JPS62273981A - Production of triazolopyrimidineamino derivative - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful in the field of photography and as a physiologically active substance, by reacting a specific triazolo pyrimidine halogen derivative with specific amino compound at a specific temper ature. CONSTITUTION:(A) A triazolopyrimidine halogen derivative expressed by formula I (R1 is H, lower alkyl; R2 is H, 1-8C alkyl, aralkyl, alkenyl or allyl; X is Cl, Br or I), e.g. 2-bromo-4-n-propyl-6-methyl-4, 5-dihydro-triazolo [1,5]pyrimidine, etc., is reacted with an amino compound expressed by the formula R3NH2 (R3 is H, 1-8C alkyl, aralkyl, alkenyl or allyl), preferably at 1: >=1 molar ratio of the former to the latter at 100-300 deg.C, preferably 120-270 deg.C to afford the aimed compound expressed by formula II. The starting material expressed by formula I is a novel substance and obtained by reacting a compound expressed by formula III with a compound expressed by formula IV or V.

Description

Detailed Description of the Invention 3. Detailed Description of the Invention The present invention relates to a method for manufacturing 1811 nitriazolopyrimidine 7mm conductors. In more detail, the tri7zopyrimidine halogen enzyme conductor represented by the following general formula [1] and the first general formula [■I R, N Ru ・・・・・・・・・・・・・・・・・・
・・・・・・・・・7 minified somono and 7 represented by […]
．． Regarding the process for producing the triazolopyrimidine amino enzyme derivative represented by the general formula Lu1l), the reaction is carried out at a temperature in the range of 100 to 300°C. Compounds having a skeleton are useful in the field of photography or as substances that exhibit bioactive activity.
A compound represented by No. 01 Alllictz''1: Hypertrophy is described and is described as being useful as a fog repellent stabilizer for photographic halogenated plate emulsions.

- Mantoku Koko No. 7677/1986 states that tri-7zolopyrimidine conductors are said to be active against bronchial pain, reduce the amount of fat in the body, or have an appetite-reducing effect. It is stated that

It takes N9! Naka@11117 Among them, 7 in Tori 7 Zop mass
Compounds that react with mino ik1;'t4 contain nitrogen atoms in the triazolo and pyrimidine blocks, which poses many difficulties, and therefore complicated synthesis methods are used. The synthesis of a special compound in which a full chloride group is introduced into the pyrimidine mass and a different 7 amino or aminoalkyl group is added to the triazolo salt is referred to as history.

For example, Japanese Patent Publication No. Sho 51-7677 discloses a reverse comparison of the lower grades.

H, N-c=N+cH,>, cH8・h(Br +
<I) CH, N=C=SS-C,H.

↓ S S-C,)1゜↓ C,)i, I b C* ffs Setas ↓ +NH, -NH,・ru0 The present invention provides a method for easily converting the compound represented by the general formula [formula] in 11a. As a result of research into a method for achieving Rm at low cost, we have arrived at the present invention.

1. That is, the present invention is a triazo-pyrimidine/% represented by the following general formula CI) and the following general formula (III R, N).・・・・・・・・・・・・・・・
・・・・・・・・・Triazo ρ pyrimidine 7 represented by the following general formula [formula] characterized by reacting with the 7mino compound represented by (11) at a temperature in the range of 100 to 300°C This is a method for manufacturing a mino sieve conductor.

According to the method of the present invention, Ml'? Despite the presence of R in the general formula C1), it becomes possible to easily substitute a 7-mino group or an alkylamino group instead.

In the method 75 of the present invention, in the tri7zopyrimidine/S Logon rice conductor of the general formula CI) used as a starting material, RI represents a hydrogen atom or a lower alkyl group.

Such alkyl groups may be monobranched or linear, and are generally lower furkyl groups having 5 or less carbon atoms, preferably 4 or less carbon atoms. Examples of such lower alkyl groups are methyl group, ethyl group, n
-propyl MIn-butyl group+n7j crystal.

Further, R7 is a frozen candy atom or a furkyl group having 8 or less carbon atoms,
7ralkyl group, fulkenyl group or allyl group.

The alkyl group may be monobranched or i[chain], and preferably has 5 or less carbon atoms.

Examples of such alkyl groups include methyl group, ethyl group +
N-propyl ik*n-butyl crystals and n-amyl crystals are mentioned.

Further, the fulkenyl group may have at least 8 carbon atoms and at least a double bond, and may be branched.
It may be a chain.

Preferably, the number of translations is 5 or less, and tv is a vinyl group and a 7-lyl group t -Ckl, -C)l=c)i, )
, methallyl group, etc.

hIJ aralkyl group has 8 or less carbon atoms and 1
For example, benzyl group or benzyl group substituted with rogen, hydroxyl group, methoxy group, etc. can be mentioned.

In addition, the allyl group is a phenyl group or a methyl group 9
Examples include a methoxy group, a phenyl group substituted with a water group, a cyano group, and a 1,000-methyl group.

Furthermore, in the general formula [1], X is a chlorine atom.

Bromine atom! However, from an economic point of view, a strongyle atom or a bromine atom is preferred. Compound 9J of the general formula (l), which is the starting material, is novel to the best of the inventor's knowledge. It is a substance.

It can be manufactured in various ways. One way to do this is to fertilize the unexploited soil first.

That is, the following general formula [VI
) or (Vl-b) n alkoxy device 11
At least 1 g selected from the group consisting of 17 krylic spun conductor, an aqueous alkali metal, charcoal salt, and 7 methane.
Salt j! In the presence of I catalyst, an aprotic polar solvent.

By reacting at a temperature of -20 DEG to 350 DEG C., a tri-7zolobyrimidine/10-gon derivative represented by the following general formula [■■] can be obtained. However, the method for producing the starting material is not limited to these methods.

As the other 10,000 starting materials required in the present invention, an amine compound represented by the following general formula (113% formula %) is used, where R1
A hydrogen atom, a fulkyl group having carbon a8 or less, a 7ralkyl group, an alkenyl group, or a 7lyl group is used.

The furkyl group may be monobranched or linear, and preferably has 5 or less carbon atoms. Examples of alkyl groups include methyl group, ethyl group, n
-propyl group, n-butyl group + n 7 mil group are removed.

In addition, the alkenyl group may have less than or equal to 2 carbon atoms and may be branched.
! It may be a chain.

Preferably, it has an envy of less than $ia5, such as a vinyl group, a 7-aryl group (-〇M, -1=CH1), a methallyl group, and the like.

As the aralkyl group in I, the number of carbon atoms is 8 or less, for example, a benzyl group or a benzyl group in which a hydroxyl group, a methoxy group, etc. are added.

Examples of the Ik87 lyl group include a phenyl group, or a phenyl group substituted with a methyl group, a methoxy group, a nitrogen group, a water NNi, a cyano group, a thiomethyl group, and the general formula (111). ) in (・te

# indicates a p atom or an iodine atom, or a chlorine atom or a dioxygen atom is preferred from an economical point of view.

The smell of the method of the present invention? , amine compound (111) for starting material (1) is generally reactive
There is no particular limitation as long as the starting material [131 moles] may be less than 1 mole or more than 1 mole. However, in general, 1 mole or more is preferred. Although the upper limit is not generally limited, it is self-limited for economic reasons.

The reaction in the method of the present invention is preferably carried out in a solvent, in which case the reaction is carried out in a bath.

It is preferable to use a nitrogen-containing compound with a 5-membered ring or a 6-membered ring. Among them, aromatic compounds are particularly used in the case of shoulder dogs. Examples of these include the following.

Pyrrole pyrazole imidazole 1,
2.3-) Su7zole 1.2.4-) Su7zolepyridine Pyrazine Pyridazine Virimidine ovwyy Pyrazine' Cinnoline Phthalazine These 11! #Sada is 0.1 to 1 with respect to Lllllfi part of trifzolopyhemidine 8logone derivative which is the starting material.
0001 parts by weight, preferably in the range of 0.5 to 500 parts by weight.

In carrying out the method of the present invention, the reaction temperature is 100°C for one batch.
~300°C, preferably 110°C ~ 280°C, sometimes preferred 1
1. < is 120°C to 270°C. If the reaction temperature is lower than the above range, it is difficult for the reaction to occur, and if the reaction temperature is higher than this range, the formation of by-products and the fraction M of the product will occur, so in the reaction of the present invention, which is not preferable, , the reaction time is relatively short at high reaction temperatures in the above range of reaction temperatures, and relatively long at low reaction temperatures.In general, the reaction time is 1.
minutes to 1 (10 hours, preferably 5 minutes to 50 hours).

For example, at a reaction temperature of about 220 DEG C., most of the compounds reach the bottom in 1 to 2 hours.

The reaction of the present invention is carried out under normal pressure or elevated pressure. Further, the reaction can be carried out in either a bunch type, a wire type, or a combination thereof.

By the above method, the desired tri-7zoropyrimidine amino conductor can be easily obtained in a striped manner.

The unexploded 1811 will be explained in detail below, with all its false claims.

Example 1 2-amino-4-n-propyl-6-methyl-4,5-
Synthesis of dihydro-tri-7zolo(1,5)pyrimidine: Contents: 2-bromo-4-n-bouvyl-6-methyl-4 as starting material in a 100V titanium autoclave.
,5-dihydro-triazolo L],5]hyrimidine CI
) 0.50y, prepare 30th N-methylpyrrolidone ii! After elementary substitution, ammonia was introduced. 220℃
, the total pressure in the autoclave after 3 hours of reaction was 9.
It was okt, /cs%. Analysis of the crystals by gas chromatography showed a conversion of 424% and a selectivity of 909.

After cooling, 1q-methylpyrrolid/ was removed from the taken out reaction solution under reduced pressure. Add 51L of water to the remaining dark purple residue.
The temperature was increased to 70° C. and the aqueous phase was decanted.

After water was removed under reduced pressure and dried, 168 crystals were obtained.21 When recrystallized with ethanol, 2-7 minnows and 4-
n-propyl-6-methyl-4,5-dihydro-8-
) Crystals of 7zo(1,5-a)pyrimidine were obtained.

implementation? 112-5 Omaji Comparative Examples 1-3 Using a σ titanium autoclave as in Example 1, 2-brom-4-1-enelopyl-6-methyl-4,5-dihydro-triazolo(1,5 ) Pyrimidine and 30 different AT baths were charged, ammonia was introduced, and a reaction was carried out.

The target object is Shimajin water-based flame gas chromatography GC.
-7A' was analyzed under the following conditions, and the results are shown in Table 1.

Analytical Conditions Examples 6 to 12 Using the starting materials shown in Table 2 below, reactions were carried out under the 4 reaction conditions shown in Oka Table. The results are shown in Table 2. Also, Table 3 In addition, the homopod theta ttf of each of the seven zorohyrimidine amino #s2J! bodies obtained according to the present invention is shown.

Straw 3 tables - 1ll I R+1 Measured by Nugo/method.

NMR was performed using CL) C/, and DMSO as the solvent.

3rd & -+2+

Claims (1)

[Claims] 1. The following general formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼...[I] [However, in the formula, R_1 represents a hydrogen atom or a lower alkyl group, and R_2 represents a hydrogen atom or the number of carbon atoms. It represents an alkyl group, aralkyl group, alkenyl group or allyl group of 8 or less, and X represents a chlorine atom, a bromine atom or an iodine atom. ] A triazolopyrimidine halogen derivative represented by the following general formula [II] R_3NH_2...[II] [However, R_3 represents a hydrogen atom or an alkyl group having 8 or less carbon atoms, an aralkyl group, an alkenyl group, or an allyl group. ] The following general formula [III] is characterized by reacting with an amino compound represented by the following at a temperature in the range of 100 to 300°C. ▲There are mathematical formulas, chemical formulas, tables, etc.▼...[III] The definitions of R_1, R_2 and R_3 are the same as above. ] A method for producing a triazolopyrimidine amino derivative represented by: 2. The production method according to item 1, wherein the reaction is carried out in a 5-membered ring or 6-membered ring nitrogen-containing compound solvent.