JPS5857437B2 - Synkinatieno (3,4-D) Pyrimidinedione - Google Patents

Description

Detailed Description of the Invention The present invention is based on the general formula (1) (wherein R1 is a phenyl group or a phenyl group substituted with a trifluoromethyl group, R2 is (a) a lower alkyl group, middle) lower alkyl group substituted with lower alkoxy group, hydroxyl group, halogen atom, lower cycloalkyl group, lower alkylamino group or phenyl group, (・
The present invention relates to a method for producing a novel cheno[3,4-d]pyrimidinedione derivative represented by υ alkenyl group or (ni)alkynyl group.

More specifically, the compound represented by the general formula (U) (wherein R1 has the same meaning as above) is combined with the general formula (E) (wherein R2 has the same meaning as above, and X is a halogen atom and The present invention relates to a method for producing a compound represented by the general formula (I) by reacting a compound represented by an organic sulfonic acid or an inorganic acid ester group.

R1 and R2 in the above general formulas (I) and (II) and
To explain more specifically about and Substituted lower alkyl groups include lower alkyl groups such as methyl, ethyl, globil, inglovir, n-butyl, inobutyl, and n-pentyl, lower alkoxy groups such as methoxy and ethoxy, hydroxyl groups, chlorine, bromine, fluorine, iodine, etc. ... rogen atom, lower cycloalkyl group such as cycloglopyl, dimethylamino,
A substituted lower alkyl group substituted with a lower alkylamino group such as diethylamino or a phenyl group, an alkenyl group such as allyl, 3-methylallyl, 3,3-dimethylallyl, and the like, and an alkynyl group such as glopargyl.

In addition, the organic sulfonic acid ester group of
Examples of the inorganic acid ester group include ester groups of alkyl sulfonic acids such as benzyl sulfonic acid, and ester groups of inorganic acids such as sulfuric acid, phosphoric acid, and nitric acid.

The compound of general formula (II) which is the starting material of the present invention is 3-
It can be obtained in good yield by ring-closing the 7minor 4-carbamoylthiophene derivative with diethyl carbonate in the presence of sodium ethylate.

The reaction formula of the present invention is as follows.

The reaction in the present invention is dimethylformamide, hexamethylphosphoramide, tetrahydrofuran, benzene,
Metal compounds such as sodium hydride, sodium amide, sodium alcoholade, etc. in organic solvents such as dioxane,
It is preferable to carry out the reaction in the presence of an organic base such as pyridine or trialkylamine, or an inorganic base such as an alkali hydroxide or an alkali carbonate. Particularly when the above-mentioned metal compounds are used, the target compound can be obtained in an extremely good yield.

The reaction temperature is not particularly limited and may be room temperature, but the reaction proceeds in a short time when heated.

The compound obtained by the present invention is a new compound that has not been described in any literature, and has pharmacological effects such as remarkable anti-inflammatory effect, analgesic effect, and central nervous system depressing effect, and is an industrially useful compound as a pharmaceutical.

EXAMPLES The present invention will be explained in more detail with reference to Examples below.

Example 1 ■-Phenylcheno[3.4-d,lpyrimidine-2.
After dissolving 2.4 parts of 4(IH·3H)-dione in 20 ml of dimethylformamide, 0.1' of about 50% sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes.

Next, ethyl iodide 312 was added and reacted at room temperature for 1.5 hours.

After the reaction, the solvent was distilled off under reduced pressure, water was added to the residue, and the precipitated crystals were recrystallized from ether to give pale yellow prismatic crystals of 1-phenyl-3-ethylcheno[3,4-d]pyrimidine-2.・4(IH・3H)-dione 2.3y' was obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 144-145℃ Elemental analysis value C14H12N202 S Theoretical value C: 61.76 H: 4.44 N: 10
．． 29 actual measurement value C: 61.65 H: 4.48 N
:10.21 Example 2], -(m=chlorophenyl)cheno[3.4-d'
About 50% sodium hydride (0.6 f) was added to a solution of 2.81 liters of pyrimidine-2.4(IH.3H)-dione and 20 TrLl of dimethylformamide, and the mixture was stirred at room temperature for 30 minutes.

Next, it was heated to 70°C and p-1 luenesulfonic acid-n-7"
Lopylester 6.4f with dimethylformamide 151
A solution dissolved in nl was added dropwise, and the mixture was reacted at 70°C for 3 hours.

After the reaction, the solvent was distilled off under reduced pressure, and the residue was recrystallized from ether to give colorless needle-like crystals of 1-(m-chlorophenyl)-3-n-propylcheno[3.4-d]pyrimidine 7.
-2-4(IH-3H)-di,ton 2.1f was obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 132-133℃ Elemental analysis value C1, H13CIN202S theoretical value C:
56.16 H: 4.08 N: 8.73 Actual value
C: 56.09 H: 4.09 N: 8.74 Example 3 1-(m-fluorophenyl)cheno[3.4-d)pyrimidine-2.4(]H.3H)-dione 2.6P About 50% sodium hydride (0.6 P) was added to a solution of dimethylformamide and dimethylformamide (25 Tll), and after stirring at room temperature for 30 minutes, 2.3 l of methyl fluorosulfate was added and allowed to react at room temperature for 1 hour.

After the reaction, the solvent was distilled off under reduced pressure, water was added to the residue, and the precipitated crystals were recrystallized from chloroform to give pale yellow prism crystals 1-(m-fluorophenyl)-3-methylcheno[3,4- d] pyrimidine-2.4(IH.3H)-dione 2.51 was obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 226-228°C Elemental analysis value C13H9FN202 S Theoretical value C: 56.51 H: 3.28 N: 10
．． 14 Actual measurement value C: 56.48 H: 3.21 N
:10.18 Example 4 1-(m-toIJfluoromethylphenyl)cheno[3
・4-d] Approximately 50% sodium hydride (0.07 P) was added to a solution of 0.5 liters of pyrimidine-2,4(IH・3H)-dione and 25 ml of dimethylformamide at room temperature.
After stirring for 0 minutes, dimethyl sulfide [) and 53P were added, and the mixture was stirred at room temperature for 3 hours.

After the reaction, the solvent was distilled off under reduced pressure, water was added to the residue, and the precipitated crystals were recrystallized from ether to obtain colorless needle crystals.
-(m-)Lifluoromethylphenyl)-3-methylcheno[3.4-d)pyrimidine-2.4(IH.3H)
-Dione 0.38P was obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 177-178°C Elemental analysis value C14H9F3N202S Theoretical value C: 51.53 H: 2.78 N: 8.
58 actual measurement value C: 51.42 H: 2.80 N:
8.56 Example 5 1-(m-fluorophenyl)cheno[3.4-d)
To a solution of 2.6 ml of pyrimidine-2.4(IH.3H)-dione and 30 ml of dimethylformamide was added 4.2 P of trimethyl phosphate, and the mixture was reacted under reflux for 5 hours.

After the reaction was completed, the solvent was distilled off under reduced pressure, and the residue was recrystallized from chloroform to give 1-(m-fluorophenyl)-3-methylcheno[3.4-d]pyrimidine-2. 2.41 of 4(IH·3H)-dione was obtained.

The melting point of this material was 226-228°C.

Example 6 1-(m-trifluoromethylphenyl)cheno[3.
4-d]pyrimidine-2.4(IH.3H)-dione 3
．． 1′? was dissolved in 25 ml of dimethylformamide, 0.61 ml of about 50% sodium hydride was added, and the mixture was stirred at room temperature for 30 minutes.

Next, 3.71 g of cyclopropylmethylbromide was added and reacted at room temperature for 1 hour.

After the reaction, the solvent was distilled off under reduced pressure, the residue was extracted with ether, and after dehydration, it was adsorbed on a column packed with silica gel and developed with ether.The solvent in the first eluate was distilled off, and the residue was extracted with ether. and petroleum ether to give colorless needle-like crystals of 1-(m-t')fluoromethylphenyl).
-3-cyclopropylmethylcheno[3.4-d)pyrimidine to give 2.4(IH.3H)-dione 3.21.

The melting point and elemental analysis values of this substance were as follows.

Melting point 135-136℃ Elemental analysis value C17HI3F3N202 S theoretical value C
: 55.74 H: 3.57 N: 7.65 Actual value C: 56.05 H: 3.57 N near, 7
5 Examples 7-24 According to the methods of Examples 1-6, the compounds shown in the following table were synthesized in good yields.

Claims (1)

[Scope of Claims] 1 A compound represented by the general formula (wherein R1 means a phenyl group substituted with (a) a phenyl group, a (b) halogen atom, or a trifluoromethyl group) has a compound represented by the general formula (the formula In the formula, R2 is (a) a lower alkyl group, middle) a lower alkoxy group, a hydroxyl group, a lower alkyl group substituted with a rogen atom, a lower cycloalkyl group, a lower alkylamino group, or a phenyl group, a 0→alkenyl group, or ) an alkynyl group, X means a halogen atom and an ester group of an organic sulfonic acid or an inorganic acid. A method for producing a novel cheno[3,4-d]pyrimidinedione derivative represented by