This was purified using a silica gel column in a solvent system of n-hexane-ethyl acetate, and 7-acetyl-1-benzyl-
2,6-dimethylpyrazolo[1,5-b][1,
3.2 g (47%) of 2,4] triazole (1) was obtained.
Melting point 105-107℃ Nuclear magnetic resonance spectrum ( _CDCl3 ) δ (ppm): 2.36 (3H, s) 2.43 (3H, s) 2.60
(3H, s) 5.80 (2H, s) 7.0~7.2 (2H) 7.2
~7.36(3H) (C) Synthesis of 1-benzyl-2,6-dimethylpyrazolo[1,5-b][1,2,4]triazole (2) ~ Dissolve 1 to 2 g (7.5 mmol) in 20 ml of ethanol, add 20 ml of concentrated hydrochloric acid, and heat to reflux.
After about 6 hours, the ethanol was removed under reduced pressure, basified with a saturated aqueous solution of sodium bicarbonate, and extracted with ethyl acetate to yield nearly pure deacetylated 1-benzyl-2,6-dimethylpyrazolo[1,5- b]
~1.6 g (95%) of [1,2,4]triazole (2) was obtained. Melting point 87-88℃ Nuclear magnetic resonance spectrum (CDCl ₃ ) δ (ppm): 2.32 (3H, s) 2.44 (3H, s) 5.02
(2H, s) 5.22 (1H, s) 7.10-7.40 (5H) (D) 1H-2,6-dimethylpyrazolo[1,5-
b] Synthesis of [1,2,4]triazole (3) 1-Benzyl-2,6-dimethylpyrazolo[1,5-b][1,2,4]triazole (2) to 1.6
g (7.1 mmol) with about 0.8 g of metallic sodium in liquid ammonia to obtain the desired 1H-2,6
-dimethylpyrazolo[1,5-b][1,2,4]
0.67 g (70%) of triazole (3) was obtained as colorless crystals. Melting point 274-275℃ (decomposition) Mass spectrometry 136 (M ⁺ , 100%) Elemental analysis values C (%) H (%) N (%) Theoretical value 52.93 5.92 41.15 Measured value 52.85 6.02 41.01 Nuclear magnetic resonance spectrum (CDCl ₃ :pyridine-d ₅
= 1:1) δ (ppm): 2.35 (3H, s) 2.43 (3H, s) 5.50
(1H, s) <Example 2> (Synthesis of exemplified compounds 5~) 5 g (16 mmol) of N-aminotriazolium iodide () shown in Example 1, 30 g (79 mmol) of 5 equivalents of lauric anhydride, and 11 g (77 mmol) of tripropylamine were mixed in 100 ml of DMF at 140 to 150°C for about 10 hours. Heated. DMF was removed using an evaporator, ethyl acetate was added, precipitated unreacted lauric anhydride was removed by filtration, and the filtrate was transferred to a separating funnel.
Add 2N aqueous sodium hydroxide solution and shake thoroughly.
The liquid was separated. The aqueous layer was further extracted twice with ethyl acetate, and the ethyl acetate layer was washed with saturated brine.
It was dried over magnesium sulfate, and 30 ml of concentrated hydrochloric acid and 50 ml of ethanol were added to the resulting residue, and the mixture was reduced by heating for about 4 hours, the ethanol was removed, and the mixture was extracted with ethyl acetate. The product was subjected to usual post-treatment and purified using a silica gel column to obtain 0.8 g (14%) of 1-benzyl compound. Nuclear magnetic resonance spectrum ( _CDCl3 ) δ (ppm): 0.88 (3H, brt, J = ~7) 1.30
(20H, brs) 2.40 (3H, s) 2.60 (2H, t,
J=7.5) 5.03 (2H, s) 5.25 (1H, s) 7.10
~7.45 (5H) This 1-benzyl compound was reduced with sodium in liquid ammonia to obtain Exemplified Compound 5~, which is sparingly soluble in organic solvents other than alcohol, in a yield of about 90%. Melting point 154
~155°C <Example 3> (Synthesis of Exemplary Compound 6) 7.2 g (55 mmol) of n-heptanoic acid was dissolved in 15 ml of dimethylformamide (DMF), 7.9 g (55 mmol) of tri-n-propylamine was added thereto, and then 6.1 g (51 mmol) of trimethylacetyl chloride was dissolved in 10 ml of DMF. was added dropwise.
After stirring at room temperature for 10 minutes, 5 g (15.8 mmol) of N-aminotriazolium iodide () and 11.3 g (79 mmol) of tri-n propylamine were gradually added to
℃ and stirred at that temperature for about 5 hours.
After DMF and amine were distilled off under reduced pressure, 100 ml of 2N aqueous sodium hydroxide solution was added, and the mixture was extracted three times with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate. After filtration, it was concentrated under reduced pressure, and the residue was purified by silica gel chromatography.
2.9 g (45%) of (R ₁ =-CH ₃ , [Formula] R ₃ =-C ₆ H ₁₃ ) was obtained. When this was deacylated and debenzylated by the method shown in (C) and (D) of Example 1, 1.0g (68%) of 6-
I was able to get it. Melting point 105-110℃ Nuclear magnetic resonance spectrum (DMSO-d ₆ ) δ (ppm): 0.85 (3H, brt, J = ~7) 1.32
(8H, brs) 2.45 (3H, s) 2.58 (2H, t, J
=7.5) 5.60 (1H, s) <Example 4> (Synthesis of Exemplary Compounds 7~) () 1.0g (3.16mmol) in 8ml of anhydrous DMF
Dissolve 3.6 g of benzoic anhydride in the solution.
(15.8 mmol) and 2.3 g of tri-n-propylamine
(15.8 mmol) was added, and the mixture was heated and stirred at 130°C for 24 hours. After DMF and tri-n-propylamine were distilled off under reduced pressure, 30 ml of ethanol and 10 ml of concentrated hydrochloric acid were added, and the mixture was heated under reflux for 5 days. After removing ethanol and concentrated hydrochloric acid under reduced pressure,
After extraction with ethyl acetate, drying, concentration, and purification by silica gel chromatography, the 1-benzyl compound was obtained.
0.2g (22%) was obtained. Nuclear magnetic resonance spectrum (CDCl ₃ ) δ (ppm): 2.35 (3H, s) 4.95 (2H, s) 5.65
(1H, s) 7.05-7.50 (8H) 7.80 (2H, dd,
J=9.0, 1.5) 0.2 g (0.69 mmol) of the 1-benzyl compound was reduced with 0.05 g of sodium in liquid ammonia to obtain 0.12 g (87%) of the desired 7-. Melting point ~190°C (decomposition) <Example 5> (Synthesis of exemplified compounds 8~, 9~) Add 1.00 g (32 mmol) of () to 15 ml of N-methylpyrrolidone and stir at room temperature. To this, 2.93 g of methoxycarbonylpropionic anhydride and 4.8 ml of tripropylamine were added in order, and the mixture was heated on an oil bath at 130°C. Heated for 3 hours. After cooling, dilute with ethyl acetate,
Washed with water (100ml x 2). The ethyl acetate layer was dried over anhydrous magnesium sulfate, concentrated, and 30 ml of methanol and 20 ml of concentrated hydrochloric acid were added thereto, followed by heating under reflux for 7 hours. After cooling, ethanol was removed by concentration under reduced pressure, and the residue was poured into 100 ml of ice water and neutralized to pH 7.
Extracted with ethyl acetate (50ml x 3). The ethyl acetate layer was dried over anhydrous magnesium sulfate, concentrated, and purified using a silica gel column (20 g).
Obtained 0.16 g (17%) as an oil. Nuclear magnetic resonance spectrum ( _CDCl3 ) δ (ppm): 2.42 (3H, s) 2.60-3.15 (4H, m)
3.63 (3H, s) 5.02 (2H, s) 5.26 (1H, s)
7.12-7.50 (5H, m) Elemental analysis value C (%) H (%) N (%) Theoretical value 64.41 6.08 18.78 Experimental value 64.22 6.30 18.55 This N-benzyl compound was reduced with sodium in the same manner as above to obtain Exemplified Compound 9 ~ could be obtained with a yield of about 80%. Melting point 120-122°C <Example 6> (Exemplary compounds 11-, 12-, 13-,
Synthesis of 14~) 9.5g (30mmol) () and 65g (150mmol)
of 4-(p-nitrophenyl)butyric anhydride and 57 ml
(300mmol) of tripropylamine in 150ml
Dissolved in DMF. The mixture was heated under stirring on a 130°C oil bath for 4 hours, followed by a 140°C oil bath for 2 hours.
The mixture was further heated on an oil bath at 160°C for 6 hours. After DMF was distilled off under reduced pressure, it was dissolved in ethyl acetate, and this ethyl acetate solution was washed with 2N NaOH aqueous solution (2
times). The ethyl acetate layer was dried over anhydrous magnesium sulfate, concentrated, and subjected to silica gel column chromatography (600 g of silica gel, eluent: hexane: ethyl acetate = 2:1 to 1:1).
7.6 g (45%) of () (R ₁ = −CH ₃ ,
[Formula] R ₃ =-(CH ₂ ) ₃ C ₆ H ₄ -NO ₂ ) was obtained. Nuclear magnetic resonance spectrum ( _CDCl3 ) δ (ppm): 2.40 (3H, s) 1.8-3.3 (12H, m)
5.80 (2H, s) 7.0~7.4 (9H, m) 8.1 (4H,
m) 7.6 g (13 mmol) of () was dissolved in a mixed solvent of 150 ml of EtOH and 50 ml of concentrated hydrochloric acid, and heated under reflux for 10 hours. After adding 100 ml of water, ethanol was removed by concentration under reduced pressure. After neutralization with aqueous ammonia, extraction was performed with ethyl acetate, and the ethyl acetate layer was dried over anhydrous magnesium sulfate. After concentration, it was subjected to silica gel column chromatography (140 g of silica gel, eluent: hexane: ethyl acetate = 1:1).
(R ₁ =-CH ₃ , [Formula] R ₃ =- (CH ₂ ) ₃ C ₆ H ₄ NO ₂ ) 3.8 g (76%) was obtained. Nuclear magnetic resonance spectrum (CDCl ₃ ) δ (ppm): 2.03 (2H, m) 2.44 (3H, s) 2.58
~2.85 (4H, m) 5.02 (2H, s) 5.20 (1H,
s) 7.04~7.40 (7H, m) 8.04 (2H, d, J
=8.0) 18g reduced iron in 80ml isopropyl alcohol
(0.32mol), ammonium chloride 1.3g (25mmol)
and 8 ml of water were added, and the mixture was heated with vigorous stirring until it reached reflux. To this was added 0.2 ml of concentrated hydrochloric acid, and the mixture was heated under reflux for 30 minutes. This includes the above nitro body 18.0
g (47.9 mmol) was added little by little over 20 minutes,
The mixture was further heated under reflux for 1 hour. Filter through celite,
Celite was thoroughly washed with ethanol. The filtrate was concentrated, dissolved in ethyl acetate, washed with water, and dried over anhydrous magnesium sulfate. Concentrate to obtain the crude aniline product (R ₃ = -(CH ₂ )
15.8 g (95%) of ₃ C ₆ H ₄ NH ₂ was obtained. Nuclear magnetic resonance spectrum (CDCl ₃ ) δ (ppm): 1.95 (2H, m) 2.38 (3H, s) 2.40
~2.76 (4H, m) 3.36 (2H, br) 4.97 (2H,
s) 5.20 (1H, s) 6.53 (2H, m) 6.91 (2H,
m) 7.00 to 7.38 (5H, m) 15.8 g (45.7 mmol) of this aniline compound was added to 200 ml of liquid ammonia under reflux and stirred. 2.6 g (0.11 mol) of metallic sodium was added little by little to this. Ammonium chloride was added little by little to this, and the mixture was left to stand overnight to remove ammonia. residue
It was dissolved in 2N HC1 aqueous solution and washed with ethyl acetate. The aqueous layer was neutralized with aqueous ammonia, and the precipitate was collected by filtration. The precipitate was washed with water and then with acetonitrile and dried to produce almost pure 117.9.
g (68%). Melting point 199-203℃ Nuclear magnetic resonance spectrum (CDCl ₃ + DMSO-d ₆ ) δ (ppm): 1.88 (2H, br, quintet, J = ~7)
2.41 (3H, s) 2.3~2.8 (4H) 5.42 (1H, s)
6.56 (2H, d, J = 8.5) 6.90 (2H, d, J =
8.5) Mass spectrometry spectrum 255 (M ⁺ , 20%) 136 (100), 119 (90) 106 (50) Infrared absorption spectrum (KBr) 3340, 1605, 1507, 1380, 1270 cm ^-1 11 3.00 g (11.7 mmol) acetonitrile 50ml
In addition to this, N,N-dimethylacetamide 25
ml and heated under stirring until it reached reflux.
In this, acid chloride 7.19 g (12.9 mmol) of acetonitrile solution (20
ml) was added dropwise over 20 minutes, and the mixture was further refluxed for 20 minutes.
Furthermore, an acetonitrile solution (10 ml) containing 0.72 g (0.13 mmol) of the above acid chloride was added dropwise over 10 minutes, and reflux was continued for 30 minutes. After cooling, it was poured into 500 ml of water and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, concentrated, and subjected to silica gel column chromatography (300 g of silica gel, eluent chloroform:methanol = 60:1) to obtain 7.25 g (80%) of 12 (solid). . Elemental analysis values C(%) H(%) N(%) S(%) Theoretical value 69.65 6.88 9.02 4.13 Measured value 68.99 6.90 8.90 4.07 Mass spectrometry (FD) 776 (M ⁺ , bp) Nuclear magnetic resonance spectrum (CDCl ₃ ) δ (ppm): 0.86 (3H, brt, J=7) 1.0 to 2.2
(20H, m) 2.38 (3H, s) 2.5~2.8 (4H, m)
4.68 (1H, brt, J=6) 5.05 (2H, s) 5.45
(1H, s) 6.9~7.4 (13H, m) 7.7~7.9 (4H,
m) 8.17 (1H, s) 11.6 (1H, br) 3.3 g (4.3 mmol) of benzylic compound 12 ~ in THF60
ml and added 0.66 g of 10% Pd/C. This was stirred at 60°C for 3 hours under a hydrogen atmosphere of 60 atmospheres. After cooling, the catalyst was removed by filtration and the filtrate was concentrated. Silica gel column chromatography (silica gel 90g, eluent chloroform: methanol =
1:0~30:1), 2.7g (92%) of 13~
was obtained as a solid. Mass spectrometry (FD) 687 (M ⁺ +2, 50%) 686 (M ⁺ +1,100) 685 (M ⁺ , 30) Add 4.25 g (6.20 mmol) of 13~ and 50 ml of THF to 100 ml of dichloromethane and stir at room temperature. and dissolved. To this was added 795 mg (5.95 mmol) of N-chlorosuccinimide, and the mixture was stirred at room temperature for 15 minutes. After washing with water (150 ml x 2), it was dried over anhydrous magnesium sulfate. After concentration, the residue was subjected to silica gel column chromatography (100 g of silica gel, eluent: chloroform:methanol = 50:1 to 31:1) to obtain 14 to 4.04 g (90%) as a solid. Mass spectrometry (FD) 722, 721, 720 (9:7:9) <Example 7> (Synthesis of exemplified compounds 15~, 16~) 1.79 g (7.00 mmol) of N,N-dimethylamide and 15 ml of N,N-dimethylamide were added to 30 ml of acetonitrile, and the mixture was heated and stirred until it reached a reflux state. Add acid chloride [(t-C ₅ H ₁₁ ) ₂ C ₆ H ₃ OCH (n-C ₄ H ₉ )COCl] to this.
2.83 g (7.70 mmol) of acetonitrile solution (10
ml) was added dropwise over 15 minutes, and reflux was continued for an additional 30 minutes. After cooling, it was poured into 300 ml of water and extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, concentrated, and fractionated using silica gel column chromatography (100 g of silica gel, eluent chloroform:methanol 70:1).
Obtained 3.12 g (76%) as a solid. Elemental analysis value C (%) H (%) N (%) Theoretical value 73.81 8.77 11.95 Measured value 73.64 8.95 11.93 Nuclear magnetic resonance spectrum (CDCl ₃ ) δ (ppm): 0.50-1.00 (7H, m) 1.00-2.16
(26H, m) 2.44 (3H, s) 2.46~2.80 (4H,
m) 4.66 (1H, t, J=6.0) 5.44 (1H, s)
6.90~7.34 (6H, m) 7.64 (1H, d, J=9.0)
7.87 (1H, br, s)

Claims (1)

[Claims] 1. General formula (In the formula, R ₁ represents a hydrogen atom, an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group, R ₂ represents an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group, and X represents an acid group. ) and an N-aminotriazolium salt represented by the general formula (R ₃ CO) ₂ O or [formula] (wherein R ₃ represents a hydrogen atom, an alkyl group, an aryl group, or a substituted aryl group). The general formula (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) 7-acylated pyrazolo [1,5-
b] [1,2,4]triazole was obtained, and the 7-position acyl group of this compound was deacylated to give the general formula (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) Pyrazolo[1,5-b][1,2,
4] Obtain a triazole derivative and reduce the 1-position of this compound to form the general formula (In the formula, R ₁ and R ₃ have the same meanings as above.) A method for producing a pyrazolo[1,5-b][1,2,4]triazole derivative, characterized in that it is a compound represented by the following formula. 2 General formula (In the formula, R ₁ represents a hydrogen atom, an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group, and R ₂ represents an alkyl group, a substituted alkyl group, an aryl group, or a substituted aryl group.) The compound is N-aminated to form the general formula (In the formula, R ₁ and R ₂ have the same meanings as above.
X represents an acid radical. ) to obtain an N-aminotriazolium salt represented by
This N-aminotriazolium salt and an acid anhydride represented by the general formula (R ₃ CO) ₂ O or [formula] (wherein R ₃ represents a hydrogen atom, an alkyl group, an aryl group, or a substituted aryl group) By cyclization condensation, the general formula (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) 7-acylated pyrazolo [1,5-
b] [1,2,4]triazole was obtained, and the 7-position acyl group of this compound was deacylated to give the general formula (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as above.) Pyrazolo[1,5-b][1,2,
4] Obtain a triazole derivative and reduce the 1-position of this compound to form the general formula (In the formula, R ₁ and R ₂ have the same meanings as above.) A method for producing a pyrazolo[1,5-b][1,2,4]triazole derivative, which is characterized by obtaining a compound represented by the following formula.